| First Author | Tarrant TK | Year | 1998 |
| Journal | J Immunol | Volume | 161 |
| Issue | 1 | Pages | 122-7 |
| PubMed ID | 9647215 | Mgi Jnum | J:119208 |
| Mgi Id | MGI:3701541 | Doi | 10.4049/jimmunol.161.1.122 |
| Citation | Tarrant TK, et al. (1998) Endogenous IL-12 is required for induction and expression of experimental autoimmune uveitis. J Immunol 161(1):122-7 |
| abstractText | Experimental autoimmune uveitis (EAU) has been associated with a Th1 response. However, in IFN-gamma-deficient mice, EAU develops in the context of an effector response having Th2-like elements, and administration of IL-12 to mice immunized for EAU induction can be protective. We, therefore, investigated whether endogenous IL-12 is required for development of EAU. IL-12 p40-deficient mice (12KO) were resistant to EAU induced with the uveitogenic retinal Ag interphotoreceptor retinoid binding protein (IRBP). Delayed hypersensitivity to IRBP was marginally reduced, whereas Ag-specific proliferation was enhanced. Primed lymphocytes of wild-type (wt) mice, cultured with IRBP, produced a Th1-like cytokine profile and transferred EAU to syngeneic wt recipients. Interestingly, the same cells were inefficient in transferring EAU to 12KO recipients, unless IL-12 was included in the culture. Primed cells of the 12KO mice produced a Th2-like cytokine profile and failed to transfer EAU. However, when IL-12 was added to the culture, 12KO cells produced large amounts of IFN-gamma and transferred EAU to naive 12KO recipients. We conclude that resistance to EAU of 12KO mice is not due to an inherent inability of these mice to develop ocular disease. Despite an apparent similarity in Ag-specific cytokine responses to IFN-gamma-deficient mice, 12KO mice have inhibited generation of uveitogenic effector cells, a situation that can be reversed even after priming, by adding exogenous IL-12 ex vivo. Lastly, the diminished ability of primed wt lymphocytes to induce EAU in 12KO mice indicates a role for endogenous IL-12 in the efferent phase of disease expression that is distinct from its role during Ag priming. |
