Fas/Fas-ligand interactions modulate immune privilege and immune deviation in the eye

Purpose. Fas/Fas-ligand interactions are an important component of immune privilege in the eye. The eye expresses FasL which induces apoptosis in invading inflammatory cells thereby preventing potentially damaging reactions near important ocular structures. Here we examine the role of Fas/FasL induced apoptosis in the induction of immune deviation. Methods. Balb/c, C57BL/6 (B6), B6-gld, or B6-lpr mice were injected in the anterior chamber (AC) with HSV-1 or TNP-spl. Mice were examined for immune deviation and the eyes were assessed for the presence of apoptotic cells by in situ terminal deoxytransferase-catalyzed DNA end labeling (TUNEL) stains. Results. B6 mice developed immune deviation to HSV-1, while lpr and gld mice did not. In B6 mice invading inflammatory cells underwent apoptosis in the eye, while inflammatory cells in the lpr and gld mice did not. We further investigated the role of Fas and FasL in TNP-spleen induced immune deviation. The induction of immune deviation required FasL expression in the eye, Fas expression on the injected cells, as well as apoptotic cell death of the injected cells. The essential nature of apoptosis for tolerance induction was confirmed when TNP-spl from B6-lpr, which did not induce ACAID when injected into B6 mice, did so when they were induced to undergo apoptosis prior to AC injection. Similarly, TNP-spl from transgenic animals overexpressing bcl-x in T cells and thereby can not undergo apoptosis, did not induce immune deviation. Conclusions. Our results suggest that Fas/FasL induced cell death is important in the maintenance of immune privilege and the induction of immune deviation.