TRIGGERING VIA THE ALTERNATIVE CD2 PATHWAY INDUCES APOPTOSIS IN ACTIVATED HUMAN T-LYMPHOCYTES

Activation of immature thymocytes or transformed (i.e. leukemic) T lym phocytes via CD3/T cell receptor (TcR) signaling can induce programmed cell death (apoptosis). Recent data indicate that anti-CD3/TcR monocl onal antibodies (mAb) also trigger apoptosis in activated (but not res ting) mature peripheral LT cells. We now report that interleukin-2 (IL -2) dependent human polyclonal T cell lines as well as T cell clones u ndergo programmed cell death when triggered via the alternative CD2-de pendent activation pathway. In the presence of exogenous IL-2, a pair of mitogenic anti-CD2 mAb suppressed the IL-2-driven proliferative res ponse. Growth inhibition was associated with cell death and DNA fragme ntation as revealed by propidium iodide staining and gel electrophores is, respectively. Induction of apoptosis by anti-CD2 mAb was prevented by cyclosporine A and FK 506. We conclude that programmed cell death can be initiated in activated human T cells by signaling via the CD2 p athway.