Suppression of spontaneous uveoretinitis development by non-immunopathogenic peptide immunization.

BALB/c nude mice which are grafted with thymus tissue from fetal F344 rats beneath the renal capsule (hereafter referred to as TG nude mice) spontaneously develop uveoretinitis as well as other organ-localized autoimmune diseases. Active immunization with an interphotoreceptor retinoid-binding protein (IRBP)-derived peptide, amino acids 518-529 (P518-529), induced rapid development and high incidence of uveoretinitis, whereas immunization with another amino acid fragment, 1182-1194 (P1182-1194), inhibited the disease process. P1182-1194- or P518-529-specific T cell lines were established from TG nude mice. Although both were of CD4+ type, P518-529-specific T cells expressed Vbeta8 TCR while Vbeta6 expression was evident in the P1182-1194-specific cells. P518-529-specific T cells produced IL-2 and IFN-gamma, but not IL-4 or IL-10, whereas P1182-1194-specific T cells produced IL-4 and IL-10, but not IL-2 or IFN-gamma Adoptive transfer of these peptide-specific T cells into naive BALB/c nude mice resulted in development of uveoretinitis only in the P518-529 case. Furthermore, mice receiving both T cell types simultaneously did not exhibit uveoretinitis. The results indicate that the amino acid fragment of IRBP, P518-529, is uveitogenic and immunogenic in TG nude mice and induces Th1-type T cells related to uveoretinitis, whereas the amino acid fragment 1182-1194 is immunogenic but not uveitogenic, inducing Th2-type T cells which are involved in inhibition of this pathological response in TG nude mice.