Immune response to intraocular injection of retinal S-antigen in adjuvant

Abstract

It has been proposed that the introduction of foreign material into the eye at the moment of a penetrating trauma provides an adjuvant effect which, coupled with the release of antigen, might be responsible for sensitizing the immune system to produce a contralateral "sympathetic ophthalmia." We addressed that hypothesis by injecting S-antigen with complete Freund's adjuvant (CFA) into the anterior chamber (AC) of the eye of Lewis rats. The injection of an identical dose of antigen (30 micrograms S-Ag in CFA in a total volume of 10 microliters) via the foodpad (FP) or under the conjunctiva (SC) could induce typical experimental autoimmune uveitis (EAU). By immunizing via the AC route, we could demonstrate a positive sensitization of the immune system, manifested by serum antibody production against S-Ag and by the presence of S-Ag-specific, responsive T-lymphocytes in the spleen. However, immunization via the AC route did not induce contralateral uveitis, and the animals did not produce a DTH skin response when challenged intradermally with S-Ag as they did after FP immunization. In the light of these results, we evaluated the possibility that a DTH suppressive response was elicited by intracameral (IC) injection as seen in anterior chamber-associated immune deviation (ACAID): we tested the effect of splenectomy and cyclophosphamide pretreatment before IC immunization and the effect of secondary footpad immunization as well as T-helper cell transfer after IC immunization. The results given by these approaches argue against the induction of suppressor cells by IC immunization.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulatory T Cells Control Uveoretinitis Induced by Pathogenic Th1 Cells Reacting to a Specific Retinal Neoantigen

“…In classical models of EAU, the disease was induced by immunization with a retinal Ag (42,43). However, our model of uveitis could not be obtained simply by immunization with the HA peptide emulsified in CFA in recipient mice expressing HA in their retina (not shown).…”

Association of a PDCD1 Polymorphism With Sympathetic Ophthalmia in Han Chinese

“…SO is a sight threatening panuveitis and is thought to be mediated by an immune response against a broad range of ocular antigens, although the exact antigens remain to be identified. 28 In contrast to VKH, the autoimmune response in SO may not only be confined to melanocyte associated antigens, 5 but may also involve a T cell-mediated immune response to retinal photoreceptor antigens, such as S antigen 3 and IRBP. 4 This hypothesis is mainly based on the findings in experimental models of uveitis whereby immunization of animals with these antigens can cause ocular disease that resembles SO in humans.…”

“…4 This hypothesis is mainly based on the findings in experimental models of uveitis whereby immunization of animals with these antigens can cause ocular disease that resembles SO in humans. [3][4][5] The fact that VKH is associated with many more immune response genes than SO may be due to the fact that SO is an autoimmune disease directed against a broader range of autoantigens than VKH. Many studies on the pathogenesis of SO have focused on the role of cytokines.…”

“…Although the pathogenesis and etiology of SO is not fully understood, SO has been postulated to be a T cell-mediated autoimmune response directed to ocular self-antigens, such as S antigen, interphotoreceptor retinoid binding protein (IRBP), and melanocyte associated antigens. [3][4][5] Genetic factors play a role in the pathogenesis of SO whereby associations have been reported with genes encoded by the human leukocyte antigen (HLA) system. Associations have been reported with HLA-DR4, 6 HLA-DRB1*04, HLA-DQA1*03, 7 and HLA-A11 8 genotypes in Japanese and European patients.…”

Intraocular Diseases – Anterior Uveitis

“…The clinical importance of AC-associated immune deviation is unknown; however, animals immunized through the AC with retinal autoantigens (e.g. S-antigen or interphotoreceptor retinoid binding protein) are protected from experimental autoimmune uveitis [46,47]. Suppression of immunological responsiveness by single or multiple doses of autoantigens via oral, intranasal and intravenous routes has been demonstrated to suppress uveitis in rodent models [48][49][50][51].…”