Immunological analysis of orally induced tolerance to corneal alloantigens

Purpose. To analyze the immune functions of hosts orally tolerized with corneal alloantigns. Methods. CB6F1 (H-2^b/d) mice were immunized with heterotjpic C3H/Hej (H-^2k) corneal grafts. One week later, grafted ind normal CB6F1 mice were orally tolerized with ], 5, or 13 daily doses of C3H/Hej corneal endothelial cells conjugited with nontoxic B subunit of cholera toxin (CTB). Allospecifi; cytotoxic T lymphocyte (CTL), delayed-type hypersensitivity (DTH), and mixed lymphocyte responses (MLR) were assessed 24 hr after the 10th oral inoculum. Peyer's patch cells (PC) were stimulated in vitro with C3H/Hej lymphocytes and their secretion of interferon- (IFN) and transforming growth fa:tor- (TGF-) was assessed by ELISA and bioassay. Results. 10 jral doses of CTB-conjugated corneal cells produced profound inhibition of allospecific CTL (70% reduction; P=0.001), DTH (85% reduction; P<0.001), and MLR (98% reduction; P<0.001). PPC fr>m mice fed CTB-conjugated corneal cells produced 60% less [FN- than PPC from normal mice (5 ng/ml vs. 2 ng/ml) but over tvice as much TGF- (94 pg/ml vs 38 pg/ml). Conclusions. Feeding :orneal alloantigens elicits orofound inhibition of cell-medi ited immunity and suooression of at least one pro inflammatory cytokine (IFN-γ).