Invariant NKT cells producing IL-4 or IL-10, but not IFN-gamma, inhibit the Th1 response in experimental autoimmune encephalomyelitis, whereas none of these cells inhibits the Th17 response.

Experimental autoimmune encephalomyelitis (EAE) is mediated by Th1 and Th17 cells. Invariant NKT (iNKT) cells prevent EAE in an IL-4-, IL-10-, and IFN-γ-dependent manner. However, which of the iNKT cell-produced cytokines regulates the Th1 or Th17 response in EAE remains unclear. Wild-type B6 and Jα18(-/-) mice were immunized with MOG(35-55) peptide to address this issue. Clinical scores for EAE, IL-17, and IFN-γ transcript levels, and IL-17- or IFN-γ-expressing CD4(+) T cell percentages in the CNS and draining lymph nodes were higher in Jα18(-/-) than in B6 mice, but all of these parameters in the CNS were reduced by the adoptive transfer of wild-type or IFN-γ-deficient iNKT cells into the Jα18(-/-) mice before immunization. In contrast, adoptive transfer of IL-4- or IL-10-deficient iNKT cells into Jα18(-/-) mice decreased IL-17 transcript levels and the percentage of IL-17-expressing CD4(+) T cells in the CNS but did not affect clinical scores, IFN-γ transcript levels, or the percentage of IFN-γ-expressing CD4(+) T cells in the CNS. Taken together, IL-4- and IL-10-producing iNKT cells inhibit the Th1 cell response, but not the Th17 cell response, although wild-type iNKT cells suppress both the Th1 and Th17 responses in the CNS during EAE. Moreover, IFN-γ-producing iNKT cells have a minimal role in the regulation of the Th1 and Th17 responses in EAE.

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