FAS-INDUCED AND ACTIVATION-INDUCED APOPTOSIS ARE REDUCED IN HUMAN T-CELLS PREACTIVATED IN THE PRESENCE OF TGF-BETA

The elimination of activated but not resting T cells involves apoptosi s induced either by restimulation via the TCR/CD3 complex, CD2, or by signaling through the Fas Ag. The factors regulating the shift of an a poptosis-resistant to an apoptosis-sensitive phenotype and vice versa have not so far been clarified, Here we report that TGF-beta(1), when present during a PHA activation course, significantly increases viabil ity of human T cells upon reculture in medium alone, following restimu lation via CD2, CD3, or after triggering the Fas Ag, Using DNA gel ele ctrophoresis and an in situ nick translation technique we further show that activation-induced and Fas-mediated apoptosis are reduced in T c ells that were prestimulated with PHA plus TGF-beta(1), compared with control cells prestimulated with PHA alone, Moreover, when PHA-preacti vated T cells are further expanded in IL-2, inclusion of TGF-beta(1) r esults in higher cell yields at any timepoint from day 30 to 75 of cel l culture compared with control cultures without TGF-beta(1). However, no differences in Fas or bcl-2 protein expression are found between c ells stimulated in the absence or presence of TGF-beta(1). Together, o ur data identify TGF-beta(1), when present during an activation course , as an important viability factor possibly of importance for the gene ration of effector and/or long-lived memory T cells.