INDUCTION OF IMMUNOTOLERANCE IN RATS BY INTRATESTICULAR ADMINISTRATION OF AN EICOSAPEPTIDE OF BOVINE S-ANTIGEN

Immunization of albino LEW rats with a retinal soluble antigen (S-anti gen) induces experimental autoimmune uveoretinitis (EAU) which shows c linical features resembling those of human uveitis, Several uveitogeni c epitopes have been identified in the antigen, This study reports tha t an intratesticular injection of low doses of a uveitogenic eicosapep tide (P343-362) of S-antigen prior to immunization with the same pepti de prevented the onset of EAU by inducing systemic tolerance, designat ed orchidic tolerance, Splenic lymphocytes of both CD4(+) and CD8(+) s ubsets from tolerized rats transferred orchidic tolerance to syngeneic recipients and protected them from subsequent EAU induction, Orchidic tolerance elicited by low antigen dosage was mediated, in part, by ac tive suppression due to suppressor or regulatory cells, At high antige n doses, how ever, regulatory activity was reduced possibly due to the induction of anergy in regulatory cells, and EAU severity increased, The CD4(+) regulatory T cells from tolerized rats showed enhanced expr ession of IL-4 mRNA compared with CD4(+) cells from control rats, Incr eased immunoreactivity for IL-4, IL-10 and TGF-B was observed in the s pleen and lymph nodes of tolerized animals, The results suggest that o rchidic tolerance induced by low doses of P343-362 is mediated in part by CD4(+) regulatory cells secreting Th2 cytokines.