FAS TRANSDUCES ACTIVATION SIGNALS IN NORMAL HUMAN T-LYMPHOCYTES

The Fas gene encodes a cell surface molecule that is a member of the t he nerve growth factor/tumor necrosis factor receptor family of protei ns and can mediate programmed cell death (apoptosis) in certain transf ormed cell lines. To characterize further the biological function of F as, particularly with regard to its function in normal cells, a panel of monoclonal antibodies (mabs) was generated against the extracellula r portion of human Fas. Some of these mAbs induced apoptosis in transf ormed cell lines expressing Fas, but only when immobilized on the cult ure vessel. One of the new Fas mAbs (M38) was used for studies on norm al lymphoid cells and found to stimulate the proliferation of purified human T cells and thymocytes when immobilized on culture wells along with CD3 antibody. T cell proliferation induced by Fas mAb was largely interleukin 2 independent and was demonstrated to be due to a direct effect on the precursor T cell. Thus, the data demonstrate that in add ition to a role in the induction of apoptosis in certain transformed c ell lines, the Fas protein may also play an important role in the acti vation and proliferation of normal T cells.