CD95-INDUCED APOPTOSIS OF LYMPHOCYTES IN AN IMMUNE PRIVILEGED SITE INDUCES IMMUNOLOGICAL-TOLERANCE

We examined the relationship between cell death and tolerance inductio n following antigen injection into the anterior chamber of the eye. Ou r data show that when inflammatory cells undergo apoptosis following i nfection with HSV-1, tolerance to the virus was observed. In contrast, when cell death was absent due to defects in Fas or FasL, immune tole rance was not observed. Further studies revealed that cell death and t olerance required that the lymphoid cells be Fas(+) and the eye be Fas L(+). Additionally, we show that while Fas/FasL-mediated apoptosis occ urred in the eye, it was apoptotic cell death that was critical for to lerance induction. Our results further demonstrate immune privilege is not a passive process involving physical barriers, but is an active p rocess that employs an important natural mechanism to induce cell deat h and immune tolerance.