Monocyte-dependent death of freshly isolated T lymphocytes: induction by phorbolester and mitogens and differential effects of catalase.
Resting T cells are resistant to anti-Fas (CD95) mAb-mediated apoptosis but undergo apoptosis when triggered by anti-CD3 mAb or phorbolester PMA in the presence of PMA-activated monocytes. In this study, PMA, as well as the mitogens PHA and Con A, was found to induce death of resting T cells in the presence of autologous or allogeneic monocytes, while PWM was ineffective. Although several established monocytic and myelocytic cell lines were potent accessory cells for the mitogen-induced expansion of T lymphocytes, they all failed to replace plastic-adherent monocytes in the induction of monocyte-dependent cell death (MDCD) by PMA or PHA. CD45RA-positive cord blood T cells were as susceptible as peripheral blood T cells from adult donors to PMA-stimulated induction of MDCD. Using optimal concentrations of phorbolester, MDCD was inhibited neither by Fas-Fc fusion protein or neutralizing anti-Fas mAb, nor by inhibitors of IL-1beta-converting enzyme (ICE)-like proteases. In striking contrast, the H2O2 scavenger catalase completely prevented the PMA-stimulated T cell death, thereby revealing a potent mitogenic activity of PMA for human T cells in the presence of monocytes. Taken together, our results demonstrate that the accessory cell activity of monocytes/macrophages can be separated into "T cell death" and "T cell expansion" costimulatory functions, of which only the latter is mediated by established cell lines. Moreover, our results point to a pivotal role of reactive oxygen intermediates in the execution of MDCD triggered by PMA.
Department of Immunology, Paul-Ehrlich-Institute, Langen, Germany.
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D000328:Adult; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002374:Catalase / Q000494:pharmacology*; D002417:Cattle; D002448:Cell Adhesion / Q000276:immunology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002460:Cell Line; D002469:Cell Separation; D003208:Concanavalin A / Q000494:pharmacology*; D006801:Humans; D007231:Infant, Newborn; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000502:physiology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000276:immunology*; D010835:Phytohemagglutinins / Q000494:pharmacology*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010835:Phytohemagglutinins; D003208:Concanavalin A; D002374:Catalase; D013755:Tetradecanoylphorbol Acetate