Rejection of mesencephalic retinal xenografts in the rat induced by systemic administration of recombinant interferon-gamma.

Previous studies have shown that mesencephalic retinal xenografts can be induced to undergo rejection following various systemic and local manipulations of the host immune system. In each of these paradigms, the development of major histocompatibility complex (MHC) antigen expression on cells in and around the graft is correlated with the onset of rejection. We therefore examined the effect on graft viability of systemic administration of high-dose interferon-gamma a potent inducer of MHC antigen expression on cells within the brain. Postnatal Day 1 (P1) Sprague-Dawley rats received mesencephalic grafts of Embryonic Day 13 CD-1 mouse retina. Beginning at P30, one group of rats received daily injections of rat recombinant interferon-gamma intraperitoneally; litter-matched control animals received injections of vehicle alone. Rats were sacrificed on P51. Each of the animals with detectable grafts that had received interferon-gamma showed a strong rejection response characterized by perivascular cuffing with mononuclear cells in and around the graft and infiltration of the graft and the surrounding host brain by lymphocytes and MHC class I- and class II-antigen positive cells resembling reactive microglia. In contrast, only 2 of the 11 control grafts showed evidence of rejection. The rejection rate in the interferon-treated group was significantly higher than in the control group (Fisher's exact test, P = 0.0012). These results suggest that interferon-gamma is involved in the initiation and/or subsequent maintenance of the rejection response to cross-species transplants.