Induction of Granulomatous Experimental Autoimmune Thyroiditis in IL-4 Gene-Disrupted Mice

Abstract

To study the role of IL-4 in development of granulomatous experimental autoimmune thyroiditis (EAT), IL-4 gene-disrupted mice expressing the EAT-susceptible H-2k haplotype were generated and used for EAT induction. Spleen cells from mouse thyroglobulin (MTg) and LPS-primed IL-4+/+ and IL-4−/− donors could induce severe granulomatous EAT when spleen cells were activated with MTg and anti-IL-2R mAb in the presence of IL-12. Thyroid lesions had extensive follicular cell proliferation, large numbers of histiocytes, polymorphonuclear leukocytes, and multinucleated giant cells, in addition to lymphocytes and other mononuclear cells. Expression of IFN-γ gene mRNA and production of IFN-γ by effector spleen cells stimulated with MTg and IL-12 were similar for both IL-4+/+ and IL-4−/− mice. Although IL-4 was undetectable in IL-4−/− mice, expression of mRNA for IL-5, IL-10, and IL-13 and production of IL-5 by both MTg-activated spleen cells and anti-CD3-activated CD4+ T cells were comparable for cells from IL-4+/+ and IL-4−/− mice, indicating that the absence of IL-4 did not prevent production of other Th2 cytokines. Production of MTg-specific IgG1 was very low or undetectable in IL-4−/− mice. IL-4 gene mRNA and MTg-specific IgG1 could be detected in IL-4+/+ or IL-4−/− recipients only when they received effector cells from IL-4+/+ donor mice, indicating that IL-4- and IgG1-secreting cells are of donor origin. These results demonstrate that IL-4 is not essential for development of granulomatous EAT.