Cutting edge: RANTES regulates Fas ligand expression and killing by HIV-specific CD8 cytotoxic T cells.
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.
Hadida
F
F
Laboratoire d'Immunologie Cellulaire, Unité Mixte de Recherche 7627, Centre National de la Recherche Scientifique Bâtiment CERVI, Hôpital Pitié-Salpétrière, Paris, France.
Vieillard
V
V
Mollet
L
L
Clark-Lewis
I
I
Baggiolini
M
M
Debré
P
P
D000276:Adjuvants, Immunologic / Q000502:physiology; D002460:Cell Line; D018946:Chemokine CCL5 / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D053222:Fas Ligand Protein; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism; D014158:Transcription, Genetic / Q000276:immunology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D018946:Chemokine CCL5; D018984:Epitopes, T-Lymphocyte; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D019014:fas Receptor