Residues 1-20 of IRBP and whole IRBP elicit different uveitogenic and immunological responses in interferon gamma deficient mice

Experimental autoimmune uveoretinitis (EAU) is a T-cell-mediated autoimmune disease induced by immunization with uveitogenic retinal antigens, or by t he adoptive transfer of uveitogenic T-cells of the Th-l-like phenotype. We have previously shown that IFN-gamma-deficient mice (GKO) on the C57BL/6 ba ckground are equally susceptible to interphotoreceptor retinoid binding pro tein (IRBP)-induced EAU as the wild type (WT). In the present study, we eva luated EAU induction in GKO mice by the newly described 11-2(b) epitope con tained in residues 1-20 of human IRBP, and compared it to the response to t he whole IRBP molecule. Similarly to previous observations with IRBP-induce d EAU, delayed type hypersensitivity (DTH) and lymphocyte proliferation res ponses were elevated in GKO mice, as was production of IL-5 and TNF-alpha. However unlike the responses induced by whole IRBP, there was no delectable IL-IO production to the peptide. Histopathology on day 21 after immunizati on. revealed that both GKO and WT mice developed retinal lesions, including damage to the photoreceptor cell layer, vasculitis and inflammatory cellul ar infiltration, but disease scores were significantly higher in GKO, and r etinal detachment was observed only in GKO mice. In contrast to the wild ty pe, the cellular infiltrate in eyes of GKO mice contained a prominent compo nent of eosinophils, although of lower proportion in peptide-induced than i n IRBP-induced EAU. We conclude that the cytokine and inflammatory response s to human peptide 1-20 differ perceptibly from the responses to whole bovi ne IRBP, and may explain the elevated EAU scores of GKO mice compared to wi ld type.