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Laboratory of Immunology and
Laboratory of Retinal Cell and Molecular Biology, the National Eye Institute, and the
Howard Hughes Medical Institute-National Institutes of Health Research Scholars Program, National Institutes of Health, Bethesda, MD 20892
Experimental autoimmune uveitis (EAU) has been associated with a
Th1 response. However, in IFN-
-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- 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--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.
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