The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Walzer, T.
Right arrow Articles by Marvel, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Walzer, T.
Right arrow Articles by Marvel, J.
The Journal of Immunology, 2003, 170: 1615-1619.
Copyright © 2003 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Immediate RANTES Secretion by Resting Memory CD8 T Cells Following Antigenic Stimulation 1

Thierry Walzer*, Antoine Marçais*, Frédéric Saltel{ddagger}, Chantal Bella{dagger}, Pierre Jurdic{ddagger} and Jacqueline Marvel2,*

* Institut National de la Santé et de la Recherche Médicale, Unité 503, and {dagger} Service Commun de Cytométrie, Institut Fédératif de Recherche 74, and {ddagger} Laboratoire de Biologie Moléculaire et Cellulaire, Ecole Normale Supérieure de Lyon, Lyon, France


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
The efficiency of CD8 memory response relies partially on the modification of cellular functional capacities. To identify effector functions that can be modified following priming, we have compared the chemokines produced by naive and memory CD8 T cells. Our results show that in contrast to naive cells, resting memory CD8 T cells contain high levels of RANTES mRNA. As a result, they have the capacity to rapidly secrete RANTES upon ex vivo antigenic stimulation. In contrast to that of IFN-{gamma}, RANTES secretion is mainly due to the translation of the pre-existing mRNA.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
A memory response to Ag is faster and more efficient than a primary response. This qualitative difference has been shown to result in part from increased proliferation and effector capacities of memory compared with naive T cells. Indeed, it is now well-established that memory CD8 T cells display some of their effector functions very rapidly after antigenic stimulation. This has been demonstrated for IFN-{gamma} secretion and in some systems for cytolytic activity (1, 2, 3, 4). Moreover, memory CD8 T cells display a new recirculation pattern leading to their preferential relocalization outside secondary lymphoid organs (3). These properties could be very important for the immunosurveillance and the rapid initiation of immune responses against pathogens. In this respect, another effector function of CD8 T cells, the secretion of chemokines, has not been assessed in memory compared with naive CD8 T cells.

Chemokines are a family of proteins that are mainly involved in coordinating cellular trafficking and therefore play an essential role in the recruitment of leukocytes to inflammatory sites. RANTES is a C-C chemokine, also termed C-C chemokine ligand 5, which binds three receptors: CCR1, CCR3, and CCR5 (5). In T cells, production of RANTES mRNA and protein, following in vitro activation, is a late event, occurring 3–5 days postactivation (6, 7). In contrast, other cell types such as endothelial, epithelial cells or monocytes express elevated levels of RANTES mRNA and proteins within hours of exposure to proinflammatory stimuli including TNF-{alpha}, IFN-{gamma}, viruses, or LPS (8, 9, 10, 11, 12).

In this article, we have used F5 TCR transgenic mice to compare the capacity of resting naive and memory CD8 T cells to secrete chemokines following antigenic stimulation. We demonstrate that memory CD8 T cells, that are not cytolytic ex vivo contain high levels of RANTES mRNA that confer on them the capacity, compared with naive CD8 T cells, to rapidly secrete high amounts of RANTES upon ex vivo antigenic stimulation.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Mice and immunizations

F5 and RAG-/-F5 mice are transgenic for a TCR recognizing the (366–374) peptide (nucleoprotein (NP) 68)3 derived from the influenza virus NP in the context of the MHC class I molecule H2-Db. Memory cells were generated in thymectomized F5 mice as previously described (13). In some experiments, F5 splenocytes were adoptively transferred in C57BL/10-recipient mice. Recipient mice were then injected s.c. with 5 x 107 EL-4-GFP-NP cells. This procedure induces a strong response of engrafted F5 CD8 T cells which leads to tumor rejection within 2 wk (14).

Cells and cell cultures

For short-term cultures (<6 h), a total of 5 x 104 CD8 cells were stimulated in 96-well plates with NP68 at a concentration of 10 nM or with anti-CD3 Abs coated to microtiter plates in the presence of 2 µg/ml anti-CD28 (37.51; BD PharMingen, San Diego, CA) Abs. For intracellular cytokine detection assays, cells were stimulated in the presence of 0.67 µl/ml Golgi-stop (BD PharMingen). For long-term cultures, F5 transgenic spleen cells (1.5 x 107 in 30 ml per flask) were stimulated with 1 nM peptide and 6 x 107 irradiated (3000 rad) C57BL/10 spleen cells in the presence of 5% cell culture supernatant containing IL-2. The final IL-2 content ranged from 100–150 U/ml. Lymph node or splenic CD8 T cells were purified by magnetic beads using a negative selection strategy as previously described (15). For sorting, purified CD8 T cells were stained with anti-CD8 (YTS169.4-PE; BD PharMingen) and anti-CD44 (IM-78.1-FITC, made in our laboratory) Abs. Naive CD44low or memory CD44int were sorted from naive or NP68 peptide-primed RAG-/-F5 mice as previously described. CD44high memory phenotype CD8 T cells were sorted from C57BL/10 mice (15).

Actinomycin D and cycloheximide (both from Sigma-Aldrich, L’Isle d’Abeau, France) were used at a concentration of 10 µg/ml. Cytokines were purchased from R&D Systems (Mountain View, CA) and used at the concentration of 100 ng/ml.

Multiprobe RNase protection assays

Chemokine or cytokine mRNA levels were measured by RNase protection assays using the Riboquant kit (BD PharMingen) following the instructions of the supplier. The quantity of protected RNAs was determined using a PhosphorImager and ImageQuant software (both from Molecular Dynamics, Sunnyvale, CA).

RANTES ELISA

An ELISA (quantikine kit used according to the supplier’s instructions; R&D Systems) was used to measure the RANTES contents in culture supernatant.

Intracellular cytokine staining

For cytokine staining the Cytofix/Cytoperm kit was used according to the manufacturer’s instructions (BD PharMingen). XMG1.2-PE (anti-IFN-{gamma}) Ab was purchased from BD PharMingen.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
In this study, we have compared the expression of different chemokines by naive and memory CD8 T cells generated in F5 mice as previously described (13). We first measured the level of expression of chemokine mRNA by naive and memory CD8 F5 cells following a brief period of peptide stimulation. Results in Fig. 1A show that the mRNA coding for lymphotactin, macrophage-inflammatory protein (MIP)1-{alpha}, and MIP1-{beta} is produced by both naive and memory subsets with similar kinetics and levels. The main difference between naive and memory cells was observed on resting cells before antigenic challenge. Indeed, CD8 T cells from primed F5 mice express high levels of mRNA coding for the chemokine RANTES. The low level of RANTES mRNA that is detected in CD8 T cells from naive mice was due to the presence of a small percentage of memory phenotype CD44high CD8 T cells (Fig. 1A, top panel) which do not express the F5 TCR and expand in thymectomized mice (15). Indeed, in RAG-/-F5 mice which do not contain CD44high CD8 T cells (Fig. 1B, top panel), RANTES could not be detected in naive CD44low T cells. In contrast, high levels of RANTES were found in CD44int memory cells (Fig. 1B). To determine whether RANTES mRNA up-regulation was a general feature of CD8 memory cells, we have sorted naive phenotype CD44low and memory phenotype CD44high CD8 T cells from C57BL/10 mice and measured their steady state level of RANTES mRNA. Memory phenotype CD44high CD8 T cells were found to express much higher levels of RANTES than naive phenotype CD44low CD8 T cells (Fig. 1C), confirming that expression of high levels of RANTES mRNA is a common characteristic of memory CD8 T cells.



View larger version (62K):
[in this window]
[in a new window]
  		FIGURE 1. Memory CD8 T cells constitutively express high levels of RANTES mRNA. A, Splenocytes from 3-mo-old naive or primed thymectomized F5 mice were stimulated in vitro with NP68 peptide. At the indicated time, cells were harvested and CD8 T cells were purified before RNA extraction and quantification. The level of RANTES mRNA in different CD8 subsets was measured by RNase protection. B, CD8 T cells were FACS-sorted from 3-mo-old naive (CD44low) or primed thymectomized (CD44high) RAG-/-F5 mice. C, CD44low naive phenotype and CD44high memory phenotype CD8 T cells were FACS-sorted from 3-mo-old C57BL/10 mice. The CD44 staining profile of purified CD8 T cells is shown for A and B. The percentage of CD44high CD8 T cells among F5 CD8 T cells is given in A.

 
We next tested whether the increased levels of RANTES mRNA contained in CD8 memory cells leads to an increased production of RANTES protein by these cells. CD8 T cells from naive or primed RAG-/-F5 were purified and cultured for 6 h in the presence or absence of NP68 peptide. Results in Fig. 2A show that naive CD8 T cells, whether stimulated by the peptide or not, did not produce any detectable amount of RANTES. In contrast, following peptide stimulation, RANTES was rapidly secreted by memory CD8 T cells. In the absence of peptide, no RANTES protein could be detected in the supernatant, indicating that TCR engagement regulates the production of RANTES. Similarly, RANTES secretion by memory cells could not be triggered by different cytokines (Fig. 2B) that control its production in other cell types (10, 16). An early RANTES production was also found with F5 memory cells generated following transfer in a C57BL/10 host and priming with a NP68-expressing EL-4 tumor cell line (Fig. 2C). Similarly, activation of C57BL/10 CD8 T cells with plastic-bound anti-CD3 and soluble anti-CD28 leads to the secretion of RANTES by CD44high, but not by CD44low, CD8 T cells (Fig. 2D). These results indicate that in contrast to naive CD8 T cells, memory CD8 T cells generated in different systems are able to secrete high levels of RANTES.



View larger version (31K):
[in this window]
[in a new window]
  		FIGURE 2. Memory CD8 T cells rapidly secrete RANTES following antigenic stimulation. Naive and memory RAG-/-F5 CD8 T cells were respectively purified from 3-mo-old naive or primed thymectomized mice (A, B, E, and F). Naive and memory phenotype CD8 T cells were FACS-sorted from 3-mo-old C57BL/10 mice (D). Cells were then cultured as indicated for a period of 6 h (A, C, and D), 24 h (B), or a time course following peptide stimulation was performed (E and F). In E and F the following symbols are used: {blacksquare} for naive cells, {circ} for memory, {square} for memory cells in the presence of actinomycin D, and {triangleup} for memory cells in the presence of cycloheximide. C, F5 splenocytes were i.v. transferred in C57BL/10. One day later, EL4-GFP-NP cells were injected s.c. Control mice were not injected. Two months later, mice were sacrificed, CD8 T cells were purified from their spleen and lymph nodes and then cultured as indicated for 6 h with NP68. The level of RANTES in the culture supernatant was measured by ELISA.

 
A crucial parameter determining the outcome of a viral infection is the time required for the immune response to take place. Therefore, we have performed a time course study of RANTES production by naive and memory CD8 T cells following TCR engagement. Purified naive or memory CD8 T cells from RAG-/-F5 mice were stimulated in vitro with peptide and the concentration of RANTES produced in the culture supernatant was measured at different times. Results in Fig. 2E show that 20 min of stimulation are sufficient for memory CD8 T cells to secrete detectable levels of RANTES (50 pg/ml). In contrast naive cells require at least 72 h of stimulation to secrete comparable amounts of RANTES (Fig. 2F).

The production of RANTES by memory CD8 T cells was dependent on protein synthesis but largely independent of mRNA synthesis, as it was inhibited by cycloheximide but not by actinomycin D (Fig. 2E). However, the production of RANTES by memory CD8 T cells was never completely inhibited by the addition of cycloheximide suggesting that some cells might also contain pre-existing RANTES protein (Fig. 2E). This was confirmed by staining of freshly isolated naive or memory CD8 T cells. That showed that a fraction (i.e., 25%) of memory, but not naive, CD8 T cells contain low levels of RANTES protein. Following peptide stimulation, there was a 2-fold increase in the fraction of cells containing RANTES protein suggesting that in absence of stimulation some cells contain RANTES mRNA but no detectable protein (data not shown). Altogether, these results show that memory CD8 T cells contain high levels of RANTES mRNA that confer on them the unique capacity to rapidly secrete high amounts of RANTES upon ex vivo antigenic stimulation.

To study the kinetic of RANTES mRNA accumulation in CD8 T cells following priming in vivo, we have measured the expression of RANTES mRNA by CD8 T cells at different times after priming. The level of mRNA coding for MIP-1{beta}, another C-C chemokine that binds the same receptors as RANTES, was also measured. Indeed, its mRNA does not accumulate in memory cells and is produced at similar levels and with similar kinetics by both naive and memory CD8 T cells (Fig. 1A and data not shown). Results in Fig. 3 show that, in vivo, the mRNA coding for MIP-1{beta} is transiently expressed 6 h after activation before returning to the basal level found in resting cells. In contrast, the mRNA coding for RANTES is up-regulated late after T cell activation (day 5) and its expression is sustained at an elevated level at least until day 40 after priming. These results indicate that, in vivo, effector CD8 T cells are able to maintain high levels of RANTES mRNA when they differentiate into memory CD8 T cells allowing them to rapidly produce high levels of RANTES following TCR-mediated activation.



View larger version (16K):
[in this window]
[in a new window]
  		FIGURE 3. Late up-regulation and persistence of RANTES mRNA following in vivo CD8 activation. F5 mice were injected twice at 24-h intervals with 50 nmol of NP68 peptide. At the indicated times, mice were killed, spleen CD8 T cells were purified and RNA levels were quantified by RNase protection. For the first two time points, mice received only one injection of peptide. Mice used for the last time point were thymectomized.

 
The increased production of IFN-{gamma} by activated/memory CD8 or CD4 T cells has been shown to result from chromatin modifications that facilitate transcription of the IFN-{gamma} gene following T cell activation (17, 18). To determine whether transcription of the RANTES gene was also facilitated in memory CD8 T cells, we have measured RANTES and IFN-{gamma} mRNA levels in memory CD8 T cells following in vitro peptide stimulation (Fig. 4, A–C). Spleen cells from primed F5 mice were stimulated with peptide, CD8 T cells were purified, and their mRNA was isolated. The production of RANTES and IFN-{gamma} protein by memory cells following activation was also measured (Fig. 4D). Resting memory cells did not contain detectable amounts of IFN-{gamma} mRNA as measured by RNase protection assay (Fig. 4, A–C). However, following a brief peptide stimulation memory CD8 T cells were able to secrete IFN-{gamma}. This production was dependent on both RNA and protein synthesis (Fig. 4, A, C, and D). In contrast to IFN-{gamma}, a high level of RANTES mRNA was found in resting CD8 memory cells (Fig. 4, A and B). Following activation, RANTES mRNA first decreased steadily with time before being slowly up-regulated. This suggests that RANTES gene transcription following TCR engagement is not facilitated in memory CD8 T cells. Indeed, a similar late up-regulation of RANTES following TCR engagement is found following activation of naive cells in vivo (Fig. 3) or in vitro (data not shown and Refs.6 and7).



View larger version (30K):
[in this window]
[in a new window]
  		FIGURE 4. Different mechanisms are involved in the increased production of RANTES or IFN-{gamma} by memory CD8 T cells. A–C, Splenocytes from 3-mo-old primed thymectomized F5 mice were stimulated with peptide. CD8 T cells were purified after the indicated times and the level of RANTES and IFN-{gamma} mRNA was measured by RNase protection assay (A). RANTES (B) and IFN-{gamma} (C) mRNA levels were normalized using the internal control L32. D, CD8 T cells from primed F5 mice were stimulated, with or without Golgi-stop, for 5 h with peptide in the presence or absence of actinomycin D or cycloheximide.

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
One important characteristic of memory CD8 T cells is their capacity to display immediate effector functions following Ag contact. In this article, we show that memory CD8 T cells contain high levels of mRNA coding for the C-C chemokine RANTES and that they produce high levels of RANTES protein immediately after TCR triggering. Expression of RANTES mRNA or protein was found in all F5 memory CD8 T cells that we have tested whether generated directly in F5 mice by peptide priming or following transfer of F5 CD8 T cells in C57BL/10 host and priming with NP-68-EL-4 tumor. Expression of high levels of RANTES mRNA and protein by CD8 T cell clones has been previously described (19). However, these effector cells express RANTES in association with MIP1-{alpha}, MIP1-{beta}, perforin, and granzyme A and show a strong cytolytic activity in a 4-h assay (19). In contrast, resting RAG-/-F5 memory CD8 T cells express RANTES but not MIP1-{beta}. Based on their RNA content they are mainly in the G0 phase of the cell cycle and they are not cytolytic ex vivo in a 4-h assay (data not shown). Altogether this suggests that the maintenance of high levels of RANTES mRNA by memory CD8 T cells is independent of their cytolytic activity. Moreover, in CD8 T cell clones a large fraction of the RANTES secreted seems to be stored as pre-existing protein (19). In CD8 memory cells, prestored RANTES protein corresponds to <20% of the quantity that is secreted during the first 6 h. Therefore, increased production of RANTES by memory CD8 T cells relies mainly on prestored RANTES mRNA.

We show that in vivo following peptide stimulation, the level of RANTES mRNA in CD8 T cells becomes elevated by day 5 and is maintained at a similar level up to 40 days after priming. The mechanisms responsible for the maintenance of the increased level of RANTES mRNA are not known. It has been reported that the half-life of RANTES mRNA, even when stabilized following viral infection or treatment with IFN-{gamma} or TNF-{alpha}, did not exceed 25 h (8). Thus strongly suggesting that long-term maintenance of high levels of RANTES mRNA by memory CD8 T cells is dependent on the production of newly transcribed mRNA. However, we cannot exclude that in CD8 T cells, RANTES mRNA half life is increased. Indeed, several mechanisms acting on the 3'-UTR of RNA can lead to long-term stabilization of these macromolecules, this process being often associated with an inhibition of translation (20).

At the promoter level, the increased production of RANTES or IFN-{gamma} by memory CD8 T cells apparently relies on different mechanisms. Indeed, in memory cells, IFN-{gamma}-promoter activation by signaling through the TCR is increased and this is due in part to decreased methylation of the IFN-{gamma} promoter (18). In contrast, for RANTES a late mRNA up-regulation in response to TCR triggering is observed in both naive and memory cells. Thus, this indicates that the accessibility of the RANTES promoter for the transcription factors involved in its activation following TCR engagement has not been modified in memory CD8 T cells.

Early RANTES production by memory CD8 T cells could have major implications in the course of immunological responses against pathogens (21). Increased responsiveness associated with early RANTES production has been reported in DNA vaccine experiments which showed that coinjection of RANTES cDNA leads to an increased cytolytic activity and IFN-{gamma} production by Ag-specific CD8 T cells (22). Different properties of RANTES could explain this effect. Indeed, RANTES is a proinflammatory chemokine involved in the chemoattraction of a number of different effector cell types. Moreover, RANTES can act directly on CD8 T cells and increase their IFN-{gamma} production or their cytolytic activity via the up-regulation of Fas ligand (23). Finally, RANTES can act on immature dendritic cells inducing the production of TNF-{alpha} that might participate in the maturation of dendritic cells (24). A rapid RANTES production by memory CD8 T cells leading to the early recruitment of immune cells could therefore play an essential role in increased responsiveness characteristic of memory responses.

In conclusion, we show that expression of high levels of RANTES mRNA is a new hallmark of resting memory CD8 T cells that could contribute to the increased functional efficiency of these cells.


   Acknowledgments
 
We thank Drs. C. Arpin, Y. Leverrier, and J. L. Maryanski (Institut National de la Santé et de la Recherche Médicale, Unité 503, Lyon, France) for critical reading of the manuscript.


   Footnotes
 
1 T.W. was supported by a fellowship from the Association pour la Recherche sur le Cancer. This work was supported by institutional grants from Institut National de la Santé et de la Recherche Médicale and by additional support from Association pour la Recherche sur le Cancer and Région Rhône-Alpes (Contract 00816045). Back

2 Address correspondence and reprint requests to Dr. Jacqueline Marvel, Equipe Immuno-Apoptose, Institut National de la Santé et de la Recherche Médicale Unité 503, Centre d’Etude et de Recherche en Virologie et Immunologie, 21, avenue Tony Garnier, 69365 Lyon CEDEX 07, France. E-mail address: marvel@cervi-lyon.inserm.fr Back

3 Abbreviations used in this paper: NP, nucleoprotein; MIP, macrophage-inflammatory protein. Back

Received for publication October 25, 2002. Accepted for publication December 16, 2002.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Bachmann, M. F., M. Barner, A. Viola, M. Kopf. 1999. Distinct kinetics of cytokine production and cytolysis in effector and memory T cells after viral infection. Eur. J. Immunol. 29:291.[Medline]
  2. Kedl, R. M., M. F. Mescher. 1998. Qualitative differences between naive and memory T cells make a major contribution to the more rapid and efficient memory CD8+ T cell response. J. Immunol. 161:674.[Abstract/Free Full Text]
  3. Masopust, D., V. Vezys, A. L. Marzo, L. Lefrançois. 2001. Preferential localization of effector memory cells in nonlymphoid tissue. Science 291:2413.[Abstract/Free Full Text]
  4. Walzer, T., G. Joubert, P. M. Dubois, M. Tomkowiak, C. Arpin, M. Pihlgren, J. Marvel. 2000. Characterization at the single-cell level of naive and primed CD8 T cell cytokine responses. Cell. Immunol. 206:16.[Medline]
  5. Rossi, D., A. Zlotnik. 2000. The biology of chemokines and their receptors. Annu. Rev. Immunol. 18:217.[Medline]
  6. Ortiz, B. D., A. M. Krensky, P. J. Nelson. 1996. Kinetics of transcription factors regulating the RANTES chemokine gene reveal a developmental switch in nuclear events during T-lymphocyte maturation. Mol. Cell. Biol. 16:202.[Abstract]
  7. Ortiz, B. D., P. J. Nelson, A. M. Krensky. 1999. Switching gears during T-cell maturation: RANTES and late transcription. Immunity 10:93.[Medline]
  8. Koga, T., E. Sardina, R. M. Tidwell, M. Pelletier, D. C. Look, M. J. Holtzman. 1999. Virus-inducible expression of a host chemokine gene relies on replication-linked mRNA stabilization. Proc. Natl. Acad. Sci. USA 96:5680.[Abstract/Free Full Text]
  9. Lin, R., C. Heylbroeck, P. Genin, P. M. Pitha, J. Hiscott. 1999. Essential role of interferon regulatory factor 3 in direct activation of RANTES chemokine transcription. Mol. Cell. Biol. 19:959.[Abstract/Free Full Text]
  10. Marfaing-Koka, A., O. Devergne, G. Gorgone, A. Portier, T. J. Schall, P. Galanaud, D. Emilie. 1995. Regulation of the production of the RANTES chemokine by endothelial cells: synergistic induction by IFN-{gamma} plus TNF-{alpha} and inhibition by IL-4 and IL-13. J. Immunol. 154:1870.[Abstract]
  11. Shin, H. S., B. E. Drysdale, M. L. Shin, P. W. Noble, S. N. Fisher, W. A. Paznekas. 1994. Definition of a lipopolysaccharide-responsive element in the 5'-flanking regions of µRANTES and crg-2. Mol. Cell Biol. 14:2914.[Abstract/Free Full Text]
  12. Sundstrom, J. B., L. K. McMullan, C. F. Spiropoulou, W. C. Hooper, A. A. Ansari, C. J. Peters, P. E. Rollin. 2001. Hantavirus infection induces the expression of RANTES and IP-10 without causing increased permeability in human lung microvascular endothelial cells. J. Virol. 75:6070.[Abstract/Free Full Text]
  13. Pihlgren, M., P. M. Dubois, M. Tomkowiak, T. Sjogren, J. Marvel. 1996. Resting memory CD8+ T cells are hyperreactive to antigenic challenge in vitro. J. Exp. Med. 184:2141.[Abstract/Free Full Text]
  14. Wolkers, M. C., G. Stoetter, F. A. Vyth-Dreese, T. N. Schumacher. 2001. Redundancy of direct priming and cross-priming in tumor-specific CD8+ T cell responses. J. Immunol. 167:3577.[Abstract/Free Full Text]
  15. Walzer, T., C. Arpin, L. Beloeil, J. Marvel. 2002. Differential in vivo persistence of two subsets of memory phenotype CD8 T cells defined by CD44 and CD122 expression levels. J. Immunol. 168:2704.[Abstract/Free Full Text]
  16. Perera, L. P., C. K. Goldman, T. A. Waldmann. 1999. IL-15 induces the expression of chemokines and their receptors in T lymphocytes. J. Immunol. 162:2606.[Abstract/Free Full Text]
  17. Agarwal, S., A. Rao. 1998. Modulation of chromatin structure regulates cytokine gene expression during T cell differentiation. Immunity 9:765.[Medline]
  18. Fitzpatrick, D. R., K. M. Shirley, L. E. McDonald, H. Bielefeldt-Ohmann, G. F. Kay, A. Kelso. 1998. Distinct methylation of the interferon {gamma} (IFN-{gamma}) and interleukin 3 (IL-3) genes in newly activated primary CD8+ T lymphocytes: regional IFN-{gamma} promoter demethylation and mRNA expression are heritable in CD44highCD8+ T cells. J. Exp. Med. 188:103.[Abstract/Free Full Text]
  19. Wagner, L., O. O. Yang, E. A. Garcia-Zepeda, Y. Ge, S. A. Kalams, B. D. Walker, M. S. Pasternack, A. D. Luster. 1998. {beta}-Chemokines are released from HIV-1-specific cytolytic T-cell granules complexed to proteoglycans. Nature 391:908.[Medline]
  20. Richter, J. D., L. J. Lorenz. 2002. Selective translation of mRNAs at synapses. Curr. Opin. Neurobiol. 12:300.[Medline]
  21. Dorner, B. G., A. Scheffold, M. S. Rolph, M. B. Huser, S. H. Kaufmann, A. Radbruch, I. E. Flesch, R. A. Kroczek. 2002. MIP-1{alpha}, MIP-1{beta}, RANTES, and ATAC/lymphotactin function together with IFN-{gamma} as type 1 cytokines. Proc. Natl. Acad. Sci. USA 99:6181.[Abstract/Free Full Text]
  22. Kim, J. J., L. K. Nottingham, J. I. Sin, A. Tsai, L. Morrison, J. Oh, K. Dang, Y. Hu, K. Kazahaya, M. Bennett, et al 1998. CD8 positive T cells influence antigen-specific immune responses through the expression of chemokines. J. Clin. Invest. 102:1112.[Medline]
  23. Hadida, F., V. Vieillard, L. Mollet, I. Clark-Lewis, M. Baggiolini, P. Debre. 1999. Cutting edge: RANTES regulates Fas ligand expression and killing by HIV-specific CD8 cytotoxic T cells. J. Immunol. 163:1105.[Abstract/Free Full Text]
  24. Fischer, F. R., Y. Luo, M. Luo, L. Santambrogio, M. E. Dorf. 2001. RANTES-induced chemokine cascade in dendritic cells. J. Immunol. 167:1637.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 J. Immunol.Home page
F.-M. Mbitikon-Kobo, M. Vocanson, M.-C. Michallet, M. Tomkowiak, A. Cottalorda, G. S. Angelov, C.-A. Coupet, S. Djebali, A. Marcais, B. Dubois, et al.
Characterization of a CD44/CD122int Memory CD8 T Cell Subset Generated under Sterile Inflammatory Conditions
J. Immunol., March 15, 2009; 182(6): 3846 - 3854.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
C. G. Mueller, C. Boix, W.-H. Kwan, C. Daussy, E. Fournier, W. H. Fridman, and T. J. Molina
Critical role of monocytes to support normal B cell and diffuse large B cell lymphoma survival and proliferation
J. Leukoc. Biol., September 1, 2007; 82(3): 567 - 575.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y.-T. Ahn, B. Huang, L. McPherson, C. Clayberger, and A. M. Krensky
Dynamic Interplay of Transcriptional Machinery and Chromatin Regulates "Late" Expression of the Chemokine RANTES in T Lymphocytes
Mol. Cell. Biol., January 1, 2007; 27(1): 253 - 266.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Marcais, C.-A. Coupet, T. Walzer, M. Tomkowiak, R. Ghittoni, and J. Marvel
Cell-Autonomous CCL5 Transcription by Memory CD8 T Cells Is Regulated by IL-4
J. Immunol., October 1, 2006; 177(7): 4451 - 4457.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
I Tikhonov, C. Deetz, R Paca, S Berg, V Lukyanenko, J. Lim, and C. Pauza
Human V{gamma}2V{delta}2 T cells contain cytoplasmic RANTES
Int. Immunol., August 1, 2006; 18(8): 1243 - 1251.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Ramakrishna, R. A. Atkinson, S. A. Stohlman, and C. C. Bergmann
Vaccine-Induced Memory CD8+ T Cells Cannot Prevent Central Nervous System Virus Reactivation.
J. Immunol., March 1, 2006; 176(5): 3062 - 3069.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. N. Meissner, S. Swain, M. Tighe, A. Harmsen, and A. Harmsen
Role of Type I IFNs in Pulmonary Complications of Pneumocystis murina Infection
J. Immunol., May 1, 2005; 174(9): 5462 - 5471.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Ramakrishna, S. A. Stohlman, R. A. Atkinson, D. R. Hinton, and C. C. Bergmann
Differential Regulation of Primary and Secondary CD8+ T Cells in the Central Nervous System
J. Immunol., November 15, 2004; 173(10): 6265 - 6273.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
L. Sun, S. F. Abdelwahab, G. K. Lewis, and A. Garzino-Demo
Recall antigen activation induces prompt release of CCR5 ligands from PBMC: implication in memory responses and immunization
Int. Immunol., November 1, 2004; 16(11): 1623 - 1631.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. Quemeneur, L. Beloeil, M.-C. Michallet, G. Angelov, M. Tomkowiak, J.-P. Revillard, and J. Marvel
Restriction of De Novo Nucleotide Biosynthesis Interferes with Clonal Expansion and Differentiation into Effector and Memory CD8 T Cells
J. Immunol., October 15, 2004; 173(8): 4945 - 4952.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. K. Sojka, D. Bruniquel, R. H. Schwartz, and N. J. Singh
IL-2 Secretion by CD4+ T Cells In Vivo Is Rapid, Transient, and Influenced by TCR-Specific Competition
J. Immunol., May 15, 2004; 172(10): 6136 - 6143.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
L. Beloeil, M. Tomkowiak, G. Angelov, T. Walzer, P. Dubois, and J. Marvel
In Vivo Impact of CpG1826 Oligodeoxynucleotide on CD8 T Cell Primary Responses and Survival
J. Immunol., September 15, 2003; 171(6): 2995 - 3002.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Walzer, T.
Right arrow Articles by Marvel, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Walzer, T.
Right arrow Articles by Marvel, J.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS