Differentiation of Th1 and Th2 cells in lymph nodes and spleens of mice during experimental autoimmune uveoretinitis.

PURPOSE Experimental autoimmune uveoretinitis (EAU) is a T-cell-mediated autoimmune disease that can be elicited in susceptible rodent strains by immunization with a retinal autoantigen, such as interphotoreceptor retinoid-binding protein (IRBP). In this study, we investigated whether there is a correlation between inflammation in the eye and T-helper (Th)1- and Th2-type responses in the lymph nodes and the spleen after immunization of B10.A mice with IRBP. METHODS B10.A mice were immunized with IRBP emulsified with complete Freund's adjuvant (CFA), and eyes were then enucleated for histological examination of EAU at 1, 2, 4, 6, or 8 weeks after immunization. In addition, lymph node cells and spleen cells were collected, and cultured with IRBP to measure T-cell proliferation responses and Th1-type (interleukin [IL]-2, interferon [IFN]-gamma), Th2-type (IL-4, IL-10) cytokine production. RESULTS Pathologically, severe ocular inflammation occurred 2 weeks after IRBP immunization, persisted for 2 weeks, and then gradually resolved. Interleukin-2 and IFN-gamma production were observed in draining lymph node cells at 1 and 2 weeks after IRBP immunization. Those responses then diminished, whereas IFN-gamma production by spleen cells was observed from week 1, peaked at week 4, and gradually decreased. Alternatively, significant production of IL-4 or IL-10 by draining lymph node cells was not detected at any time point. Both IL-4 and IL-10 production by spleen cells was observed at week 6. CONCLUSIONS Th1-type responses were observed early in draining lymph nodes, then in the spleen after IRBP immunization. The levels of IFN-gamma production by spleen cells reflected the severity of EAU, confirming their pathogenic role in this disease. Th2-type responses were generated in the spleen only as the disease receded, suggesting a role for Th2 cells in the spontaneous termination of EAU.