Stimulation through CD50 preferentially induces apoptosis of TCR1+ human peripheral blood lymphocytes

Apoptosis has an important role in several key immunological phenomena such as regulation of the immune response, and deletion of auto-reactive cells. This phenomenon is induced following the interaction of several cell membr ane receptors with their respective ligands or after cell activation, We ha ve studied the possible effect of signaling through CD50/ICAM-3 and CD69/AI M on apoptosis of peripheral blood lymphocytes, Apoptosis was assessed by b oth flow cytometry analysis (content of cell DNA and binding to annexin V), and detection of DNA fragmentation by agarose gel electrophoresis, We foun d that a stimulatory anti-CD50 mAb was able to induce a small but significa nt degree of apoptosis in resting peripheral blood mononuclear cells from m ost donors; this effect was dose-dependent and was evident as early as at 1 2 h, with a maximal induction at 45 h. Studies with T and non-T cells showe d that only the former cell population was sensitive to the induction of ap optosis through CD50, Further experiments revealed that the anti-ICAM-3 mAb preferentially induced apoptosis of TCR gamma delta-bearing cells. In addi tion, we found a significant increase in Ca-i(2+) in PBMC stimulated with a n anti-CD50 mAb, suggesting the involvement of this signaling pathway in th e induction of apoptosis through this adhesion receptor. In contrast, under our experimental conditions, stimulation through CD69 did not have any eff ect on the induction of apoptosis on either cultured T lymphoblasts or PMA- stimulated PBMC. Our findings suggest that the interaction of CD50 with its natural ligand LFA-I results in the induction of apoptosis in a significan t fraction of resting PBMC. This phenomenon may be involved in immune regul ation, lymphocyte turnover and peripheral deletion of auto-reactive cells.