Activation of invariant NKT cells ameliorates experimental ocular autoimmunity by a mechanism involving innate IFN-gamma production and dampening of the adaptive Th1 and Th17 responses.

Activation of Invariant NKT Cells Ameliorates Experimental Ocular Autoimmunity by A Mechanism Involving Innate IFN- Production and Dampening of the Adaptive Th1 and Th17 Responses

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 EA...

P170: The Role of Th1 Lymphocytes in The Pathogenesis of Multiple Sclerosis (MS)

Th1 lymphocytes produce cytokines such as IL-2, IFN-γ, and TNF-α, TNF-β and GM-CSF. IFN-γ is the most important Th1 cell cytokine that induces the production of IgG, activation of macrophages, enhancing phagocytosis, and also increasing MHC class I and class II molecules. Increasing serum level of Th1 cytokines have also been observed in MS patients. It has also been prov...

Direct CD1d-mediated stimulation of APC IL-12 production and protective immune response to virus infection in vivo.

CD1d-restricted NKT cells rapidly stimulate innate and adaptive immunity through production of Th1 and/or Th2 cytokines and induction of CD1d(+) APC maturation. However, therapeutic exploitation of NKT cells has been hampered by their paucity and defects in human disease. NKT cell-APC interactions can be modeled by direct stimulation of human APCs through CD1d in vitro. We have now found that d...

Secretion of IFN-gamma but not IL-17 by CD1d-restricted NKT cells enhances rejection of skin grafts expressing epithelial cell-derived antigen.

NKT cells are key regulators of autoimmunity, tumor immune surveillance, and the immune response to pathogens. The role of NKT cells in regulating adaptive immunity to cutaneous Ags is largely unknown. This study explores the role of CD1d-restricted NKT cells in cross-priming of CD8 effector T cells to OVA expressed in epithelial keratinocytes (K5mOVA transgenic mouse). In a skin grafting model...