Primed T cells are more resistant to Fas-mediated activation-induced cell death than naive T cells

Memory T cells respond in several functionally different ways from naive T cells and thus function as efficient effector cells. In this study we showe d that primed T cells were more resistant to Pas-mediated activation-induce d cell death (AICD) than naive T cells using OVA-specific TCR transgenic DO 10 mice and Fas-deficient DO10 lpr/lpr mice. We found that apoptosis was ef ficiently induced in activated naive T cells at 48 and 72 h after Ag restim ulation (OVA peptide; 0.3 and 3 mu M), whereas apoptosis was not significan tly increased in activated primed T cells at 24-72 h after Ag restimulation , We further showed that the resistance to AICD in primed T cells was due t o the decreased sensitivity to apoptosis induced by Pas-mediated signals, b ut TCR-mediated signaling equally activated both naive and primed T cells t o induce Fas and Fas ligand expressions. Furthermore, we demonstrated that primed T cells expressed higher levels of Fas-associated death domain-like IL-1 beta-converting enzyme inhibitory protein (FLIP), an inhibitor of Fas- mediated apoptosis, at 24-48 h after Ag restimulation than naive T cells. I n addition, Bcl-2 expression was equally observed between activated naive a nd primed T cells after Ag restimulation. Thus, these results indicate that naive T cells are sensitive to Pas-mediated AICD and are easily deleted by Ag restimulation, while primed/memory T cells express higher levels of FLI P after Ag restimulation, are resistant to Pas-mediated AICD, and thus func tion as efficient effector cells for a longer period.