RAPID MODULATION OF T-LYMPHOCYTE SURFACE-ANTIGENS INDUCED BY FAS (CD95, APO-1) LIGATION

Crosslinking the Fas (CD95, APO-1) antigen by mAb or Fas-ligand (Fas-L )-expressing cells triggers apoptosis. We have investigated the early consequences of Fas signaling on the expression of various cell surfac e antigens on T lymphocytes. Incubation of Fas-sensitive Jurkat (JM) c ells with agonistic anti-Fas mAb induced rapid (within 4 hr) downmodul ation of L-selectin (CD62L) and CD7 but not of CD3 or CD71. No modulat ion was observed on Fas-expressing but Fas-resistant JM variant 432.1. On PHA-activated, Fas-sensitive T cell blasts, anti-Fas mAb rapidly t riggered downmodulation of a variety of antigens, including CD2, CD4, CD8, CD7, CD44, LFA1 alpha, LFA1 beta, and CD62L, but not CD3, CD25, o r CD26. Most of these antigens were not downmodulated by either CD3 cr osslinking (except CD3) or PMA treatment (except CD3, CD4, and CD62L). Comparable patterns of biphasic CD44, LFA1 alpha, and LFA1 beta expre ssion were observed on CD4(+) and CD8(+) T cell blasts in response to Fas crosslinking. In these instances, downregulation occurred preferen tially on cells undergoing rapid shrinkage. These results indicate tha t rapid downregulation of selected surface antigens is an early respon se of both normal and transformed T cells to Fas crosslinking. (C) 199 6 Academic Press, Inc.