Functional significance of adhesion molecules in Fas-dependent apoptotic cell death induced by...

We investigated the functional significance of the adhesion molecules CD2 and lymphocyte function-associated antigen-1 (LFA-1: CD11a/CD18) in Fas-Fas ligand (FasL) death pathway. Interleukin-2-activated T cells expressed a large amount of FasL protein and could efficiently kill a Fas-sensitive leukemic cell line, MML-1. The major part (over 80%) of MML-1 cell death was Fas-dependent. Antibodies to CD2 and CD11a/CD18 completely inhibited MML-1 target cell lysis, whereas effector to target cell binding was partially reduced or not affected at all. These results suggest that effector/target interaction via CD2/CD58 and LFA-1/CD54 systems would be essential for triggering target cell death. More interestingly, there is the discordance in the ability of anti-CD2, and particularly anti-LFA-1 antibodies, to block Fas-dependent cell death versus effector to target conjugate formation. This suggests some non-adhesive role for CD2 and LFA-1 in induction of Fas-dependent cell death. Although these antibodies were capable of inhibiting T cell proliferative response, there was no significant reduction of FasL or granzyme B expression. Thus, the signaling pathway for growth inhibition via CD2 and LFA-1 could not be linked to signaling for FasL and granzyme B expression.