Requirement of Fas(CD95), CD45, and CD11a/CD18 in monocyte-dependent apoptosis of human T cells.
Our previous studies demonstrated that upon activation, monocytes (Mo) were able to sensitize peripheral blood T (PBT) cells to apoptosis induced by treatment with PMA. However, it is unknown what gene products provide the death signal to the sensitized PBT cells and how activated Mo enable PBT cells to become susceptible to apoptosis. Here, we show that PBT cells, but not Mo, express functional Fas ligand upon treatment with PMA. Moreover, this Mo-dependent T cell apoptosis could be blocked by a Fas-Ig fusion protein, as well as by a nonlytic mAb against Fas molecule. These results strongly suggest involvement of Fas-Fas ligand interaction in the death of PBT cells. Unlike Fas-induced apoptosis, however, Mo-dependent T cell death was completely inhibited by overexpression of the Bcl-2 protein, and PMA alone was sufficient to trigger apoptosis in T cells when Mo were included in culture. Furthermore, anti-CD11a, anti-CD18, or anti-CD45/CD45RA mAbs; could prevent PBT cells from death triggered by PMA plus Mo, suggesting that these Ags participate in the apoptotic process. The participation of CD45RA in the death of PBT cells was further demonstrated by the observation that the J45.01 cell line, a CD45-deficient variant of Jurkat cells, did not undergo apoptosis by this Mo-dependent mechanism. When transfected with cDNA encoding CD45RA, J45.01 cells acquired apoptotic response to PMA stimulation in the presence of Mo to a similar, but lesser, degree than normal Jurkat cells.
Wu
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MX
Division of Tumor Immunology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Ao
Z
Z
Hegen
M
M
Morimoto
C
C
Schlossman
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SF
D015703:Antigens, CD / Q000502:physiology*; D017209:Apoptosis / Q000276:immunology*; D001483:Base Sequence; D018821:CD18 Antigens / Q000502:physiology; D016923:Cell Death / Q000276:immunology; D053222:Fas Ligand Protein; D006801:Humans; D015458:Leukemia, T-Cell; D017493:Leukocyte Common Antigens / Q000502:physiology; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D008562:Membrane Glycoproteins / Q000097:blood; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000502:physiology
D015703:Antigens, CD; D018821:CD18 Antigens; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D019014:fas Receptor; D017493:Leukocyte Common Antigens; D013755:Tetradecanoylphorbol Acetate