Expression and function of Fas and Fas ligand on peripheral blood lymphocytes in normal subjects

We investigated the expression and function of Pas and Pas ligand (FasL) on peripheral blood lymphocytes (PBLs). The cells were stimulated with various cytokines or 12-O-tetradecanoyl phorbol 13-acetate (PMA) plus ionomycin, About 30% of unstimulated PBLs expressed Fas, and the expression was augmented by interleukin-1 beta (IL-1 beta), IL-2, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), or PMA plus ionomycin. Although only minimal Past expression was detected on unstimulated PBLs, Fast expression was markedly induced by IL-2 or PMA plus ionomycin, suggesting that Pas and Past were both expressed on IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs. Although Ii-2-stimulated or PMA-plus-ionomycln-stimulated PBLs were positive for both Fas and FasL, no significant increase in apoptosis was demonstrated in these activated PBLs. In addition, treatment of PBLs with IL-2 or PMA plus ionomycin did not change anti-Pas-induced apoptosis, although these activated PBLs expressed Pas strongly when compared with unstimulated PBLs. Only IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs killed Fas(+) target cells efficiently via the interaction of Pas on target cells with Fas(+) of PBLs. Bcl-2 was constitutively expressed on unstimulated PBLs, but its expression was significantly augmented by IL-2 or PMA plus ionomycin. The expression of Bax was clearly induced only on Ii-2-stimulated or PMA-plus-ionomycin-stimulated PBLs and that of other Bcl-2 family proteins such as Bcl-x and Bad could not be detected on human PBLs, including IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs. Our results suggest that PBLs activated by IL-2 or PMA plus ionomycin express both Pas and Fast and that they kill Fas(+) target cells by using Fast on the surface. The resistance of these activated PBLs to Pas-mediated apoptosis may be due to the augmented Bcl-2 expression or the presence of Bcl-5:Bax heterodimers on these cells.