Endogenous IL-12 is required for induction and expression of experimental autoimmune uveitis
Pathogenic T cells involved in experimental autoimmune uveitis (EAU) are thought to be Th1-like. However, IFN-γ deficient (GKO) mice develop EAU in the context of an effector response having many elements of a Th2-like cytokine profile. IL-12 promotes Th1 responses. We, therefore, investigated whether IL-12 is required for development of EAU. IL-12 deficient mice (12KO) were highly resistant to EAU induced with the uveitogenic retinal antigen IRBP. Delayed-type hypersensitivity to IRBP was reduced, whereas antigen-specific proliferation in culture was strongly enhanced. Primed lymphocytes of wild type (WT) mice, cultured with IRBP, produced a Th1-like cytokine profile (high IFN-γ, low IL-5 and IL-10) and transferred EAU to syngeneic WT recipients. The same cells were less efficient in transferring EAU to 12KO recipients, unless IL-12 was included in the culture. Primed cells of 12KO mice produced a more Th2-like cytokine profile, similar to that of GKO mice (low IFN-γ, high IL-5 and IL-10), and failed to adoptively transfer EAU. However, when IL-12 was added to the culture, 12KO cells produced large amounts of IFN-γ 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 cytokine responses to GKO 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 suggests a role for endogenous IL-12 in the efferent phase of disease expression.
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Related Subject Headings
- Biochemistry & Molecular Biology
- 3208 Medical physiology
- 3101 Biochemistry and cell biology
- 1116 Medical Physiology
- 0606 Physiology
- 0601 Biochemistry and Cell Biology
Citation
Published In
ISSN
Publication Date
Volume
Issue
Related Subject Headings
- Biochemistry & Molecular Biology
- 3208 Medical physiology
- 3101 Biochemistry and cell biology
- 1116 Medical Physiology
- 0606 Physiology
- 0601 Biochemistry and Cell Biology