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 surface antigens on T lymphocytes. Incubation of Fas-sensitive Jurkat (JM) cells with agonistic anti-Fas mAb induced rapid (within 4 hr) downmodulation of L-selectin (CD62L) and CD7 but not of CD3 or CD71. No modulation was observed on Fas-expressing but Fas-resistant JM variant 432.1. On PHA-activated, Fas-sensitive T cell blasts, anti-Fas mAb rapidly triggered downmodulation of a variety of antigens, including CD2, CD4, CD8, CD7, CD44, LFA1α, LFA1β, and CD62L, but not CD3, CD25, or CD26. Most of these antigens were not downmodulated by either CD3 crosslinking (except CD3) or PMA treatment (except CD3, CD4, and CD62L). Comparable patterns of biphasic CD44, LFA1α, and LFA1β expression were observed on CD4+and CD8+T cell blasts in response to Fas crosslinking. In these instances, downregulation occurred preferentially on cells undergoing rapid shrinkage. These results indicate that rapid downregulation of selected surface antigens is an early response of both normal and transformed T cells to Fas crosslinking.