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The Journal of Immunology, 1999, 163: 1105-1109.
Copyright © 1999 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: RANTES Regulates Fas Ligand Expression and Killing by HIV-Specific CD8 Cytotoxic T Cells1

Fabienne Hadida*, Vincent Vieillard{dagger},{ddagger}, Lucile Mollet*, Ian Clark-Lewis§, Marco Baggiolini and Patrice Debré2,*

* Laboratoire d’Immunologie Cellulaire, Unité Mixte de Recherche 7627, Centre National de la Recherche Scientifique Bâtiment CERVI, Hôpital Pitié-Salpétrière, Paris, France; {dagger} Unité Mixte de Recherche 146, Centre National de la Recherche Scientifique, Institut Curie, Orsay, France; {ddagger} Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138; § Biomedical Research Centre, University of British Columbia, Vancouver, BC, Canada; and Theodor Kocher Institute, University of Bern, Bern, Switzerland


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results and Discussion
 References
 
Based on the previous observation that RANTES mediates the cytotoxic activity of human HIV-specific CD8+ T cells via the chemokine receptor CCR3, we studied the effect of this chemokine on different effector CD8+ cytolytic cells requiring Fas/Fas ligand (FasL) or perforin-dependent pathway. In CTLs derived from PBMCs of HIV-infected patients, both the spontaneous and the RANTES-induced cytotoxicity were inhibited by anti-FasL neutralizing Abs. In contrast, allogeneic CTLs or NK cells killing through perforin were not affected by RANTES and anti-FasL Ab. Accordingly, RANTES enhanced the expression of FasL in a concentration- and time-dependent manner in HIV-specific CTLs, whereas anti-RANTES Ab decreased markedly FasL expression. Finally, cell surface expression of FasL protein in HIV-specific CTLs was also up-regulated by eotaxin, a selective ligand for CCR3. Our observations show that the action of RANTES via CCR3 is necessary to regulate FasL expression on HIV-specific CD8+ T cells that kill through the Fas/FasL pathway.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results and Discussion
 References
 
The lytic activity of CD8+ T cells is mediated by two independent mechanisms, the release of perforin which kills target cells by forming pores in their plasma membrane, and the expression of Fas ligand (FasL)3 which induces apoptosis of Fas-bearing targets (1, 2). Although perforin is considered as the main mediator of the killing of virally infected cells by CTLs (3), Fas-dependent lytic pathways can act simultaneously and was demonstrated to contribute to the elimination of viral pathogens (4). Indeed, both mechanisms were observed during HIV infection and likely contribute to the characteristic depletion of CD4-bearing T cells (5).

Activated CD8+ HIV-specific CTLs were also shown to produce chemokines that may contribute to the overall HIV-suppressing activity. First, they were shown to compete for HIV coreceptor usage. More recently, we and others (6, 7) have demonstrated that chemokines also influence CD8 HIV-specific immune responses. In addition, it was shown that SDF-1 (stromal cell-derived factor-1) chemokine could increase TNF-{alpha}/TNFRII expression through CXCR-4 (8), questioning to what extend programmed cell death may depend upon a chemokine receptor ligation, particularly in HIV disease.

Because we have previously shown that RANTES enhances the HIV-specific cytotoxicity of CD8+ T cells (6), we have investigated the effect of this CC chemokine on both cytotoxicity pathways using HIV-specific MHC class I-restricted CTL lines established from infected individuals. Our data show that RANTES regulates FasL expression on HIV-specific CD8+ T cells that kill through the Fas/FasL pathway.


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

Eight individuals with a CD4 count ranging between 200 and 500/µl and no history of antiretroviral therapy were chosen as donors of PBMCs used to establish HIV-specific CTL lines (6).

Generation of HIV-1-specific and allogeneic CTL lines

PBMCs were isolated from venous blood of HIV-infected individuals by centrifugation over Ficoll-Hypaque density gradients (Eurobio, Les Ulis, France) and were activated overnight with irradiated PHA-stimulated (Murex, Dartford, U.K.) autologous PBMCs. Polyspecific CTL lines were generated by coculture with irradiated autologous PHA blasts in the presence of IL-2 (Boehringer Mannheim, Mannheim, Germany) and were used for the cytotoxicity assays after 20 days (6). CD8+ T cells accounted for >90% of the total. Allogeneic CTL lines were generated by culturing PBMCs from HIV seropositive individuals with irradiated allogeneic PHA blasts of healthy seronegative donors in the presence of IL-2. At day 21, CD8+ allogeneic CTLs were positively selected with anti-CD8-conjugated magnetic beads (5 beads/CD8+ cell; Dynal, Oslo, Norway). CD8+ T cells accounted for >95% of the preparation, and no NK cells were detected. Allogeneic specificity was assessed at days 11 and 21 using the appropriate PHA blasts and PHA blasts from control donors as target cells.

Cytotoxicity assays

HIV-specific CTL activity was tested against autologous EBV-transformed lymphoblastoid B cell lines (B-LCL) that were established from each CTL donor (6). The B-LCL were infected with wild-type vaccinia virus or with vaccinia virus expressing the HIVLAI proteins Gag, Pol, or Env (Transgene, Strasbourg, France) at a multiplicity of infection of 5 PFU/cell for 18 h at 37°C. They were then labeled for 2 h at 37°C with Na251CrO2 (100 µCi/106 cells; Amersham, Les Ulis, France) and washed twice with culture medium. The 51Cr-labeled target cells (4 x 103/well) were distributed in round-bottom 96-well microtiter plates (Dutcher, Brumath, France), and effector cells were added at E:T ratios ranging between 120:1 and 3:1. The plates were centrifuged and incubated for 4 h at 37°C. The supernatants were then harvested, and 51Cr release was measured in a gamma counter. Spontaneous 51Cr release values ranged between 10 and 20% of the total incorporated radioactivity. Relative, specific 51Cr release was calculated as described (9). All experiments were performed in triplicate. If not stated otherwise, the results are presented after subtraction of the lysis obtained with control targets. Standard error of triplicates was always <5% of the mean value and was omitted for clarity. NK activity was tested with freshly isolated PBMCs from healthy donors using K562 cells as target. The conditions for chromium release assays were the same as for the CTL assays.

RT-PCR analysis

Total RNA was isolated (9), and cDNA products were obtained from 1 µg of total RNA treated with DNase I (Promega, Charbonnière, France) using the First Strand Synthesis kit (Pharmacia Biotech, Orsay, France). To estimate transcript expression, cDNA products were amplified by PCR for 35 cycles using the FasL primer set, 5'-CGACTCTTCCACCTGCAGAAGG-3' and 5'-AGATTCCTCAAAATTGATCAGAGAGAG-3'; the perforin primer set, 5'-CCTAAGCCCACCAGCAATGTG-3' and 5'-GGTGGAGGCGTTGGGAAGTG-3'; and the CCR3 primer set, 5'-ATGACAACCTCACTAGATACAG-3' and 5'-AACACAATAGAGAGTTCC-3'. One-sixteenth of the cDNA products was amplified by PCR for 30 cycles in the presence of 1 µM [{alpha}-33P]dCTP (10 mCi/mM, NEN Life Science Products, Le Blanc Mesnil, France) to detect G3PDH transcripts. The reaction products were detected by autoradiography after electrophoresis on 4% nondenaturing polyacrylamide gels and were quantified in a PhosphorImager (Pharmacia Biotech).

Flow cytometry

Cell surface expression of FasL was assessed on CTLs using the anti-FasL FITC-conjugate clone H11 (Alexis, Paris, France) or anti-FasL (IgG2a, NOK-1) (PharMingen, San Diego, CA). For direct fluorescence analysis, 5 x 105 cells were incubated with 5 µg anti-FasL at 4°C for 30 min, washed with PBS, fixed with 1% paraformaldehyde in PBS, and analyzed in a FACScan flow cytometer (Becton Dickinson, San Jose, CA). For each sample, 105 events were collected and analyzed using the Cellquest software (Becton Dickinson). In staining by PharMingen mAb, CTLs were first incubated with 5 µg/ml anti-FasL at 4°C for 30 min, washed, and then incubated with 5 µg/ml FITC-goat anti-IgG2a (Tebu, Santa Cruz, CA).

Reagents

RANTES and eotaxin were prepared by chemical synthesis (10). They were added to the assays at the time of mixing effector and target cells. The following neutralizing mAbs were used: anti-RANTES (R&D Systems, Minneapolis, MN), anti-CCR3 (7B11; kindly provided by LeukoSite, Cambridge, MA), anti-Fas (clone ZB4; Immunotech, Marseille, France), anti-FasL FITC-conjugate clone H11 (Alexis), or anti-FasL (IgG2a, NOK-1; PharMingen). Pretreatment of effector or target cells was done with 1 µg/ml Ab in RPMI 1640 containing 10% FCS for 1 h at 37°C without washing to assure neutralizing activity during the cytotoxicity assay. Concanamycin A (CMA; Fluka, Saint-Quentin Fallavier, France) was used as inhibitor of perforin-dependent cytotoxicity (11, 12). Effector cells were preincubated with CMA 90 min before mixing with the target cells.


   Results and Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
References
 
RANTES acts on Fas/FasL effector CD8 T cells

The effect of RANTES and of its neutralizing Ab was studied on different effectors CD8 T cells using Fas/FasL or perforin-dependent cytolytic pathway. We first examined HIV-specific MHC class I-restricted CTL lines that were generated from PBMCs of HIV-infected donors. They were shown to kill through Fas/FasL cytolytic pathway, because their specific lysis was inhibited by anti-FasL neutralizing Ab, but not by CMA (13), a selective inhibitor blocking only the perforin-based cytotoxicity (Fig. 1Go, top panel). The cytotoxic activity of HIV-specific CTLs was also abrogated when the autologous B-LCL, which were used as targets, were pretreated with an anti-Fas neutralizing Ab, confirming that the killing occurred through the Fas/FasL pathway (data not shown). Interestingly the HIV-specific lysis mediated by these PBMC-derived Fas/FasL-dependent effector T cells was markedly enhanced by RANTES and suppressed by anti-RANTES or anti-CCR3 mAbs (Fig. 1Go, top panel). We then studied the effect of RANTES on perforin-dependent allogeneic CTLs and NK cells (Fig. 1Go, middle and bottom panels). The cytotoxicity of these effector cells was abrogated in presence of CMA but was not influenced by anti-FasL. In this context, addition of RANTES, anti-RANTES, or anti-CCR3 does not affect the specific killing.



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  		FIGURE 1. RANTES induces Fas/FasL-dependent killing by HIV-specific CTLs. The cytolytic activity of HIV-specific CTLs, allogeneic CTLs, and NK cells was compared in the presence or absence of inhibitors of the Fas/FasL or the perforin pathways (a neutralizing anti-FasL Ab and CMA, respectively). The HIV-specific CTL line was established from a HIV-infected donors and was assayed against autologous B cells infected with recombinant vaccinia virus expressing HIV-1 Pol Ags. The results are shown at an E:T ratio of 120:1. The allogeneic effector CTL line was generated by culturing PBMCs from a HIV-infected donor (HLA: A1/A24, B8/B44) with allogeneic, irradiated PHA blasts from a HIV seronegative, healthy donor (HLA: A3/A24, B8/B18) and was assayed against PHA blasts from the healthy donor. NK activity was tested with freshly isolated PBMCs from healthy donors using K562 cells as target. Where indicated, the additions (see Materials and Methods) were as follows: 1 µg/ml anti-FasL ({alpha}-Fas-L), 10 nM CMA, 25 nM RANTES, 1 µg/ml anti-RANTES ({alpha}-RANTES), and 1 µg/ml anti-CCR3 ({alpha}-CCR3). Cytotoxicity was assessed in a chromium release assay as described in Materials and Methods. The data are representative of 11 experiments for the HIV-specific CTLs (basal activity at an E:T ratio of 120:1, 20 ± 8%; activity after RANTES treatment, 53 ± 21%) and 3 experiments for the allogeneic CTLs and the NK cells.

 
Data obtained with a series of HIV-specific CTL lines established from several infected individuals following our culture conditions are presented in Fig. 2Go. In all CTL lines tested that responded to RANTES, anti-FasL neutralizing Ab suppressed both the spontaneous (Fig. 2GoA) and the RANTES-induced (Fig. 2GoB) cytotoxicity. This finding indicates that the action of RANTES is restricted to Fas/FasL-dependent effector T cells.



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  		FIGURE 2. Prevention of cytotoxicity mediated by HIV-specific CTLs with a neutralizing anti-FasL Ab. The cytolytic activity of HIV-specific CTLs from seven different HIV-infected donors was tested in the absence and presence of 1 µg/ml anti-FasL. The CTLs were either untreated (A) or treated with 25 nM RANTES (B). Transformed autologous B cells infected with recombinant vaccinia virus expressing Gag ({circ}), Pol ({square}), or Env ({triangleup}) were used as targets. The straight lines connect the lytic activity values obtained in the absence (-) and presence (+) of anti-FasL.

 
RANTES regulates the transcripts and cell surface expression of FasL

The data presented in Figs. 1Go and 2Go demonstrate that the killing by RANTES-dependent HIV-specific CTLs is mediated by the Fas/FasL pathway. We therefore studied the effect of RANTES on the expression of FasL mRNA in effector T cells. As shown in Fig. 3Go, RANTES enhanced the expression of FasL transcripts in a concentration-dependent manner without enhancing the expression of perforin or CCR3. In HIV-specific CTL lines from six different individuals, the enhancement was statistically significant (p < 0.02) in the presence of 25 or 100 nM RANTES. RANTES, by contrast, did not influence FasL mRNA expression in NK cells (data not shown). Fig. 4Go shows the time-dependent expression of FasL mRNA in HIV-specific CTLs. In the presence of RANTES, expression doubled within 4 h and was increased nearly 4-fold after 17 h. RANTES neutralization with an Ab, by contrast, led to a marked, progressive decrease FasL expression. Using flow cytometry, we finally examined the expression of FasL on the surface of HIV-specific CTL lines. Incubation with 25 or 100 nM RANTES for 4 h significantly enhanced the density of FasL as detected with fluorescence-labeled Abs and as shown in Fig. 5GoA for 100 nM RANTES. Because RANTES binds to several chemokine receptors that are found in T lymphocytes, namely CCR1 (14), CCR3 (15, 16), CCR4 (17), and CCR5 (18), these experiments were also performed with eotaxin, a selective ligand for CCR3, which was equally effective as RANTES (Fig. 5GoB), further indicating that the observed enhancement of FasL expression is CCR3 dependent.



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  		FIGURE 3. Concentration-dependent induction of FasL mRNA expression by RANTES. HIV-specific CTL lines established from HIV-infected donors were incubated for 4 h with increasing concentrations of RANTES. Total RNA was extracted, and cDNA specific for FasL (filled bars), perforin (gray bars), and CCR3 (open bars) was amplified by PCR and quantified in a PhosphorImager. G3PDH expression was tested for control. Similar data were obtained in six different experiments with HIV-specific CTL lines.

 


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  		FIGURE 4. Time course of FasL mRNA expression induced by RANTES in HIV-specific CTL lines. CTLs were incubated with 25 nM RANTES (filled bars) or a neutralizing anti-RANTES (gray bars) Ab and cDNA specific for FasL (top panel) and perforin (bottom panel) was amplified by PCR and quantified in a PhosphorImager at different times. G3PDH expression was tested for control. The data are representative of two experiments.

 


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  		FIGURE 5. RANTES-induced FasL cell surface expression on HIV-specific CTL lines established after Ag stimulation. Staining profiles of FasL on CTLs cell surface were analyzed by flow cytometry after treatment with different concentrations of RANTES or eotaxin. A, CTLs were treated for 4 h with or without 100 nM RANTES (solid and broken line, respectively). B, CTLs were treated under the same conditions with or without 25 nM of eotaxin (solid and broken line, respectively). Insets, Plots of mean fluorescence vs duration of the treatment. The data are representative of three experiments.

 
Our study shows that the HIV-specific CTLs could kill target cells expressing Gag, Pol, or Env epitopes by a mechanism that depends on the Fas/FasL pathway, and that RANTES regulates the expression of FasL in these cells. RANTES appears to be essential in the process and to act via CCR3, since the expression of FasL and the Fas/FasL killing observed in cytotoxicity assays were abrogated or markedly decreased by neutralizing Abs against either RANTES or CCR3. The present findings are appropriate to explain the mechanism of the formerly reported function of RANTES and CCR3 in the stimulation of cytotoxicity by HIV-specific CTLs (6). There is little information about the regulation of FasL expression in CTLs. It has been reported that engagement of the TCR induces the recruitment of preformed FasL (19) and/or its biosynthesis (20, 21, 22). In this paper, we present compelling evidence for FasL production triggered by a chemokine receptor, CCR3, which is known to be expressed on subsets of T cells after activation (21). The induction of FasL expression by stimulation with RANTES via CCR3 has some analogy with the reported ability of SDF-1 and of Env epitopes binding to CXCR4 to induce apoptosis by the TNF-{alpha}/TNFRII death pathway (8). In combining chemotactic recruitment via CCR1 and CCR5, and lytic activity via CCR3, RANTES may play a key role in HIV-specific immune responses. The observed stimulation of FasL expression by RANTES can be seen as a defence mechanism leading to the elimination of HIV-infected cells, which is likely to function in concert with the HIV-suppressive activity of the same chemokine as blocker of CCR5. On the other hand, enhanced expression of FasL in CTLs may also contribute to pathogenesis by accelerating the decline of CD4+ or CD8+ cells that express Fas (5). The identification of RANTES and CCR3 as structurally defined effector molecules opens possibilities to devise therapeutic measures to regulate apoptosis of virus infected targets (23).


   Acknowledgments
 
We thank Drs. Georges Bismuth, Philippe Deterre, and Jean-Marc Ledoussal for discussions and suggestions.


   Footnotes
 
1 This work was supported by the Agence Nationale pour la Recherche sur le Sida (ANRS), the Swiss National Science Foundation, and the Protein Engineering Network of Centers of Excellence (PENCE), Canada. Back

2 Address correspondence and reprint requests to Dr. Patrice Debré, Laboratoire d’Immunologie Cellulaire, UMR 7627, Centre National de la Recherche Scientifique, Bâtimont CERVI, Hôpital Pitié-Salpétriére, 75651 Paris, France. E-mail address: Back

3 Abbreviations used in this paper: FasL, Fas ligand; CMA, concanamycin A; B-LCL, lymphoblastoid B cell line. Back

Received for publication April 26, 1999. Accepted for publication May 18, 1999.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results and Discussion
 References
 

  1. Kagi, D., F. Vignaux, B. Ledermann, K. Burki, V. Depraetere, S. Nagata, H. Hengartner, P. Golstein. 1994. Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science 265:528.[Abstract/Free Full Text]
  2. Lowin, B., M. Hahne, C. Mattmann, J. Tschopp. 1994. Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature 370:650.[Medline]
  3. Kagi, D., B. Ledermann, K. Burki, R. M. Zinkernagel, H. Hengartner. 1996. Molecular mechanisms of lymphocyte-mediated cytotoxicity and their role in immunological protection and pathogenesis in vivo. Annu. Rev. Immunol. 14:207.[Medline]
  4. Topham, D. J., R. A. Tripp, P. C. Doherty. 1997. CD8+ T cells clear influenza virus by perforin or Fas-dependent processes. J. Immunol. 159:5197.[Abstract]
  5. Badley, A. D., D. Dockrell, M. Simpson, R. Schut, D. H. Lynch, P. Leibson, C. V. Paya. 1997. Macrophage-dependent apoptosis of CD4+ T lymphocytes from HIV-infected individuals is mediated by FasL and tumor necrosis factor. J. Exp. Med. 185:55.[Abstract/Free Full Text]
  6. Hadida, F., V. Vieillard, B. Autran, I. Clark Lewis, M. Baggiolini, P. Debré. 1998. HIV-specific T cell cytotoxicity mediated by RANTES via the chemokine receptor CCR3. J. Exp. Med. 188:609.[Abstract/Free Full Text]
  7. 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]
  8. Herbein, G., U. Mahlknecht, F. Batliwalla, P. Gregersen, T. Pappas, J. Butler, W. A. O’Brien, E. Verdin. 1998. Apoptosis of CD8+ T cells is mediated by macrophages through interaction of HIV gp120 with chemokine receptor CXCR4. Nature 395:189.[Medline]
  9. Chomczynski, P., N. Sacchi. 1987. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162:156.[Medline]
  10. Clark, L. I., B. Moser, A. Walz, M. Baggiolini, G. J. Scott, R. Aebersold. 1991. Chemical synthesis, purification, and characterization of two inflammatory proteins, neutrophil activating peptide 1 (interleukin-8) and neutrophil activating peptide. Biochemistry 30:3128.[Medline]
  11. Woo, J. T., C. Shinohara, K. Sakai, K. Hasumi, A. Endo. 1992. Isolation, characterization and biological activities of concanamycins as inhibitors of lysosomal acidification. J. Antibiot. 45:1108.[Medline]
  12. Kataoka, T., M. Sato, S. Kondo, K. Nagai. 1996. Estimation of pH and the number of lytic granules in a CD8+ CTL clone treated with an inhibitor of vacuolar type H(+)-ATPase concanamycin A. Biosci. Biotechnol. Biochem. 60:1729.[Medline]
  13. Kataoka, T., N. Shinohara, H. Takayama, K. Takaku, S. Kondo, S. Yonehara, K. Nagai. 1996. Concanamycin A, a powerful tool for characterization and estimation of contribution of perforin- and Fas-based lytic pathways in cell-mediated cytotoxicity. J. Immunol. 156:3678.[Abstract]
  14. Loetscher, P., M. Seitz, M. Baggiolini, B. Moser. 1996. Interleukin-2 regulates CC chemokine receptor expression and chemotactic responsiveness in T lymphocytes. J. Exp. Med. 184:569.[Abstract/Free Full Text]
  15. Heath, H., S. Qin, P. Rao, L. Wu, G. LaRosa, N. Kassam, P. D. Ponath, C. R. Mackay. 1997. Chemokine receptor usage by human eosinophils: the importance of CCR3 demonstrated using an antagonistic monoclonal antibody. J. Clin. Invest. 99:178.[Medline]
  16. Yamada, H., K. Hirai, M. Miyamasu, M. Iikura, Y. Misaki, S. Shoji, T. Takaishi, T. Kasahara, Y. Morita, K. Ito. 1997. Eotaxin is a potent chemotaxin for human basophils. Biochem. Biophys. Res. Commun. 231:365.[Medline]
  17. Power, C. A., A. Meyer, K. Nemeth, K. B. Bacon, A. J. Hoogewerf, A. E. Proudfoot, T. N. Wells. 1995. Molecular cloning and functional expression of a novel CC chemokine receptor cDNA from a human basophilic cell line. J. Biol. Chem. 270:19495.[Abstract/Free Full Text]
  18. Samson, M., O. Labbe, C. Mollereau, G. Vassart, M. Parmentier. 1996. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry 35:3362.[Medline]
  19. Li, J. H., D. Rosen, D. Ronen, C. K. Behrens, P. H. Krammer, W. R. Clark, G. Berke. 1998. The regulation of CD95 ligand expression and function in CTL. J. Immunol. 161:3943.[Abstract/Free Full Text]
  20. Brunner, T., R. J. Mogil, D. LaFace, N. J. Yoo, A. Mahboubi, F. Echeverri, S. J. Martin, W. R. Force, D. H. Lynch, C. F. Ware, et al 1995. Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature 373:441.[Medline]
  21. Westendorp, M. O., R. Frank, C. Ochsenbauer, K. Stricker, J. Dhein, H. Walczak, K. M. Debatin, P. H. Krammer. 1995. Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature 375:497.[Medline]
  22. Vignaux, F., E. Vivier, B. Malissen, V. Depraetere, S. Nagata, P. Golstein. 1995. TCR/CD3 coupling to Fas-based cytotoxicity. J. Exp. Med. 181:781.[Abstract/Free Full Text]
  23. Viard, I., P. Wehrli, R. Bullani, P. Schneider, N. Holler, D. Salomon, T. Hunziker, J. H. Saurat, J. Tschopp, L. E. French. 1998. Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin. Science 282:490.[Abstract/Free Full Text]



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