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 (Fas L) on peripheral blood lymphocytes (PBLs). The cells were stimulated w ith various cytokines or 12-O-tetradecanoyl phorbol 13-acetate (PMA) p lus ionomycin, About 30% of unstimulated PBLs expressed Fas, and the e xpression was augmented by interleukin-1 beta (IL-1 beta), IL-2, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), or P MA 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 o n IL-2-stimulated or PMA-plus-ionomycin-stimulated PBLs. Although Ii-2 -stimulated or PMA-plus-ionomycln-stimulated PBLs were positive for bo th 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 unstim ulated PBLs. Only IL-2-stimulated or PMA-plus-ionomycin-stimulated PBL s 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 b y IL-2 or PMA plus ionomycin. The expression of Bar was clearly induce d only on Ii-2-stimulated or PMA-plus-ionomycin-stimulated PBLs and th at of other Bcl-2 family proteins such as Bcl-x and Bad could not be d etected on human PBLs, including IL-2-stimulated or PMA-plus-ionomycin -stimulated PBLs, Our results suggest that PBLs activated by IL-2 or P MA plus ionomycin express both Pas and Fast and that they kill Fas(+) target cells by using Fast on the surface, The resistance of these act ivated 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.