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 a utoimmune disease that can be elicited in susceptible rodent strains by imm unization with a retinal autoantigen, such as interphotoreceptor retinoid-b inding protein (IRBP). In this study, we investigated whether there is a co rrelation 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 mic e with IRBP. Methods: B10.A mice were immunized with IRBP emulsified with complete Freun d's adjuvant (CFA), and eyes were then enucleated for histological examinat ion 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 meas ure T-cell proliferation responses and Th1-type (interleukin [IL]-2, interf eron [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. Inte rleukin-2 and IFN-gamma production were observed in draining lymph node cel ls at 1 and 2 weeks after IRBP immunization. Those responses then diminishe d. whereas IFN-gamma production by spleen cells was observed from week 1, p eaked at week 4. and gradually decreased. Alternatively, significant produc tion 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 produ ction by spleen cells reflected the severity of EAU, confirming their patho genic 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 sponta neous termination of EAU. Jpn J Ophthalmol 2001;45:463-469 (C) 2001 Japanes e Ophthalmological Society.