HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fantini, M. C. Articles by Neurath, M. F. Search for Related Content PubMed PubMed Citation Articles by Fantini, M. C. Articles by Neurath, M. F.

Cutting Edge: TGF- Induces a Regulatory Phenotype in CD4⁺CD25^– T Cells through Foxp3 Induction and Down-Regulation of Smad7

Massimo C. Fantini^*, Christoph Becker^*, Giovanni Monteleone, Francesco Pallone, Peter R. Galle^* and Markus F. Neurath^1,*

^* Laboratory of Immunology, I. Medical Clinic, Johannes Gutenberg University of Mainz, Mainz, Germany; and Department of Internal Medicine, University of Rome Tor Vergata, Rome, Italy

	Abstract

Top Abstract Introduction Materials and Methods Results Discussion References

 
CD4⁺CD25⁺ regulatory cells are a subpopulation of T lymphocytes of thymic origin. However, recent data suggest an alternative commitment of regulatory T cells in the periphery, although the precise mechanism is unknown. In the present work, we demonstrate that TGF- is able to induce Foxp3 expression and subsequently a regulatory phenotype in CD4⁺CD25^– peripheral murine T cells. Similarly, TGF- induced Foxp3 in human CD4⁺CD25^– T cells. Moreover, we show that the inhibitory Smad7 protein that is normally induced by TGF- and limits TGF- signaling, is strongly down-regulated by Foxp3 at the transcriptional level. Foxp3-mediated down-regulation of Smad7 subsequently rendered CD4⁺CD25^– T cells highly susceptible to the morphogenic and regulatory effects of TGF- signaling via Smad3/4. In summary, we demonstrate that TGF- induces a regulatory phenotype in CD4⁺CD25^– T cells through the induction of Foxp3 and a positive autoregulatory loop of TGF- signaling due to the absence of Smad7.

	Introduction

Top Abstract Introduction Materials and Methods Results Discussion References

 
Immunological tolerance is a key feature of the immune system and allows the organism to discriminate between self and nonself. Such tolerance is achieved by processes occurring both during the development of the immune system in the thymus (central tolerance) and the lifespan of lymphocytes in the periphery (peripheral tolerance) (1, 2). Peripheral tolerance is required to inhibit reactive T cell clones escaped from thymic selection or originated de novo against self Ags. In this context, a group of specialized T regulatory cells expressing CD25 plays a key functional role (3, 4, 5). Recent evidence suggests that naturally occurring CD4⁺CD25⁺ regulatory T cells are characterized by the exclusive expression of the winged-helix/forkhead transcription factor Foxp3 (4, 5, 6). Although the thymic origin of CD4⁺CD25⁺ T cells has been demonstrated, several findings suggest that such cells may also be generated in the periphery by an unknown mechanism. In the present report, we provide evidence that TGF- is able to induce Foxp3 expression in CD4⁺CD25^– T cells and promotes the acquisition of regulatory properties in these cells.

	Materials and Methods

Top Abstract Introduction Materials and Methods Results Discussion References

 
Reagents and media

Anti-mouse CD3 (145-2C11), anti-mouse CD28 (37.51), anti-human CD3, anti-human CD28 (CD28.2; BD Biosciences, Mountain View, CA), human rTGF-1 (Strathmann Biotech, Hamburg, Germany), human purified TGF- (R&D Systems, Minneapolis, MN), X-Vivo15 (BioWhittaker, Heidelberg, Germany), neutralizing anti-TGF- Abs (I. Fuss, Mucosal Immunology Section, National Institutes of Health, Bethesda, MD), and HepG2 cells (American Type Culture Collection, Manassas, VA) were cultured in complete RPMI 1640 (7).

Cell lines and plasmid

Smad7 promoter reporter pS7-5 was a gift of E. P. Böttinger (Department of Medicine and Molecular Genetics, Albert Einstein College of Medicine, Bronx, NY), Foxp3 expression vector was kindly provided by M. Stassen (Institute of Immunology, Mainz, Germany). pMACS K^k.II vector was purchased from Miltenyi Biotec (Bergisch-Gladbach, Germany); -galactosidase (-gal)² expression vector was purchased from Invitrogen (Heidelberg, Germany).

Isolation of primary T cells

Murine spleen T cells were isolated by MACS (Miltenyi Biotec) (7). CD4⁺CD25⁺ and CD4⁺CD25^– T cells were sorted from CD4⁺ splenocytes using the CD4⁺CD25⁺ Regulatory T cell Isolation kit (Miltenyi Biotec). Human T cells were isolated from buffy coats using CD4-MACS Multisort beads or CD4-MACS negative selection followed by CD25-MACS positive selection (Miltenyi Biotec). Cells were >93% pure, as determined by FACS analysis.

Flow cytometric analysis

Cells were resuspended in PBS 0.5% BSA. For staining, anti-mouse CD25 PE (Caltag Laboratories, Hamburg, Germany) and anti-mouse CD4 FITC (BD PharMingen, San Diego, CA) were used. Stained cells were analyzed by FACScan (BD Biosciences).

T cell proliferation

T cell proliferation was determined using the 5-bromo-2-deoxyuridin (BrdU)-based Cell Proliferation ELISA (Roche, Heidelberg, Germany).

RT-PCR

Reverse transcription into complementary DNA was performed using the Moloney murine leukemia virus reverse transcriptase (Invitrogen, San Diego, CA). PCR was performed using the RedTaq PCR reagents (Sigma-Aldrich, St. Louis, MO) and the following primers: human Foxp3, 5'-ATG CCT CCT CTT CTT CCT TGA-3' and 5'-ATT GTG CCC TGC CCT TCT CA-3'; murine Foxp3, 5'-GGC GAA AGT GGC AGA GAG GTA T-3' and 5'-AAG ACC CCA GTG GCA GCA GAA-3'; murine IL-2, 5'-ATT GAC ACT TGT GCT CCT TGT C-3' and 5'-TTG ACA GAA AGG CTA TCC ATC-3'; murine TGF-, 5'-TGC TGC TTT CTC CCT CAA CCT-3' and 5'-CAC TGC TTC CCG AAT GTC TGA-3'; human Smad7, 5'-TCA CCT TAG CCG ACT CTG C-3' and 5'-ACA CCC ACA CAC CAT CCA C-3'; -actin, 5'-TGA CGG GGT CAC CCA CAC TGT GCC CAT CTA-3' and 5'-CTA GAA GCA TTT GCG GTG GAC GAT GGA GGG-3'. PCR products were analyzed on 1% agarose gels.

Transient transfections and reporter gene analysis

Foxp3 expression vector (2.5 µg) along with 2.5 µg of the pMACS K^k.II vector were transfected into 5 x 10⁶ cells using the AMAXA Human T Cell Nucleofector kit (Cologne, Germany). In addition, 0.1 µg of Foxp3 expression vector or pCDNA3.1 empty plasmid, 0.1 µg of -gal reporter gene, and 1 µg of pS7-5 Smad7 promoter reporter gene were transfected in 80–90% confluent HepG2 cells in a 24-well plate using Lipofectamine Plus Reagent (Invitrogen,). Luciferase activity was measured with a standard luminometer (Sirius, Berthold, Pforzheim, Germany). Luciferase activity was normalized to the -gal expression and to the protein content of the sample.

ELISA

IL-10, IL-4, and IFN- were measured by commercially available ELISA (BD PharMingen for IL-10 and IL-4, R&D Systems for IFN-). In some experiments, serum-free medium in the presence or absence of TGF- was used.

Western blotting

For human and murine Foxp3 analysis, T cell extracts were analyzed by Western blotting (7). Rabbit anti-mouse Foxp3 (1 µg/ml; E. Schmitt, Institute of Immunology, Mainz, Germany) or goat anti-human Foxp3 (Abcam, Cambridge, U.K.) and 1:1000 HRP-labeled anti-rabbit or anti-goat IgG (DAKO, Hamburg, Germany) and the ECL system (Amersham, Arlington Heights, IL) were used.

	Results

Top Abstract Introduction Materials and Methods Results Discussion References

 
TGF- induces Foxp3 expression in CD4⁺ T cells

Previous studies have demonstrated a pivotal role of TGF- in mediating immunological tolerance (8, 9). Therefore, we tested the possibility that TGF-1 might regulate Foxp3 expression in murine and human CD4⁺ T cells. Accordingly, we stimulated purified splenic CD4⁺ T cells from FVB mice in the presence or absence of TGF-. CD4⁺ T cells were activated with anti-CD3 and anti-CD28 Abs in serum-free medium for 5 days and Foxp3 expression was analyzed by RT-PCR (Fig. 1A). It was found that TGF- induced Foxp3 expression, whereas cells cultured in the absence of TGF- showed reduced or no expression of Foxp3. Thus, TGF- emerges as an important factor for the induction of Foxp3 expression in murine CD4⁺ T cells. Similarly, TGF- stimulation regulated Foxp3 expression in anti-CD3/CD28-stimulated human CD4⁺ T lymphocytes at the mRNA and protein level, suggesting that TGF- controls expression of this key regulatory protein both in human and murine T cells (Fig. 1, B and C).

View larger version (32K): [in this window] [in a new window]   FIGURE 1. TGF-1 regulates Foxp3 expression. A, Murine CD4+ T cells were cultured with anti-CD3/CD28 Abs in serum-free medium for 5 days in presence or absence of 1 ng/ml TGF-1. Foxp3 levels were determined by RT-PCR at indicated time points. B and C, Western blotting (B) and PCR analysis (C) for Foxp3 expression in human CD4+ T cells stimulated in the presence or absence of TGF-1.

TGF- induces Foxp3 in CD4⁺CD25^– but not CD4⁺CD25⁺ T cells

To determine the subpopulation of CD4⁺ T cells in which Foxp3 expression is regulated by TGF-, murine and human CD4⁺ T lymphocytes were separated into CD25⁺ and CD25^– fractions. As shown in Fig. 2, A and B, TGF- stimulation had little or no effects on Foxp3 expression in the murine CD4⁺CD25⁺ T cell subset. In contrast, a strong induction of Foxp3 expression was observed in CD4⁺CD25^– T cells after 24–120 h of culture in the presence of TGF-, although TGF- suppressed the proliferation of these cells (Fig. 2C). These data were confirmed by Western blot analysis (Fig. 2D) and extended by the observation that TGF--dependent Foxp3 induction required stimulation with anti-CD3/28 Abs (Fig. 2E). Similarly to murine T cells, TGF- stimulation induced the expression of Foxp3 in human CD4⁺CD25^– T cells after 5 days of cell culture (Fig. 2F). Taken together, these data suggest that TGF- controls the generation of Foxp3⁺ T cells from CD4⁺CD25^– precursor cells in mice and humans.

View larger version (30K): [in this window] [in a new window]   FIGURE 2. TGF- induces Foxp3 expression in murine CD4+CD25– but not CD4+CD25+ T cells. T cells were cultured for 5 days in presence or absence of TGF-1 as above. Cells were collected at the indicated points and Foxp3 levels were analyzed by RT-PCR (A and B) or Western blots (D). One representative experiment of three is shown. Stimulation of murine T cell subsets with TGF- suppressed anti-CD3/CD28-induced T cell proliferation, as shown by a BrdU-based assay. T cells were cultured in the presence (TGF-+) or absence (TGF-–) of rTGF- for 5 days as above (C). TGF--dependent induction of Foxp3 expression required stimulation with anti-CD3/CD28 Abs, as shown by RT-PCR (E). In addition, stimulation of human CD4+CD25– T cells with TGF- resulted in the induction of Foxp3 (F). Human T cells were isolated (14 ) and cultured for 5 days in the presence or absence of TGF- and anti-CD3/CD28 Abs, as indicated. Foxp3 levels were determined by RT-PCR. P1 = patient 1; P2 = patient 2.

TGF--induced Foxp3⁺ T cells express TGF-

We next investigated the production of regulatory cytokines by TGF--stimulated CD4⁺CD25^– T cells. CD4⁺CD25^– T cells cultured in the presence of TGF- showed lower expression of IL-10 than cells activated in the absence of TGF- (Fig. 3A). In addition, the former cells produced little or no proinflammatory cytokines such as IL-4 and IFN- in cell culture. Finally, we observed that CD4⁺CD25^– T cells stimulated with TGF- contained higher levels of TGF- mRNA than cells cultured in the absence of TGF- (Fig. 3A). Taken together, these findings indicate that TGF- stimulated CD4⁺CD25^– T cells acquire a cytokine profile consistent with that described for regulatory CD4⁺CD25⁺ T lymphocytes (10). Furthermore, CD4⁺CD25^– T cells cultured in the presence of TGF- expressed CD25 at day 5 but not day 0, as demonstrated by FACS analysis (Fig. 3B).

View larger version (33K): [in this window] [in a new window]   FIGURE 3. Supernatants from the above murine experiments (Fig. 2) were assayed for cytokine content by ELISA (A). TGF-1 expression was assayed by RT-PCR to avoid any potential contamination by rTGF-. TGF--stimulated CD4+CD25– cells contained TGF- mRNA but produced low levels of IL-10 and little or no IFN- and IL-4. Mean values ± SD from three independent experiments are shown. B, Analysis of CD25 expression by FACS analysis. CD4+CD25– T cells were cultured for indicated periods of time in the presence of TGF- before FACS analysis. Thirty percent of T cells cultured in the absence of TGF- for 5 days expressed CD25 probably due to T cell activation by anti-CD3 plus anti-CD28 Abs (data not shown).

View larger version (20K): [in this window] [in a new window]   FIGURE 4. A, Foxp3+ cells generated from TGF--stimulated CD4+CD25– cells suppress T cell proliferation. Murine CD4+CD25– T cells were activated in the presence or absence of TGF-1 for 5 days as above, extensively washed, and cocultured with freshly isolated CD4+ T cells. After 5 days, cells were pulsed with BrdU and 16 h later were assayed for BrdU incorporation. TGF--stimulated CD4+CD25– cells significantly suppressed CD4+ T cell proliferation as compared with T cells cultured in the absence of TGF- (p < 0.05). Data represent mean values ± SD from three independent experiments. B, Partial inhibition of the suppressive effect of TGF- stimulated CD4+ T cells by neutralizing anti-TGF--Abs. T cells were cultured as above in the presence or absence of anti-TGF--Abs followed by analysis of BrdU incorporation.

Foxp3 expression allows TGF- signaling through down-regulation of Smad7

Finally, we analyzed TGF- signaling via Smad proteins in Foxp3-expressing CD4⁺CD25^– T lymphocytes. First, we determined potential effects of Foxp3 on expression of the inhibitory Smad7 protein. Accordingly, primary CD4⁺ T cells were transfected with a Foxp3 expression vector in the presence or absence of TGF-. Positively transfected cells were then selected using cotransfection of the pMACS K^k.II vector resulting in a sorted cell population with 95% transfection efficacy. Analysis of Smad7 mRNA levels showed Smad7 induction upon TGF- stimulation in control-transfected cells while overexpression of Foxp3 completely abrogated TGF--induced Smad7 expression in CD4⁺ T cells (Fig. 5A).

View larger version (32K): [in this window] [in a new window]   FIGURE 5. A, Human CD4+ T cells were cotransfected with a Foxp3 expression vector or an empty control vector and the pMACS Kk.II expression vector. Twenty-four hours later, transfection cells were sorted for the expression of H-2Kk and starved for 16 h in serum-free medium. TGF-1 (4 ng/ml) was added for 60 min, as indicated, before Smad7 expression was analyzed by RT-PCR. TGF- stimulation led to induction of Smad7 levels in T cells, while forced Foxp3 expression suppressed Smad7 levels. B, HepG2 cells were transiently cotransfected with a Foxp3 expression vector or an empty control vector, along with the pS7-5 Smad7 promoter reporter gene and a -gal expression vector. After transfection, cells were starved for 12 h before stimulation with TGF- for an additional 10 h. Cell lysates were assayed for luciferase activity. Data represent mean values ± SD from four independent experiments. C, CD4+ T cells were cotransfected with a Foxp3 expression vector or an empty control vector and a vector containing a Smad3/4 response element upstream of the luciferase gene. Foxp3 expression induced up-regulation of the Smad3/4 response element. Data represent mean values ± SD from three independent experiments.

	Discussion

Top Abstract Introduction Materials and Methods Results Discussion References

 
Although the thymic origin of CD4⁺CD25⁺ T cells has been demonstrated, several findings suggest that such cells may also be generated from CD25^– precursor cells in the periphery (11, 12). In the present study, we have found that TGF--mediated induction of Foxp3 in CD4⁺ CD25^– T cells results in the development of T cells with regulatory functions.

TGF- regulated Foxp3 expression in both murine and human CD25^– CD4⁺ T cells, while it had little or no effects on Foxp3 expression in CD25⁺CD4⁺ T cells. TGF--induced Foxp3⁺ T cells, generated from CD4⁺CD25^– precursor T cells, showed increased expression of TGF- and low IL-10 production but failed to produce proinflammatory cytokines such as IFN- and IL-4, consistent with the cytokine profile of naturally occurring CD4⁺CD25⁺ cells (10). Moreover, TGF--stimulated CD25^– CD4⁺ T cells showed regulatory potential in a coculture system with activated naive T cells, suggesting that TGF- induces regulatory T cells from a CD25^– T cell population. Importantly, the induction of Foxp3 by TGF- required stimulation via the TCR suggesting that Ag-specific activation is required to induce such regulatory T cell responses.

Subsequent studies showed that TGF--induced Foxp3 down-regulates Smad7 expression in CD4⁺ T cells and thereby suppresses the expression of the key negative regulator of TGF- signaling. This effect of Foxp3 on Smad7 expression was mediated by a direct effect of Foxp3 on Smad7 promoter activity. Taken together, these data suggest a model in which TGF- plays a pivotal role in the generation of regulatory T cells from a population of peripheral CD4⁺CD25^– T cells through the induction of the key transcription factor Foxp3. Foxp3 enhances the TGF- effects in these cells by down-regulation of Smad7 thereby creating a positive autoregulatory loop of TGF- signaling in CD4⁺CD25^– T cells that potentially stabilizes their regulatory phenotype. However, Piccirillo et al. (13) showed that CD4⁺CD25⁺ T cells isolated from TGF-^–/– mice during the first 3–7 days after birth show normal regulatory function. Taken together, these data suggest a dispensable role of TGF- in mediating CD4⁺CD25⁺ regulatory function, but underline a new role for TGF- in the maintenance of the regulatory compartment in the periphery via its effects on CD4⁺CD25^– T cells. Consistent with such role in peripheral tolerance, TGF-^–/– mice have been shown to develop an autoimmune response with loss of tolerance and multiorgan inflammation within several weeks after birth (8).

The data from the present study suggest a pivotal role for TGF- in the generation of Foxp3⁺ regulatory T cells in the periphery via TGF- mediated induction of Foxp3 in CD4⁺CD25^– T cells. Foxp3 in turn down-regulates Smad7 and renders T cells highly susceptible to the morphogenic and regulatory effects of TGF- signaling via Smad3/4. The concept that regulatory T cells can be generated in vitro from the large pool of CD4⁺CD25^– naive T cells via TGF- could open the way toward new therapeutic approaches for autoimmune and allergic diseases based on modulation of TGF- and Foxp3 expression.

	Footnotes

 
¹ Address correspondence and reprint requests to Dr. Markus F. Neurath, Laboratory of Immunology, I. Medical Clinic, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, 55131 Mainz, Germany. E-mail address: neurath{at}1-med.klinik.uni-mainz.de

² Abbreviations used in this paper: -gal, -galactosidase; BrdU, 5-bromo-2-deoxyuridin.

Received for publication December 8, 2003. Accepted for publication March 2, 2004.

	References

Top Abstract Introduction Materials and Methods Results Discussion References

 

1. Fowell, D., A. J. McKnight, F. Powrie, R. Dyke, D. Mason. 1991. Subsets of CD4⁺ T cells and their roles in the induction and prevention of autoimmunity. Immunol. Rev. 123:37.[Medline]
2. Itoh, M., T. Takahashi, N. Sakaguchi, Y. Kuniyasu, J. Shimizu, F. Otsuka, S. Sakaguchi. 1999. Thymus and autoimmunity: production of CD25⁺CD4⁺ naturally anergic and suppressive T cells as a key function of the thymus in maintaining immunologic self-tolerance. J. Immunol. 162:5317.[Abstract/Free Full Text]
3. Asano, M., M. Toda, N. Sakaguchi, S. Sakaguchi. 1996. Autoimmune disease as a consequence of developmental abnormality of a T cell subpopulation. J. Exp. Med. 184:387.[Abstract/Free Full Text]
4. Hori, S., T. Nomura, S. Sakaguchi. 2003. Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057.[Abstract/Free Full Text]
5. Fontenot, J. D., M. A. Gavin, A. Y. Rudensky. 2003. Foxp3 programs the development and function of CD4⁺CD25⁺ regulatory T cells. Nat. Immunol. 4:330.[Medline]
6. Khattri, R., T. Cox, S. A. Yasayko, F. Ramsdell. 2003. An essential role for Scurfin in CD4⁺CD25⁺ T regulatory cells. Nat. Immunol. 4:337.[Medline]
7. Atreya, R., J. Mudter, S. Finotto, J. Müllberg, T. Jostock, S. Wirtz, M. Schütz, B. Bartsch, M. Holtmann, C. Becker, et al 2000. Blockade of IL-6 trans-signaling suppresses T cell resistance against apoptosis in chronic intestinal inflammation: evidence in Crohn’s disease and experimental colitis in vivo. Nat. Med. 6:583.[Medline]
8. Shi, Y., J. Massague. 2003. Mechanisms of TGF- signaling from cell membrane to the nucleus. Cell 113:685.[Medline]
9. Neurath, M. F., I. Fuss, B. L. Kelsall, D. H. Presky, W. Waegell, W. Strober. 1996. Experimental granulomatous colitis in mice is abrogated by induction of TGF--mediated oral tolerance. J. Exp. Med. 183:2515.
10. Levings, M. K., R. Sangregorio, M. G. Roncarolo. 2001. Human CD25⁺CD4⁺ T regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J. Exp. Med. 193:1295.[Abstract/Free Full Text]
11. Apostolou, I., A. Sarukhan, L. Klein, H. von Boehmer. 2002. Origin of regulatory T cells with known specificity for antigen. Nat. Immunol. 3:756.[Medline]
12. Zhang, X., L. Izikson, L. Liu, H. L. Weiner. 2001. Activation of CD25⁺CD4⁺ regulatory T cells by oral antigen administration. J. Immunol. 167:4245.[Abstract/Free Full Text]
13. Piccirillo, C. A., J. J. Letterio, A. M. Thornton, R. S. McHugh, M. Mamura, H. Mizuhara, E. M. Shevach. 2002. CD4⁺CD25⁺ regulatory T cells can mediate suppressor function in the absence of transforming growth factor 1 production and responsiveness. J. Exp. Med. 196:237.[Abstract/Free Full Text]
14. Tiede, I., G. Fritz, S. Strand, D. Poppe, R. Dvorsky, D. Strand, H. A. Lehr, S. Wirtz, C. Becker, R. Atreya, et al 2003. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4⁺ T lymphocytes. J. Clin. Invest. 111:1133.[Medline]

This article has been cited by other articles:

				A. Yessoufou, A. Ple, K. Moutairou, A. Hichami, and N. A. Khan Docosahexaenoic acid reduces suppressive and migratory functions of CD4CD25 regulatory T-cells J. Lipid Res., December 1, 2009; 50(12): 2377 - 2388. [Abstract] [Full Text] [PDF]

				S. M. Faust, G. Lu, B. L. Marini, W. Zou, D. Gordon, Y. Iwakura, Y. Laouar, and D. K. Bishop Role of T Cell TGF{beta} Signaling and IL-17 in Allograft Acceptance and Fibrosis Associated with Chronic Rejection J. Immunol., December 1, 2009; 183(11): 7297 - 7306. [Abstract] [Full Text] [PDF]

				M. Colic, D. Gazivoda, D. Vucevic, I. Majstorovic, S. Vasilijic, R. Rudolf, Z. Brkic, and P. Milosavljevic Regulatory T-cells in Periapical Lesions Journal of Dental Research, November 1, 2009; 88(11): 997 - 1002. [Abstract] [Full Text] [PDF]

				L. E. Jeffery, F. Burke, M. Mura, Y. Zheng, O. S. Qureshi, M. Hewison, L. S. K. Walker, D. A. Lammas, K. Raza, and D. M. Sansom 1,25-Dihydroxyvitamin D3 and IL-2 Combine to Inhibit T Cell Production of Inflammatory Cytokines and Promote Development of Regulatory T Cells Expressing CTLA-4 and FoxP3 J. Immunol., November 1, 2009; 183(9): 5458 - 5467. [Abstract] [Full Text] [PDF]

				I D Iliev, I Spadoni, E Mileti, G Matteoli, A Sonzogni, G M Sampietro, D Foschi, F Caprioli, G Viale, and M Rescigno Human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells Gut, November 1, 2009; 58(11): 1481 - 1489. [Abstract] [Full Text] [PDF]

				S. Sugita, S. Horie, O. Nakamura, K. Maruyama, H. Takase, Y. Usui, M. Takeuchi, K. Ishidoh, M. Koike, Y. Uchiyama, et al. Acquisition of T Regulatory Function in Cathepsin L-Inhibited T Cells by Eye-Derived CTLA-2{alpha} during Inflammatory Conditions J. Immunol., October 15, 2009; 183(8): 5013 - 5022. [Abstract] [Full Text] [PDF]

				Y. Y. Wan and R. A. Flavell How Diverse--CD4 Effector T Cells and their Functions J Mol Cell Biol, October 1, 2009; 1(1): 20 - 36. [Abstract] [Full Text] [PDF]

				S. A. De Serres, M. H. Sayegh, and N. Najafian Immunosuppressive Drugs and Tregs: A Critical Evaluation! Clin. J. Am. Soc. Nephrol., October 1, 2009; 4(10): 1661 - 1669. [Abstract] [Full Text] [PDF]

				D. Howie, K. F. Nolan, S. Daley, E. Butterfield, E. Adams, H. Garcia-Rueda, C. Thompson, N. J. Saunders, S. P. Cobbold, Y. Tone, et al. MS4A4B Is a GITR-Associated Membrane Adapter, Expressed by Regulatory T Cells, Which Modulates T Cell Activation J. Immunol., October 1, 2009; 183(7): 4197 - 4204. [Abstract] [Full Text] [PDF]

				J. Nolting, C. Daniel, S. Reuter, C. Stuelten, P. Li, H. Sucov, B.-G. Kim, J. J. Letterio, K. Kretschmer, H.-J. Kim, et al. Retinoic acid can enhance conversion of naive into regulatory T cells independently of secreted cytokines J. Exp. Med., September 28, 2009; 206(10): 2131 - 2139. [Abstract] [Full Text] [PDF]

				U. Petrausch, S. M. Jensen, C. Twitty, C. H. Poehlein, D. P. Haley, E. B. Walker, and B. A. Fox Disruption of TGF-{beta} Signaling Prevents the Generation of Tumor-Sensitized Regulatory T Cells and Facilitates Therapeutic Antitumor Immunity J. Immunol., September 15, 2009; 183(6): 3682 - 3689. [Abstract] [Full Text] [PDF]

				Z. Cao, A. K. Wara, B. Icli, X. Sun, R. R. S. Packard, F. Esen, C. J. Stapleton, M. Subramaniam, K. Kretschmer, I. Apostolou, et al. Kruppel-like Factor KLF10 Targets Transforming Growth Factor-{beta}1 to Regulate CD4+CD25- T Cells and T Regulatory Cells J. Biol. Chem., September 11, 2009; 284(37): 24914 - 24924. [Abstract] [Full Text] [PDF]

				E. Tsantikos, C. Quilici, K. W. Harder, B. Wang, H.-J. Zhu, G. P. Anderson, D. M. Tarlinton, and M. L. Hibbs Perturbation of the CD4 T Cell Compartment and Expansion of Regulatory T Cells in Autoimmune-Prone Lyn-Deficient Mice J. Immunol., August 15, 2009; 183(4): 2484 - 2494. [Abstract] [Full Text] [PDF]

				I. L. Huibregtse, E. V. Marietta, S. Rashtak, F. Koning, P. Rottiers, C. S. David, S. J. H. van Deventer, and J. A. Murray Induction of Antigen-Specific Tolerance by Oral Administration of Lactococcus lactis Delivered Immunodominant DQ8-Restricted Gliadin Peptide in Sensitized Nonobese Diabetic Ab{degrees} Dq8 Transgenic Mice J. Immunol., August 15, 2009; 183(4): 2390 - 2396. [Abstract] [Full Text] [PDF]

				A. MAHENDRA, R. MISRA, and A. AGGARWAL Th1 and Th17 Predominance in the Enthesitis-related Arthritis Form of Juvenile Idiopathic Arthritis J Rheumatol, August 1, 2009; 36(8): 1730 - 1736. [Abstract] [Full Text] [PDF]

				W. Chen and J. E. Konkel TGF-{beta} and 'Adaptive' Foxp3+ Regulatory T cells J Mol Cell Biol, July 31, 2009; (2009) mjp004v1. [Abstract] [Full Text] [PDF]

				X. Chen, R. Das, R. Komorowski, A. Beres, M. J. Hessner, M. Mihara, and W. R. Drobyski Blockade of interleukin-6 signaling augments regulatory T-cell reconstitution and attenuates the severity of graft-versus-host disease Blood, July 23, 2009; 114(4): 891 - 900. [Abstract] [Full Text] [PDF]

				T. R. Torgerson, A. Genin, C. Chen, M. Zhang, B. Zhou, S. Anover-Sombke, M. B. Frank, I. Dozmorov, E. Ocheltree, P. Kulmala, et al. FOXP3 Inhibits Activation-Induced NFAT2 Expression in T Cells Thereby Limiting Effector Cytokine Expression J. Immunol., July 15, 2009; 183(2): 907 - 915. [Abstract] [Full Text] [PDF]

				Z.-Z. Yang, A. J. Novak, S. C. Ziesmer, T. E. Witzig, and S. M. Ansell Malignant B Cells Skew the Balance of Regulatory T Cells and TH17 Cells in B-Cell Non-Hodgkin's Lymphoma Cancer Res., July 1, 2009; 69(13): 5522 - 5530. [Abstract] [Full Text] [PDF]

				B. Weigmann and M. F Neurath Selective targeting of activated T cells in chronic intestinal inflammation Gut, June 1, 2009; 58(6): 747 - 748. [Full Text] [PDF]

				M. B. Ahmed, N. Belhadj Hmida, N. Moes, S. Buyse, M. Abdeladhim, H. Louzir, and N. Cerf-Bensussan IL-15 Renders Conventional Lymphocytes Resistant to Suppressive Functions of Regulatory T Cells through Activation of the Phosphatidylinositol 3-Kinase Pathway J. Immunol., June 1, 2009; 182(11): 6763 - 6770. [Abstract] [Full Text] [PDF]

				A. Andersson, S.-C. Yang, M. Huang, L. Zhu, U. K. Kar, R. K. Batra, D. Elashoff, R. M. Strieter, S. M. Dubinett, and S. Sharma IL-7 Promotes CXCR3 Ligand-Dependent T Cell Antitumor Reactivity in Lung Cancer J. Immunol., June 1, 2009; 182(11): 6951 - 6958. [Abstract] [Full Text] [PDF]

				I. Kryczek, R. Liu, G. Wang, K. Wu, X. Shu, W. Szeliga, L. Vatan, E. Finlayson, E. Huang, D. Simeone, et al. FOXP3 Defines Regulatory T Cells in Human Tumor and Autoimmune Disease Cancer Res., May 1, 2009; 69(9): 3995 - 4000. [Abstract] [Full Text] [PDF]

				S. Huber, F. R. Stahl, J. Schrader, S. Luth, K. Presser, A. Carambia, R. A. Flavell, S. Werner, M. Blessing, J. Herkel, et al. Activin A Promotes the TGF-{beta}-Induced Conversion of CD4+CD25- T Cells into Foxp3+ Induced Regulatory T Cells J. Immunol., April 15, 2009; 182(8): 4633 - 4640. [Abstract] [Full Text] [PDF]

				D. Haribhai, W. Lin, B. Edwards, J. Ziegelbauer, N. H. Salzman, M. R. Carlson, S.-H. Li, P. M. Simpson, T. A. Chatila, and C. B. Williams A Central Role for Induced Regulatory T Cells in Tolerance Induction in Experimental Colitis J. Immunol., March 15, 2009; 182(6): 3461 - 3468. [Abstract] [Full Text] [PDF]

				J. Ji and M. W. Cloyd HIV-1 binding to CD4 on CD4+CD25+ regulatory T cells enhances their suppressive function and induces them to home to, and accumulate in, peripheral and mucosal lymphoid tissues: an additional mechanism of immunosuppression Int. Immunol., March 1, 2009; 21(3): 283 - 294. [Abstract] [Full Text] [PDF]

				Y. Sakai, M. Honda, H. Fujinaga, I. Tatsumi, E. Mizukoshi, Y. Nakamoto, and S. Kaneko Common Transcriptional Signature of Tumor-Infiltrating Mononuclear Inflammatory Cells and Peripheral Blood Mononuclear Cells in Hepatocellular Carcinoma Patients Cancer Res., December 15, 2008; 68(24): 10267 - 10279. [Abstract] [Full Text] [PDF]

				M. Imarai, E. Candia, C. Rodriguez-Tirado, J. Tognarelli, M. Pardo, T. Perez, D. Valdes, S. Reyes-Cerpa, P. Nelson, C. Acuna-Castillo, et al. Regulatory T Cells Are Locally Induced during Intravaginal Infection of Mice with Neisseria gonorrhoeae Infect. Immun., December 1, 2008; 76(12): 5456 - 5465. [Abstract] [Full Text] [PDF]

				G.-J. Wang, Y. Liu, A. Qin, S. V. Shah, Z.-b. Deng, X. Xiang, Z. Cheng, C. Liu, J. Wang, L. Zhang, et al. Thymus Exosomes-Like Particles Induce Regulatory T Cells J. Immunol., October 15, 2008; 181(8): 5242 - 5248. [Abstract] [Full Text] [PDF]

				S. Radhakrishnan, R. Cabrera, E. L. Schenk, P. Nava-Parada, M. P. Bell, V. P. Van Keulen, R. J. Marler, S. J. Felts, and L. R. Pease Reprogrammed FoxP3+ T Regulatory Cells Become IL-17+ Antigen-Specific Autoimmune Effectors In Vitro and In Vivo J. Immunol., September 1, 2008; 181(5): 3137 - 3147. [Abstract] [Full Text] [PDF]

				S. K. Alford, G. D. Longmore, W. F. Stenson, and C. Kemper CD46-Induced Immunomodulatory CD4+ T Cells Express the Adhesion Molecule and Chemokine Receptor Pattern of Intestinal T Cells J. Immunol., August 15, 2008; 181(4): 2544 - 2555. [Abstract] [Full Text] [PDF]

				A. Fragale, L. Gabriele, E. Stellacci, P. Borghi, E. Perrotti, R. Ilari, A. Lanciotti, A. L. Remoli, M. Venditti, F. Belardelli, et al. IFN Regulatory Factor-1 Negatively Regulates CD4+CD25+ Regulatory T Cell Differentiation by Repressing Foxp3 Expression J. Immunol., August 1, 2008; 181(3): 1673 - 1682. [Abstract] [Full Text] [PDF]

				E. Godebu, D. Summers-Torres, M. M. Lin, B. J. G. Baaten, and L. M. Bradley Polyclonal Adaptive Regulatory CD4 Cells That Can Reverse Type I Diabetes Become Oligoclonal Long-Term Protective Memory Cells J. Immunol., August 1, 2008; 181(3): 1798 - 1805. [Abstract] [Full Text] [PDF]

				M. Nagar, H. Vernitsky, Y. Cohen, D. Dominissini, Y. Berkun, G. Rechavi, N. Amariglio, and I. Goldstein Epigenetic inheritance of DNA methylation limits activation-induced expression of FOXP3 in conventional human CD25-CD4+ T cells Int. Immunol., August 1, 2008; 20(8): 1041 - 1055. [Abstract] [Full Text] [PDF]

				L. Gil-Guerrero, J. Dotor, I. L. Huibregtse, N. Casares, A. B. Lopez-Vazquez, F. Rudilla, J. I. Riezu-Boj, J. Lopez-Sagaseta, J. Hermida, S. Van Deventer, et al. In Vitro and In Vivo Down-Regulation of Regulatory T Cell Activity with a Peptide Inhibitor of TGF-{beta}1 J. Immunol., July 1, 2008; 181(1): 126 - 135. [Abstract] [Full Text] [PDF]

				C. Reardon, A. Wang, and D. M. McKay Transient Local Depletion of Foxp3+ Regulatory T Cells during Recovery from Colitis via Fas/Fas Ligand-Induced Death J. Immunol., June 15, 2008; 180(12): 8316 - 8326. [Abstract] [Full Text] [PDF]

				C. Grant, U. Oh, K. Yao, Y. Yamano, and S. Jacobson Dysregulation of TGF-{beta} signaling and regulatory and effector T-cell function in virus-induced neuroinflammatory disease Blood, June 15, 2008; 111(12): 5601 - 5609. [Abstract] [Full Text] [PDF]

				A. Singh, W. F. Carson IV, E. R. Secor Jr, L. A. Guernsey, R. A. Flavell, R. B. Clark, R. S. Thrall, and C. M. Schramm Regulatory Role of B Cells in a Murine Model of Allergic Airway Disease J. Immunol., June 1, 2008; 180(11): 7318 - 7326. [Abstract] [Full Text] [PDF]

				M.-L. Chen, B.-S. Yan, Y. Bando, V. K. Kuchroo, and H. L. Weiner Latency-Associated Peptide Identifies a Novel CD4+CD25+ Regulatory T Cell Subset with TGF{beta}-Mediated Function and Enhanced Suppression of Experimental Autoimmune Encephalomyelitis J. Immunol., June 1, 2008; 180(11): 7327 - 7337. [Abstract] [Full Text] [PDF]

				S. Mittal, N. A. Marshall, L. Duncan, D. J. Culligan, R. N. Barker, and M. A. Vickers Local and systemic induction of CD4+CD25+ regulatory T-cell population by non-Hodgkin lymphoma Blood, June 1, 2008; 111(11): 5359 - 5370. [Abstract] [Full Text] [PDF]

				H. Hu, K. Fernando, H. Ni, and D. Weissman HIV Envelope Suppresses CD4+ T Cell Activation Independent of T Regulatory Cells J. Immunol., April 15, 2008; 180(8): 5593 - 5600. [Abstract] [Full Text] [PDF]

				L. Passerini, S. E. Allan, M. Battaglia, S. Di Nunzio, A. N. Alstad, M. K. Levings, M. G. Roncarolo, and R. Bacchetta STAT5-signaling cytokines regulate the expression of FOXP3 in CD4+CD25+ regulatory T cells and CD4+CD25- effector T cells Int. Immunol., March 1, 2008; 20(3): 421 - 431. [Abstract] [Full Text] [PDF]

				C. H. Cook, A. A. Bickerstaff, J.-J. Wang, T. Nadasdy, P. Della Pelle, R. B. Colvin, and C. G. Orosz Spontaneous Renal Allograft Acceptance Associated with "Regulatory" Dendritic Cells and IDO J. Immunol., March 1, 2008; 180(5): 3103 - 3112. [Abstract] [Full Text] [PDF]

				R. P. Singh, A. La Cava, and B. H. Hahn pConsensus Peptide Induces Tolerogenic CD8+ T Cells in Lupus-Prone (NZB x NZW)F1 Mice by Differentially Regulating Foxp3 and PD1 Molecules J. Immunol., February 15, 2008; 180(4): 2069 - 2080. [Abstract] [Full Text] [PDF]

				T. Bryn, S. Yaqub, M. Mahic, K. Henjum, E. M. Aandahl, and K. Tasken LPS-activated monocytes suppress T-cell immune responses and induce FOXP3+ T cells through a COX-2-PGE2-dependent mechanism Int. Immunol., February 1, 2008; 20(2): 235 - 245. [Abstract] [Full Text] [PDF]

				E. J.A. van Wanrooij, S. C.A. de Jager, T. van Es, P. de Vos, H. L. Birch, D. A. Owen, R. J. Watson, E. A.L. Biessen, G. A. Chapman, T. J.C. van Berkel, et al. CXCR3 Antagonist NBI-74330 Attenuates Atherosclerotic Plaque Formation in LDL Receptor-Deficient Mice Arterioscler Thromb Vasc Biol, February 1, 2008; 28(2): 251 - 257. [Abstract] [Full Text] [PDF]

				M. G. Torcia, V. Santarlasci, L. Cosmi, A. Clemente, L. Maggi, V. D. Mangano, F. Verra, G. Bancone, I. Nebie, B. S. Sirima, et al. Functional deficit of T regulatory cells in Fulani, an ethnic group with low susceptibility to Plasmodium falciparum malaria PNAS, January 15, 2008; 105(2): 646 - 651. [Abstract] [Full Text] [PDF]

				S. Li, E. J. Gowans, C. Chougnet, M. Plebanski, and U. Dittmer Natural Regulatory T Cells and Persistent Viral Infection J. Virol., January 1, 2008; 82(1): 21 - 30. [Full Text] [PDF]

				C. Siewert, U. Lauer, S. Cording, T. Bopp, E. Schmitt, A. Hamann, and J. Huehn Experience-Driven Development: Effector/Memory-Like {alpha}E+Foxp3+ Regulatory T Cells Originate from Both Naive T Cells and Naturally Occurring Naive-Like Regulatory T Cells J. Immunol., January 1, 2008; 180(1): 146 - 155. [Abstract] [Full Text] [PDF]

				S. Yamazaki, A. J. Bonito, R. Spisek, M. Dhodapkar, K. Inaba, and R. M. Steinman Dendritic cells are specialized accessory cells along with TGF- for the differentiation of Foxp3+ CD4+ regulatory T cells from peripheral Foxp3 precursors Blood, December 15, 2007; 110(13): 4293 - 4302. [Abstract] [Full Text] [PDF]

				Z.-W. Xia, L.-Q. Xu, W.-W. Zhong, J.-J. Wei, N.-L. Li, J. Shao, Y.-Z. Li, S.-C. Yu, and Z.-L. Zhang Heme Oxygenase-1 Attenuates Ovalbumin-Induced Airway Inflammation by Up-Regulation of Foxp3 T-Regulatory Cells, Interleukin-10, and Membrane-Bound Transforming Growth Factor- 1 Am. J. Pathol., December 1, 2007; 171(6): 1904 - 1914. [Abstract] [Full Text] [PDF]

				X. Chen, S. Vodanovic-Jankovic, B. Johnson, M. Keller, R. Komorowski, and W. R. Drobyski Absence of regulatory T-cell control of TH1 and TH17 cells is responsible for the autoimmune-mediated pathology in chronic graft-versus-host disease Blood, November 15, 2007; 110(10): 3804 - 3813. [Abstract] [Full Text] [PDF]

				J. Wei, O. Duramad, O. A. Perng, S. L. Reiner, Y.-J. Liu, and F. X.-F. Qin Antagonistic nature of T helper 1/2 developmental programs in opposing peripheral induction of Foxp3+ regulatory T cells PNAS, November 13, 2007; 104(46): 18169 - 18174. [Abstract] [Full Text] [PDF]

				D. Q. Tran, H. Ramsey, and E. M. Shevach Induction of FOXP3 expression in naive human CD4+FOXP3 T cells by T-cell receptor stimulation is transforming growth factor-{beta} dependent but does not confer a regulatory phenotype Blood, October 15, 2007; 110(8): 2983 - 2990. [Abstract] [Full Text] [PDF]

				R. J. DiPaolo, C. Brinster, T. S. Davidson, J. Andersson, D. Glass, and E. M. Shevach Autoantigen-Specific TGFbeta-Induced Foxp3+ Regulatory T Cells Prevent Autoimmunity by Inhibiting Dendritic Cells from Activating Autoreactive T Cells J. Immunol., October 1, 2007; 179(7): 4685 - 4693. [Abstract] [Full Text] [PDF]

				S. Hinz, L. Pagerols-Raluy, H.-H. Oberg, O. Ammerpohl, S. Grussel, B. Sipos, R. Grutzmann, C. Pilarsky, H. Ungefroren, H.-D. Saeger, et al. Foxp3 Expression in Pancreatic Carcinoma Cells as a Novel Mechanism of Immune Evasion in Cancer Cancer Res., September 1, 2007; 67(17): 8344 - 8350. [Abstract] [Full Text] [PDF]

				T. Tanijiri, T. Shimizu, K. Uehira, T. Yokoi, H. Amuro, H. Sugimoto, Y. Torii, K. Tajima, T. Ito, R. Amakawa, et al. Hodgkin's Reed-Sternberg cell line (KM-H2) promotes a bidirectional differentiation of CD4+CD25+Foxp3+ T cells and CD4+ cytotoxic T lymphocytes from CD4+ naive T cells J. Leukoc. Biol., September 1, 2007; 82(3): 576 - 584. [Abstract] [Full Text] [PDF]

				S. Dominitzki, M. C. Fantini, C. Neufert, A. Nikolaev, P. R. Galle, J. Scheller, G. Monteleone, S. Rose-John, M. F. Neurath, and C. Becker Cutting Edge: Trans-Signaling via the Soluble IL-6R Abrogates the Induction of FoxP3 in Naive CD4+CD25 T Cells J. Immunol., August 15, 2007; 179(4): 2041 - 2045. [Abstract] [Full Text] [PDF]

				J. L. Coombes, K. R.R. Siddiqui, C. V. Arancibia-Carcamo, J. Hall, C.-M. Sun, Y. Belkaid, and F. Powrie A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-{beta} and retinoic acid dependent mechanism J. Exp. Med., August 6, 2007; 204(8): 1757 - 1764. [Abstract] [Full Text] [PDF]

				C.-M. Sun, J. A. Hall, R. B. Blank, N. Bouladoux, M. Oukka, J. R. Mora, and Y. Belkaid Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid J. Exp. Med., August 6, 2007; 204(8): 1775 - 1785. [Abstract] [Full Text] [PDF]

				M. J. Benson, K. Pino-Lagos, M. Rosemblatt, and R. J. Noelle All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation J. Exp. Med., August 6, 2007; 204(8): 1765 - 1774. [Abstract] [Full Text] [PDF]

				M. Pyzik and C. A. Piccirillo TGF-{beta}1 modulates Foxp3 expression and regulatory activity in distinct CD4+ T cell subsets J. Leukoc. Biol., August 1, 2007; 82(2): 335 - 346. [Abstract] [Full Text] [PDF]

				S.-J. Liu, J.-P. Tsai, C.-R. Shen, Y.-P. Sher, C.-L. Hsieh, Y.-C. Yeh, A.-H. Chou, S.-R. Chang, K.-N. Hsiao, F.-W. Yu, et al. Induction of a distinct CD8 Tnc17 subset by transforming growth factor-{beta} and interleukin-6 J. Leukoc. Biol., August 1, 2007; 82(2): 354 - 360. [Abstract] [Full Text] [PDF]

				T. So and M. Croft Cutting Edge: OX40 Inhibits TGF-beta- and Antigen-Driven Conversion of Naive CD4 T Cells into CD25+Foxp3+ T cells J. Immunol., August 1, 2007; 179(3): 1427 - 1430. [Abstract] [Full Text] [PDF]

				K. Nakagome, M. Dohi, K. Okunishi, R. Tanaka, T. Kouro, M. R. Kano, K. Miyazono, J.-i. Miyazaki, K. Takatsu, and K. Yamamoto IL-5-Induced Hypereosinophilia Suppresses the Antigen-Induced Immune Response via a TGF-beta-Dependent Mechanism J. Immunol., July 1, 2007; 179(1): 284 - 294. [Abstract] [Full Text] [PDF]

				G. Cesana and H. L. Kaufman In Reply J. Clin. Oncol., June 20, 2007; 25(18): 2630 - 2632. [Full Text] [PDF]

				R. K. Selvaraj and T. L. Geiger A Kinetic and Dynamic Analysis of Foxp3 Induced in T Cells by TGF-beta J. Immunol., June 15, 2007; 178(12): 7667 - 7677. [Abstract] [Full Text] [PDF]

				J. Wong, R. Obst, M. Correia-Neves, G. Losyev, D. Mathis, and C. Benoist Adaptation of TCR Repertoires to Self-Peptides in Regulatory and Nonregulatory CD4+ T Cells J. Immunol., June 1, 2007; 178(11): 7032 - 7041. [Abstract] [Full Text] [PDF]

				Z. Yao, Y. Kanno, M. Kerenyi, G. Stephens, L. Durant, W. T. Watford, A. Laurence, G. W. Robinson, E. M. Shevach, R. Moriggl, et al. Nonredundant roles for Stat5a/b in directly regulating Foxp3 Blood, May 15, 2007; 109(10): 4368 - 4375. [Abstract] [Full Text] [PDF]

				L. E. Pereira, F. Villinger, N. Onlamoon, P. Bryan, A. Cardona, K. Pattanapanysat, K. Mori, S. Hagen, L. Picker, and A. A. Ansari Simian Immunodeficiency Virus (SIV) Infection Influences the Level and Function of Regulatory T Cells in SIV-Infected Rhesus Macaques but Not SIV-Infected Sooty Mangabeys J. Virol., May 1, 2007; 81(9): 4445 - 4456. [Abstract] [Full Text] [PDF]

				I. Peluso, D. Fina, R. Caruso, C. Stolfi, F. Caprioli, M. C. Fantini, G. Caspani, E. Grossi, L. Di Iorio, F. M. Paone, et al. Lactobacillus paracasei subsp. paracasei B21060 Suppresses Human T-Cell Proliferation Infect. Immun., April 1, 2007; 75(4): 1730 - 1737. [Abstract] [Full Text] [PDF]

				T. S. Davidson, R. J. DiPaolo, J. Andersson, and E. M. Shevach Cutting Edge: IL-2 Is Essential for TGF-beta-Mediated Induction of Foxp3+ T Regulatory Cells J. Immunol., April 1, 2007; 178(7): 4022 - 4026. [Abstract] [Full Text] [PDF]

				K. N. Couper, D. G. Blount, J. B. de Souza, I. Suffia, Y. Belkaid, and E. M. Riley Incomplete Depletion and Rapid Regeneration of Foxp3+ Regulatory T Cells Following Anti-CD25 Treatment in Malaria-Infected Mice J. Immunol., April 1, 2007; 178(7): 4136 - 4146. [Abstract] [Full Text] [PDF]

				D. Haribhai, W. Lin, L. M. Relland, N. Truong, C. B. Williams, and T. A. Chatila Regulatory T Cells Dynamically Control the Primary Immune Response to Foreign Antigen J. Immunol., March 1, 2007; 178(5): 2961 - 2972. [Abstract] [Full Text] [PDF]

				S. G. Zheng, J. Wang, P. Wang, J. D. Gray, and D. A. Horwitz IL-2 Is Essential for TGF-beta to Convert Naive CD4+CD25- Cells to CD25+Foxp3+ Regulatory T Cells and for Expansion of These Cells J. Immunol., February 15, 2007; 178(4): 2018 - 2027. [Abstract] [Full Text] [PDF]

				G. Yang, A. Liu, Q. Xie, T. B. Guo, B. Wan, B. Zhou, and J. Z. Zhang Association of CD4+CD25+Foxp3+ regulatory T cells with chronic activity and viral clearance in patients with hepatitis B Int. Immunol., February 1, 2007; 19(2): 133 - 140. [Abstract] [Full Text] [PDF]

				S. Nadkarni, C. Mauri, and M. R. Ehrenstein Anti-TNF-{alpha} therapy induces a distinct regulatory T cell population in patients with rheumatoid arthritis via TGF-{beta} J. Exp. Med., January 22, 2007; 204(1): 33 - 39. [Abstract] [Full Text] [PDF]

				I. Peluso, M. C. Fantini, D. Fina, R. Caruso, M. Boirivant, T. T. MacDonald, F. Pallone, and G. Monteleone IL-21 Counteracts the Regulatory T Cell-Mediated Suppression of Human CD4+ T Lymphocytes J. Immunol., January 15, 2007; 178(2): 732 - 739. [Abstract] [Full Text] [PDF]

				J. Bodor, Z. Fehervari, B. Diamond, and S. Sakaguchi Regulatory T cell-mediated suppression: potential role of ICER J. Leukoc. Biol., January 1, 2007; 81(1): 161 - 167. [Abstract] [Full Text] [PDF]

				P. Bochtler, C. Wahl, R. Schirmbeck, and J. Reimann Functional Adaptive CD4 Foxp3 T Cells Develop in MHC Class II-Deficient Mice J. Immunol., December 15, 2006; 177(12): 8307 - 8314. [Abstract] [Full Text] [PDF]

				C. A. Learn, P. E. Fecci, R. J. Schmittling, W. Xie, I. Karikari, D. A. Mitchell, G. E. Archer, Z. Wei, H. Dressman, and J. H. Sampson Profiling of CD4+, CD8+, and CD4+CD25+CD45RO+FoxP3+ T Cells in Patients with Malignant Glioma Reveals Differential Expression of the Immunologic Transcriptome Compared with T Cells from Healthy Volunteers Clin. Cancer Res., December 15, 2006; 12(24): 7306 - 7315. [Abstract] [Full Text] [PDF]

				J.-B. Sun, S. Raghavan, A. Sjoling, S. Lundin, and J. Holmgren Oral Tolerance Induction with Antigen Conjugated to Cholera Toxin B Subunit Generates Both Foxp3+CD25+ and Foxp3-CD25- CD4+ Regulatory T Cells J. Immunol., December 1, 2006; 177(11): 7634 - 7644. [Abstract] [Full Text] [PDF]

				J. Nilsson, A. Boasso, P. A. Velilla, R. Zhang, M. Vaccari, G. Franchini, G. M. Shearer, J. Andersson, and C. Chougnet HIV-1-driven regulatory T-cell accumulation in lymphoid tissues is associated with disease progression in HIV/AIDS Blood, December 1, 2006; 108(12): 3808 - 3817. [Abstract] [Full Text] [PDF]

				T. L. Sukiennicki and D. J. Fowell Distinct Molecular Program Imposed on CD4+ T Cell Targets by CD4+CD25+ Regulatory T Cells J. Immunol., November 15, 2006; 177(10): 6952 - 6961. [Abstract] [Full Text] [PDF]

				H. H. Uhlig, J. Coombes, C. Mottet, A. Izcue, C. Thompson, A. Fanger, A. Tannapfel, J. D. Fontenot, F. Ramsdell, and F. Powrie Characterization of Foxp3+CD4+CD25+ and IL-10-Secreting CD4+CD25+ T Cells during Cure of Colitis J. Immunol., November 1, 2006; 177(9): 5852 - 5860. [Abstract] [Full Text] [PDF]

				Z.-W. Xia, W.-W. Zhong, L.-Q. Xu, J.-L. Sun, Q.-X. Shen, J.-G. Wang, J. Shao, Y.-Z. Li, and S.-C. Yu Heme Oxygenase-1-Mediated CD4+CD25high Regulatory T Cells Suppress Allergic Airway Inflammation J. Immunol., November 1, 2006; 177(9): 5936 - 5945. [Abstract] [Full Text] [PDF]

				J. A. Kapp, K. Honjo, L. M. Kapp, X. y. Xu, A. Cozier, and R. P. Bucy TCR transgenic CD8+ T cells activated in the presence of TGF{beta} express FoxP3 and mediate linked suppression of primary immune responses and cardiac allograft rejection Int. Immunol., November 1, 2006; 18(11): 1549 - 1562. [Abstract] [Full Text] [PDF]

				S. Hue, P. Ahern, S. Buonocore, M. C. Kullberg, D. J. Cua, B. S. McKenzie, F. Powrie, and K. J. Maloy Interleukin-23 drives innate and T cell-mediated intestinal inflammation J. Exp. Med., October 30, 2006; 203(11): 2473 - 2483. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fantini, M. C. Articles by Neurath, M. F. Search for Related Content PubMed PubMed Citation Articles by Fantini, M. C. Articles by Neurath, M. F.