CD95-induced apoptosis of lymphocytes in an immune privileged site induces immunological tolerance

We examined the relationship between cell death and tolerance induction following antigen injection into the anterior chamber of the eye. Our data show that when inflammatory cells undergo apoptosis following infection with HSV-1, tolerance to the virus was observed. In contrast, when cell death was absent due to defects in Fas or Fast, immune tolerance was not observed. Further studies revealed that cell death and tolerance required that the lymphoid cells be Fas⁺ and the eye be FasL. Additionally, we show that while Fas/FasL-mediated apoptosis occurred in the eye, it was apoptotic cell death that was critical for tolerance induction. Our results further demonstrate immune privilege is not a passive process involving physical barriers, but is an active process that employs an important natural mechanism to induce cell death and immune tolerance.