An Immunologically Privileged Retinal Antigen Elicits Tolerance

• DOI: 10.1084/jem.20030413
• Publication Date: 2003-12-02T00:03:18Z
• Authors: Dody Avichezer; Rafael S. Grajewski; Chi-Chao Chan; Mary J. Mattapallil; Phyllis B. Silver; James A. Raber; Gregory I. Liou; Barbara Wiggert; Giavonni M. Lewis; Larry A. Donoso; Rachel R. Caspi
• Keywords: Mice, Knockout; 0301 basic medicine; 570; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes; Article; Retina; Autoimmune Diseases; 3. Good health; Retinol-Binding Proteins; Mice; 03 medical and health sciences; Retinal Diseases; Immune Tolerance; Animals; Antigens; Eye Proteins

Immunologically privileged retinal antigens can serve as targets of experimental autoimmune uveitis (EAU), a model for human uveitis. The tolerance status susceptible strains, whose target antigen is not expressed in the thymus at detectable levels, unclear. Here, we address this issue directly by analyzing consequences genetic deficiency versus sufficiency uveitogenic antigen, interphotoreceptor retinoid-binding protein (IRBP). IRBP-knockout (KO) and wild-type (WT) mice on highly EAU-susceptible background were challenged with IRBP. KO had greatly elevated responses to IRBP, an altered recognition IRBP epitopes, their primed T cells induced exacerbated disease WT recipients. Ultrasensitive immunohistochemical staining visualized sparse IRBP-positive cells, undetectable conventional assays, thymi (but KO) mice. message was PCR amplified from these after microdissection. Thymus transplantation between hosts demonstrated that level expression functionally relevant sets threshold immune (and autoimmune) reactivity. Namely, recipients generated reduced IRBP-specific responses, developed enhanced disease. Repertoire culling thymus-dependent CD25+ implicated effect. Thus, uveitis-susceptible individuals display significant which central mechanisms play prominent role.