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 apoptosi s but undergo apoptosis when triggered by anti-CD3 mAb or phorbolester PMA in the presence of PMA-activated monocytes. In this study, PMA, a s well as the mitogens PHA, and Con A, was found to induce death of re sting T cells in the presence of autologous or allogeneic monocytes, w hile PWM was ineffective. Although several established monocytic and m yelocytic cell lines were potent accessory cells for the mitogen-induc ed expansion of T lymphocytes, they all failed to replace plastic-adhe rent monocytes in the induction of monocyte-dependent cell death (MDCD ) by PMA or PHA, CD45RA-positive cord blood T cells were as susceptibl e as peripheral blood T cells from adult donors to PMA-stimulated indu ction of MDCD. Using optimal concentrations of phorbolester, MDCD was inhibited neither by Fas-Fc fusion protein or neutralizing anti-Fas mA b, nor by inhibitors of IL-1 beta-converting enzyme (ICE)-like proteas es, In striking contrast, the H2O2 scavenger catalase completely preve nted the PMA-stimulated T cell death, thereby revealing a potent mitog enic activity of PMA for human T cells in the presence of monocytes, T aken together, our results demonstrate that the accessory cell activit y 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 M DCD triggered by PMA.