ANTERIOR-CHAMBER INOCULATION OF SPLENOCYTES WITHOUT FAS FAS-LIGAND INTERACTION PRIMES FOR A DELAYED-TYPE HYPERSENSITIVITY RESPONSE RATHER THAN INDUCING ANTERIOR CHAMBER-ASSOCIATED IMMUNE DEVIATION/

The inoculation of antigens into the anterior chamber (AC) of the eye induces an antigen-specific immune response that inhibits delayed-type hypersensitivity (DTH). This regulatory response is known as anterior chamber-associated immune deviation (ACAID). The ACAID response appea rs to be complex, as it can be elicited by a wide variety of soluble a nd cell-associated antigens, including foreign, self, tumor, and alloa ntigens. To evaluate the contribution of Fas/Fas ligand (FasL) interac tion to the induction of ACAID to alloantigens, gld and lpr mutant mic e were used in conjunction with normal C3H, MRL, and BALB/c mice. ACAI D was induced by inoculation of non-irradiated splenocytes from donor mice into the AC of various recipients. After 1 week, recipients were primed intradermally with donor splenocytes. One week later DTH was me asured by ear swelling. C3Hgld mutants lacking functional FasL did not develop ACAID after the AC inoculation of BALB/c splenocytes. Convers ely the AC inoculation sensitized these mutants. MRLlpr mutants, which lack Fas, developed ACAID following inoculation of BALB/c cells. AC i noculation of lpr splenocytes did not induce ACAID, but sensitized C3H recipients. Treatment of the AC inoculum with an anti-Fas antibody bl ocked ACAID induction in a transient manner, as the recipients develop ed ACAID later. These results show that interaction of the Fas and Fas L is required to induce ACAID to allogeneic cells. In the absence of F as expression on donor splenocytes, or FasL expression by the recipien t, AC inoculation primes for a DTH response rather than inducing ACAID .