Deficiency in Soluble FasL Terminates Ocular Immune Privilege to Promote Elimination of Intraocular Tumors

Abstract The eye is a site of immune privilege exemplified by the observation that immunogenic tumor cells, for example P815 mastocytomas, that are rejected when transplanted in the skin of Balb/C J mice, grow progressively forming intraocular tumors when placed in the anterior chamber (a.c.) of the eye. The mechanisms that promote and maintain ocular immune privilege are not completely understood. However, CD95/FasL has been shown to contribute to ocular immune privilege (Griffith TS et al. 1995. Science 270:1189) and is expressed as a membrane associated molecule that can be cleaved to generate a soluble form. To begin to evaluate whether membrane or soluble FasL was required for ocular immune privilege, P815 tumor growth was monitored in mice unable to generate soluble FasL (DCS mice) due to a point mutation introduced in the FasL cleavage site. Twenty-four days after tumor challenge in the a.c. of the eye, tumor burden, measured by weight of challenged eyes, was reduced 5-fold in DCS mice in comparison to wild-type mice (DCS: 99+/−34 mg vs. Balb C/J: 20+/−15mg) and this difference was statistically significant (p<0.0001) and reproducible. The weight of tumors in DCS mice was equivalent to control non tumor challenged eyes suggesting complete tumor elimination. These data suggest that soluble FasL is necessary to maintain ocular immune privilege and promote intraocular tumor growth.