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 Pericle, F.
Right arrow Articles by Segal, D. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pericle, F.
Right arrow Articles by Segal, D. M.
The Journal of Immunology, 1998, 160: 28-31.
Copyright © 1998 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: HIV-1 Infection Induces a Selective Reduction in STAT5 Protein Expression

Federica Pericle1,*, Ligia A. Pinto1,*, Stuart Hicks*, Robert A. Kirken{dagger}, Giuseppe Sconocchia*, Janice Rusnak{ddagger}, Matthew J. Dolan{ddagger}, Gene M. Shearer* and David M. Segal2,*

* Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD; {dagger} Intramural Research Support Program-Scientific Applications International Corporation, Frederick, Laboratory of Molecular Immunoregulation, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD; {ddagger} HIV Unit, Wilford Hall Medical Center, Lackland Air Force Base, TX.


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
HIV-1 infection is accompanied by qualitative and quantitative defects in CD4+ T lymphocytes. Loss of immune function in HIV patients is usually associated with a profound dysregulation of cytokine production. To investigate whether cytokine signaling defects occur during HIV infection, PHA blasts from healthy human donors were infected with two strains of HIV-1 and screened for the expression of STAT proteins used in cytokine signaling. A selective decrease in STAT5B was seen 8 days after infection with the BZ167 dual-tropic HIV isolate, but not with the Ba-L, M-tropic strain. Based on these findings, purified T cells from HIV-infected patients in different stages of disease were also tested for STAT expression; decreases in STAT5A, STAT5B, and STAT1{alpha} were observed in all patients. The reduction in STATs seen in vivo and in vitro after HIV infection may contribute to the loss of T cell function in HIV disease.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
HIV infection is associated with a progressive immune suppression, characterized by an early impairment of CD4+ T cell function and a later decline in absolute CD4+ T cell number (1, 2). Several recent studies have focused on the disruption of signaling pathways in T cells as possible causes for HIV-induced immune dysfunction; HIV-related alterations in src family protein tyrosine kinases (3, 4, 5, 6, 7), CD45 phosphatase (8), protein kinase C (9), intracellular Ca2+ (9), and ERK-2 and JNK kinases (10) have all been observed. Although it is not known whether these defects relate to the syndrome of HIV disease, it is likely that disruption of some of these signaling pathways would lead to losses in T cell functions.

A second factor that could account for the impairment of immune function in HIV-infected individuals is the profound alteration in cytokine secretion patterns seen in vivo and in vitro after HIV infection (11, 12, 13). The cytokines that a cell secretes typically depend upon the signals it receives from other cytokines in the medium. Most cytokines transduce biologic signals from cell surface receptors to the nucleus through the JAK-STAT signaling pathway (14, 15, 16). JAK kinases constitutively associate with the intracellular domains of cytokine receptors, and ligation with cytokine leads to JAK activation. STAT transcription factors are recruited to the activated cytokine receptor-JAK kinase complex where they are tyrosine phosphorylated. The phosphorylated STATs then translocate to the nucleus where they promote transcription of genes that control cell growth, differentiation, and maintenance of cellular homeostasis. Seven STAT genes, STATs 1–4, two closely related isoforms of STAT5, A and B, and STAT6 have been identified to date (16, 17). Of all the STATs, STAT5 is used most extensively in the signaling pathways of immunologically relevant cytokines, including IL-2, -3, -5, -7, -9, -15, and granulocyte-macrophage (GM)-CSF (18). Recently, we demonstrated that STAT5A and STAT5B protein and message were strongly depressed in tumor-bearing mice, while the expression of other members of the STAT family were unaltered (19). The selective reduction of STAT5 was associated with a loss in T and B cell function, suggesting that the STAT5 signaling pathway might play a crucial role in the tumor-dependent immunodeficiency. These observations raised the possibility that STAT down-regulation might also occur in other immunosuppressive conditions.

Therefore, in the current report we studied the expression of STAT proteins in T cells from normal donors following in vitro infection with HIV-1 and in T cells from HIV-infected patients. We show that in vitro HIV-1 infection can directly induce a selective down-modulation of STAT5B and that T cells from HIV-infected individuals have decreased expression of both STAT5A and -B.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Cells

PBMC were prepared from buffy coats from normal National Institutes of Health Blood Bank donors by Ficoll/Hypaque separation (20). PBL from HIV-infected patients were isolated by Ficoll-Hypaque separation and plastic adherence (21). CD3+ T cells were enriched from PBL by negative selection using a mAb mixture plus complement (Lymphokwik, One Lambda Inc., Los Angeles, CA). Patients were classified according to the Walter Reed guidelines for the staging of HIV-infected individuals (22). The use of human blood samples in these studies was approved by the Institutional Review Boards of both institutions.

Viral stocks

Two HIV-1 isolates were used in this study. HIV-1BZ167 was grown in human PHA blasts, as previously described (23). HIV-1Ba-L was grown in monocyte-derived macrophages. Cell-free supernatants were titered for p24 core Ag by ELISA (AIDS Vaccine Program, NCI, Frederick, MD).

HIV infection

PBMC (2 x 106/ml) were stimulated with 2 µg/ml PHA (Sigma, St. Louis, MO) for 3 days at 37°C, and washed twice. PHA blasts (105/sample) were incubated for 2 h with HIV-1BZ167 or HIV-1Ba-L (172 and 570 tissue culture ID50, respectively) and washed three times. Infected cells (1 x 106/ml) were incubated 3 or 8 days in medium supplemented with 10 U/ml of recombinant IL-2 (Boehringer Mannheim, Indianapolis, IN). Medium in the 8-day cultures was replaced 4 days after infection. HIV-1 infection was followed by ELISA for HIV-1 p24.

Immunoprecipitations

The immunoprecipitation procedure has been described previously (19). Briefly, 5 x 106 cells/group were incubated for 1 h at 4°C in Triton X-100 (1%) lysing buffer and spun. Supernatants were incubated with anti-STAT polyclonal Ab and adsorbed with protein A-Sepharose beads (Pharmacia, Piscataway, NJ). Adsorbed proteins were analyzed by SDS-PAGE under reducing conditions on a 7.5% homogeneous PhastGel (Pharmacia) followed by Western blotting with the same Ab used for immunoprecipitation. Proteins were detected by enhanced chemiluminescence.


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
In vitro HIV-1 infection reduces STAT5 expression

We previously showed that immunosuppression in tumor bearing mice was accompanied by a loss in STAT5 expression (19). To determine whether HIV infection would elicit a similar effect, PHA blasts from healthy, HIV-negative donors were infected with the primary HIV-1 isolate, BZ167, and STAT expression was assessed by immunoprecipitation and Western blotting 3 and 8 days after infection (Fig. 1Go). By day 8, when viral replication was well advanced (Table IGo), STAT5B expression was strikingly reduced. By contrast, STATs 1, 2, 3 and 5A were not significantly altered. No loss in STAT5B was observed 3 days after infection when viral replication was significantly less, indicating that STAT5B modulation occurred late in the infection cycle. Because gp120 and tat proteins have been found to affect immune function (24, 25, 26, 27), we tested whether culturing PHA blasts with either of these HIV-1 proteins would alter STAT5A or B expression. A mixture of recombinant gp120 and tat had no effect on STAT5A or B expression, and similar negative results were obtained when the cells were cultured for 3 or 8 days with either tat or gp120 alone (data not shown).



View larger version (38K):
[in this window]
[in a new window]
  		FIGURE 1. HIV-1-infected PBMC show a selective reduction of STAT5B expression. Cell lysates from 3- and 8-day cultures of uninfected and HIV-1BZ167-infected PHA blasts were immunoprecipitated and probed for the indicated STAT using the same Ab for both precipitation and Western blotting. Results are representative of three experiments.

 

View this table:
[in this window]
[in a new window]
  		Table I. HIV-1 p24 Ag production by HIV-1-infected PHA blasts

 
Preferential down-regulation of STAT5B by HIV-1BZ167

The capacity of the dual-tropic HIV-1 strain BZ167 to down-modulate STAT5B was compared with that of the M-tropic strain Ba-L. HIV-1BZ167 isolate (Fig. 2GoA), which uses predominantly CXCR4 and CCR3 coreceptors (D. Cohen, unpublished observation), markedly decreased STAT5B expression but had no effect on STAT1 or STAT5A, consistent with the results presented above. By contrast, the Ba-L M-tropic HIV-1 strain (Fig. 2GoB), which uses primarily CCR5 as coreceptor (28), had little effect on the expression of any of the three STATs examined. HIV-1BZ167 was significantly more virulent than HIV-1Ba-L (Table IGo), suggesting that the difference between the two strains in blocking STAT5B expression was due to differences in their abilities to infect the cells.



View larger version (37K):
[in this window]
[in a new window]
  		FIGURE 2. Decreased STAT5B expression in HIV-1BZ167- but not Ba-L-infected PHA blasts. PHA blasts from four separate donors were infected, cultured for 8 days, and tested for expression of the indicated STAT. Lanes 1 and 3, uninfected cells; lanes 2 and 4, cells infected with HIV-1BZ167 (A) or with HIV-1Ba-L (B). These data have been confirmed in three separate experiments.

 
STAT5A and -B are reduced in T cells from HIV-1-infected individuals

The capacity of HIV-1BZ167 to decrease STAT5B expression in infected PHA blasts raised the possibility that STAT levels might also be reduced in the T cells of HIV-1-infected donors. Purified T cells from 5 HIV-positive patients exhibiting a range of CD4 counts (Table IIGo) were examined for the levels of expression of STAT5 proteins. As seen in Figure 3Go, both STAT5A and STAT5B were markedly reduced in all 5 of the HIV-positive patients (P1 through P5), as compared with 2 HIV-negative (N1 and N2) control donors studied simultaneously. By contrast, STAT3, STAT6, and the lower m.w. splice variant of STAT1 (STAT1ß) showed near normal levels of protein expression in all donors. Interestingly, the higher m.w. variant, STAT1{alpha}, appeared to be absent in the cells from the infected patients. No quantitative correlation between the reduction in STAT protein and either the stage of the disease or therapy was observed in this small group of patients. Further studies in an extended group of patients will be necessary to elucidate the relationship between clinical characteristics and alteration in STAT expression. Reduced expression of STAT5A, STAT5B, and STAT1{alpha} in patients’ T cells differed from in vitro HIV-1-infected cultures in which the reduction was limited to STAT5B.


View this table:
[in this window]
[in a new window]
  		Table II. Clinical status of patients examined in Fig. 3Go

 


View larger version (47K):
[in this window]
[in a new window]
  		FIGURE 3. Reduced expression of STAT1{alpha}, STAT5A and STAT5B in T cells from HIV+ patients. Purified T cells from two healthy, HIV-negative (N) donors and five HIV-infected patients (P1-P5) were analyzed for STAT1, -3, -5A, -5B, and -6 expression. Patients’ disease status are indicated in Table IIGo. Shown are Western blots of immunoprecipitates using Abs against the indicated STATs.

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
In the current study we demonstrated that in vitro infection of PBMC or in vivo infection of patients with HIV-1 is accompanied by a marked decrease in the expression STAT5, a transcription factor used in the transduction of intracellular signals by a wide variety of cytokine receptors (14). In vitro infection of PHA blasts from HIV-negative donors with the dual-tropic HIV-1 strain BZ167 induced a selective loss of STAT5B protein. The specificity of this response was striking because it was not observed with any of the other STAT proteins examined, including the highly homologous STAT5A isoform (Fig. 1GoA). The loss in STAT5B protein may have been due to a decrease in its rate of synthesis or an increase in its degradation rate, but it was not due to its translocation to the nucleus since the lysis conditions used in our experiments released both cytoplasmic and nuclear STATs. In addition, the down-regulation of STAT5B was observed only late after infection with the BZ167 strain, and in cultures that were producing a high amount of virus, as measured by p24 release (Fig. 1Go, Table IGo). Infection of PHA blasts with the M-tropic strain HIV-1Ba-L failed to decrease STAT5B (Fig. 2GoB), possibly because the level of infection was much lower with this isolate than with HIV-1BZ167 (Table IGo). Most sexual transmissions of HIV-1 are caused by M-tropic viruses (29, 30); therefore, the down-regulation of STAT5B associated with the direct infection of T cells would likely occur in infected individuals only after the virus evolved in vivo into a T-tropic form.

The decrease in STAT5 and STAT1{alpha} expression in purified T cells from HIV infected patients was remarkable because it occurred in all five patients examined (Fig. 3Go), although these patients differed with respect to their disease stages and CD4+ T cell counts (Table IIGo). In contrast to in vitro infection of PHA blasts, STAT5A, STAT5B and STAT1{alpha} were all reduced in patients’ T cells. The loss of these STATs was selective because no consistent change was detected in the expression of STAT1ß, STAT3, and STAT6. Our preliminary finding that STAT1{alpha} but not -ß is lost in HIV+ patients could have profound immunologic consequences because the {alpha} and ß forms of STAT1 are splice variants, with STAT1ß acting as a dominant negative. Thus the loss of the {alpha} form of STAT1 could lead to abrogation of STAT1 function, which in deficient mice produces impaired innate immunity to viral infections (15). Since most peripheral blood T cells are not infected in HIV+ patients (31), it is unlikely that the loss in STAT5 and STAT1{alpha} seen in lysates from patients’ T cells was due to a direct effect of the virus on STAT expression. A more likely mechanism is that HIV-1 induced the secretion of one or more factors that resulted in STAT down-regulation.

Decreased STAT5 expression has now been observed in two unrelated diseases that cause immunosuppression, HIV disease in humans and experimentally induced mammary carcinoma in mice (19). The role that STAT5 plays in the impairment of immune function in these diseases is not known. However, because STAT5 has a broad spectrum of cytokine usage, its loss would be expected to strongly influence the immune system. The present study is the first to suggest that regulation of STAT5 may be involved in modulating cytokine profiles and immune function in HIV-infected patients. This study, as well as the previous report demonstrating STAT5 decreases in tumor-bearing mice (19), suggests that the regulation of STAT signaling pathways may provide a molecular mechanism that the immune system uses to control its level of activity.


   Footnotes
 
1 Contributed equally to this study. Back

2 Address correspondence and reprint requests to Dr. David Segal, Building 10, Room 4B17, National Institutes of Health, Bethesda, MD 20892. E-mail address: Back

Received for publication August 13, 1997. Accepted for publication October 28, 1997.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Miedema, F., A. J. Petit, F. G. Terpstra, J. K. Schattenkerk, F. de Wolf, B. J. Al, M. Roos, J. M. Lange, S. A. Danner, J. Goudsmit. 1988. Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men: HIV affects the immune system before CD4+ T helper cell depletion occurs. J. Clin. Invest. 82:1908.
  2. Fauci, A. S., G. Pantaleo, S. Stanley, D. Weissman. 1996. Immunopathogenic mechanisms of HIV infection. Ann. Intern. Med. 124:654.[Abstract/Free Full Text]
  3. Cayota, A., F. Vuillier, J. Siciliano, G. Dighiero. 1994. Defective protein tyrosine phosphorylation and altered levels of p59fyn and p56lck in CD4 T cells from HIV-1 infected patients. Int. Immunol. 6:611.[Abstract/Free Full Text]
  4. Kanner, S. B., O. K. Haffar. 1995. HIV-1 down-regulates CD4 costimulation of TCR/CD3-directed tyrosine phosphorylation through CD4/p56lck dissociation. J. Immunol. 154:2996.[Abstract]
  5. Guntermann, C., J. Dye, K. E. Nye. 1997. Human immunodeficiency virus infection abolishes CD4-dependent activation of ZAP-70 by inhibition of p56lck. J. Acquired Immune Defic. Syndr. Hum. Retrovirol. 14:204.[Medline]
  6. Morio, T., T. Chatila, R. S. Geha. 1997. HIV glycoprotein gp120 inhibits TCR-CD3-mediated activation of fyn and lck. Int. Immunol. 9:53.[Abstract/Free Full Text]
  7. Phipps, D. J., S. E. Read, J. P. Piovesan, G. B. Mills, D. R. Branch. 1996. HIV infection in vitro enhances the activity of src-family protein tyrosine kinases. AIDS 10:1191.[Medline]
  8. Cayota, A., F. Vuillier, G. Gonzalez, G. Dighiero. 1996. CD4+ lymphocytes from HIV-infected patients display impaired CD45- associated tyrosine phosphatase activity which is enhanced by anti- oxidants. Clin. Exp. Immunol. 104:11.[Medline]
  9. Nokta, M. A., M. I. Hassan, J. A. Morgan, K. A. Loesch, R. B. Pollard. 1994. Protein kinase C and intracellular free Ca++: relationship to human immunodeficiency virus (HIV)-induced cellular hyporesponsiveness. Proc. Soc. Exp. Biol. Med. 207:284.[Medline]
  10. Jabado, N., A. Pallier, S. Jauliac, A. Fischer, C. Hivroz. 1997. gp160 of HIV or anti-CD4 monoclonal antibody ligation of CD4 induces inhibition of JNK and ERK-2 activities in human peripheral CD4+ T lymphocytes. Eur. J. Immunol. 27:397.[Medline]
  11. Clerici, M., G. M. Shearer. 1994. The Th1-Th2 hypothesis of HIV infection: new insights. Immunol. Today 15:575.[Medline]
  12. Romagnani, S.. 1996. Understanding the role of Th1/Th2 cells in infection. Trends Microbiol. 4:470.[Medline]
  13. Klein, S. A., J. M. Dobmeyer, T. S. Dobmeyer, M. Pape, O. G. Ottmann, E. B. Helm, D. Hoelzer, R. Rossol. 1997. Demonstration of the Th1 to Th2 cytokine shift during the course of HIV- 1 infection using cytoplasmic cytokine detection on single cell level by flow cytometry. AIDS 11:1111.[Medline]
  14. O’Shea, J. J.. 1997. Jaks, STATs, cytokine signal transduction, and immunoregulation:are we there yet?. Immunity 7:1.[Medline]
  15. Ihle, J. N.. 1996. STATs: signal transducers and activators of transcription. Cell 84:331.[Medline]
  16. Darnell, J. E.. 1997. STATs and gene regulation. Science 277:1630.[Abstract/Free Full Text]
  17. Liu, X., G. W. Robinson, F. Gouilleux, B. Groner, L. Hennighausen. 1995. Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue. Proc. Natl. Acad. Sci. USA 92:8831.[Abstract/Free Full Text]
  18. Heim, M. H.. 1996. The Jak-STAT pathway: specific signal transduction from the cell membrane to the nucleus. Eur. J. Clin. Invest. 26:1.[Medline]
  19. Pericle, F., R. A. Kirken, V. Bronte, G. Sconocchia, L. DaSilva, D. M. Segal. 1997. Immunocompromised tumor-bearing mice show a selective loss of STAT5a/b expression in T and B lymphocytes. J. Immunol. 159:2580.[Abstract]
  20. Pinto, L. A., J. Sullivan, J. A. Berzofsky, M. Clerici, H. A. Kessler, A. L. Landay, G. M. Shearer. 1995. ENV-specific cytotoxic T lymphocyte responses in HIV seronegative health care workers occupationally exposed to HIV-contaminated body fluids. J. Clin. Invest. 96:867.
  21. Blauvelt, A., M. Clerici, D. R. Lucey, S. M. Steinberg, R. Yarchoan, R. Walker, G. M. Shearer, S. I. Katz. 1995. Functional studies of epidermal Langerhans cells and blood monocytes in HIV-infected persons. J. Immunol. 154:3506.[Abstract]
  22. Redfield, R. R., D. C. Wright, E. C. Tramont. 1986. The Walter Reed staging classification for HTLV-III/LAV infection. N. Engl. J. Med. 314:131.[Medline]
  23. Zolla-Pazner, S., J. O’Leary, S. Burda, M. K. Gorny, M. Kim, J. Mascola, F. McCutchan. 1995. Serotyping of primary human immunodeficiency virus type 1 isolates from diverse geographic locations by flow cytometry. J. Virol. 69:3807.[Abstract]
  24. Sakaida, H., T. Murakami, S. Kawamata, T. Hattori, T. Uchiyama. 1997. V3 loop of human immunodeficiency virus type 1 suppresses interleukin 2-induced T cell growth. AIDS Res. Hum. Retroviruses 13:151.[Medline]
  25. Chirmule, N., S. Pahwa. 1996. Envelope glycoproteins of human immunodeficiency virus type 1: profound influences on immune functions. Microbiol. Rev. 60:386.[Abstract/Free Full Text]
  26. Purvis, S. F., D. L. Georges, T. M. Williams, M. M. Lederman. 1992. Suppression of interleukin-2 and interleukin-2 receptor expression in Jurkat cells stably expressing the human immunodeficiency virus Tat protein. Cell. Immunol. 144:32.[Medline]
  27. Blazevic, V., M. Heino, A. Lagerstedt, A. Ranki, K. J. Krohn. 1996. Interleukin-10 gene expression induced by HIV-1 Tat and Rev in the cells of HIV-1 infected individuals. J. Acquired Immune Defic. Syndr. Hum. Retrovirol. 13:208.[Medline]
  28. Deng, H., R. Liu, W. Ellmeier, S. Choe, D. Unutmaz, M. Burkhart, P. Di Marzio, S. Marmon, R. E. Sutton, C. M. Hill, C. B. Davis, S. C. Peiper, T. J. Schall, D. R. Littman, N. R. Landau. 1996. Identification of a major co-receptor for primary isolates of HIV-1. Nature 381:661.[Medline]
  29. Moore, J. P.. 1997. Coreceptors: implications for HIV pathogenesis and therapy. Science 276:51.[Free Full Text]
  30. van’t Wout, A. B., N. A. Kootstra, G. A. Mulder-Kampinga, N. Albrecht-van Lent, H. J. Scherpbier, J. Veenstra, K. Boer, R. A. Coutinho, F. Miedema, H. Schuitemaker. 1994. Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission. J. Clin. Invest. 94:2060.
  31. Rosenberg, Z. F., A. S. Fauci. 1993. Immunology of HIV infection. W. E. Paul, ed. Fundamental Immunology 3rd ed.1375. Raven Press, Ltd, New York.



This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
H. Lin, M. Nieda, J. F. Hutton, V. Rozenkov, and A. J. Nicol
Comparative gene expression analysis of NKT cell subpopulations
J. Leukoc. Biol., July 1, 2006; 80(1): 164 - 173.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Zhang, R. A. Kirken, L. Furian, S. Janczewska, X. Qu, W. W. Hancock, M. Wang, N. Tejpal, R. Kerman, B. D. Kahan, et al.
Allograft Rejection Requires STAT5a/b-Regulated Antiapoptotic Activity in T Cells but Not B Cells
J. Immunol., January 1, 2006; 176(1): 128 - 137.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Petrovas, Y. M. Mueller, I. D. Dimitriou, P. M. Bojczuk, K. C. Mounzer, J. Witek, J. D. Altman, and P. D. Katsikis
HIV-Specific CD8+ T Cells Exhibit Markedly Reduced Levels of Bcl-2 and Bcl-xL
J. Immunol., April 1, 2004; 172(7): 4444 - 4453.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
T. J. Warby, S. M. Crowe, and A. Jaworowski
Human Immunodeficiency Virus Type 1 Infection Inhibits Granulocyte-Macrophage Colony-Stimulating Factor-Induced Activation of STAT5A in Human Monocyte-Derived Macrophages
J. Virol., December 1, 2003; 77(23): 12630 - 12638.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
M. Magnani, E. Balestra, A. Fraternale, S. Aquaro, M. Paiardini, B. Cervasi, A. Casabianca, E. Garaci, and C.-F. Perno
Drug-loaded red blood cell-mediated clearance of HIV-1 macrophage reservoir by selective inhibition of STAT1 expression
J. Leukoc. Biol., November 1, 2003; 74(5): 764 - 771.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
F. Behbod, Z. S. Nagy, S. M. Stepkowski, J. Karras, C. R. Johnson, W. D. Jarvis, and R. A. Kirken
Specific Inhibition of Stat5a/b Promotes Apoptosis of IL-2-Responsive Primary and Tumor-Derived Lymphoid Cells
J. Immunol., October 15, 2003; 171(8): 3919 - 3927.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
B. Samten, P. Ghosh, A.-K. Yi, S. E. Weis, D. L. Lakey, R. Gonsky, U. Pendurthi, B. Wizel, Y. Zhang, M. Zhang, et al.
Reduced Expression of Nuclear Cyclic Adenosine 5'-Monophospate Response Element-Binding Proteins and IFN-{gamma} Promoter Function in Disease Due to an Intracellular Pathogen
J. Immunol., April 1, 2002; 168(7): 3520 - 3526.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
M. Federico, Z. Percario, E. Olivetta, G. Fiorucci, C. Muratori, A. Micheli, G. Romeo, and E. Affabris
HIV-1 Nef activates STAT1 in human monocytes/macrophages through the release of soluble factors
Blood, November 1, 2001; 98(9): 2752 - 2761.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
F. Behbod, R. A. Erwin-Cohen, M.-E. Wang, B. W. Trawick, X. Qu, R. Verani, B. D. Kahan, S. M. Stepkowski, and R. A. Kirken
Concomitant Inhibition of Janus Kinase 3 and Calcineurin-Dependent Signaling Pathways Synergistically Prolongs the Survival of Rat Heart Allografts
J. Immunol., March 15, 2001; 166(6): 3724 - 3732.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
J. B. Johnston, Y. Jiang, G. van Marle, M. B. Mayne, W. Ni, J. Holden, J. C. McArthur, and C. Power
Lentivirus Infection in the Brain Induces Matrix Metalloproteinase Expression: Role of Envelope Diversity
J. Virol., August 15, 2000; 74(16): 7211 - 7220.
[Abstract] [Full Text]

Home page
 J. Immunol.Home page
S. Salvadori, G. Martinelli, and K. Zier
Resection of Solid Tumors Reverses T Cell Defects and Restores Protective Immunity
J. Immunol., February 15, 2000; 164(4): 2214 - 2220.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
C. Bovolenta, L. Camorali, A. L. Lorini, S. Ghezzi, E. Vicenzi, A. Lazzarin, and G. Poli
Constitutive Activation of STATs Upon In Vivo Human Immunodeficiency Virus Infection
Blood, December 15, 1999; 94(12): 4202 - 4209.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
J. D. Marshall, J. Chehimi, G. Gri, J. R. Kostman, L. J. Montaner, and G. Trinchieri
The Interleukin-12-Mediated Pathway of Immune Events Is Dysfunctional in Human Immunodeficiency Virus-Infected Individuals
Blood, August 1, 1999; 94(3): 1003 - 1011.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Yamashita, J. Xu, R. A. Erwin, W. L. Farrar, R. A. Kirken, and H. Rui
Differential Control of the Phosphorylation State of Proline-juxtaposed Serine Residues Ser725 of Stat5a and Ser730 of Stat5b in Prolactin-sensitive Cells
J. Biol. Chem., November 13, 1998; 273(46): 30218 - 30224.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. David, L. Bani, J.-L. Moreau, M.-P. Treilhou, T. Nakarai, M. Joussemet, J. Ritz, B. Dupont, G. Pialoux, and J. Theze
Regulatory dysfunction of the interleukin-2 receptor during HIV infection and the impact of triple combination therapy
PNAS, September 15, 1998; 95(19): 11348 - 11353.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Selliah and T. H. Finkel
Cutting Edge: JAK3 Activation and Rescue of T Cells from HIV gp120-Induced Unresponsiveness
J. Immunol., June 15, 1998; 160(12): 5697 - 5701.
[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 Pericle, F.
Right arrow Articles by Segal, D. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pericle, F.
Right arrow Articles by Segal, D. M.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS