title: 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.
abstract: 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.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea.
authors.forename: Sae Jin
authors.initials: SJ
authors.lastname: Oh
authors.forename: Doo Hyun
authors.initials: DH
authors.lastname: Chung
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis*; D015847:Interleukin-4 / Q000096:biosynthesis*; D051379:Mice; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; C556062:IL10 protein, mouse; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma