The role of costimulatory molecules B7-1 and B7-2 in mice with experimental autoimmune uveoretinitis

Abstract

Onset of experimental autoimmune uveoretinitis (EAU) is believed to involve a CD4-positive type 1 T helper cell (Th1) immune response, with inhibition involving a Th2 immune response. Development of Th1 and Th2 responses involves the participation of the costimulatory molecules B7-1 and B7-2, respectively. The purpose of this study was to investigate the role of B7-1 and B7-2 in the EAU model in mice. B10.A mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) and given daily intraperitoneal injections of either phosphate-buffered saline (control), mouse monoclonal antibody (mAb) to B7-1, mAb to B7-2, or mAb to both B7-1 and B7-2. Eyes were evaluated by histopathological criteria and cytokines were assayed in culture medium of IRBP-stimulated lymphocytes. Cellular immune responses were measured by cell proliferation assay under IRBP stimulation. Rates of EAU onset were 5/10 (50%) for control mice, 1/9 (11%) for mice treated with anti-B7-1 mAb, 5/6 (83%) for mice treated with anti-B7-2 mAb, and 2/6 (33%) for mice treated with both anti-B7-1 and anti-B7-2 mAb. Mean histopathological severity scores were 2. 4+/-0.8, 1.0+/-0, 2.6+/-1.0, and 1.0+/-0, respectively. Production of IL-5 was significantly increased in mice treated with anti-B7-1 mAb, while IFN-gamma was increased in mice treated with anti-B7-2 mAb. Spleen cell proliferation was significantly reduced in mice treated with anti-B7-1 mAb. These results suggest that the costimulatory molecules B7-1 and B7-2, via their influence on generating Th1 and Th2 immune responses, play an important role in the clinical outcome of EAU in mice immunized with IRBP.