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

摘要

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.