Protein kinase Ctheta controls Th1 cells in experimental autoimmune encephalomyelitis |
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Authors: | Salek-Ardakani Shahram So Takanori Halteman Beth S Altman Amnon Croft Michael |
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Institution: | Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA. |
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Abstract: | Molecules that regulate encephalitogenic T cells are of interest for multiple sclerosis. In this study we show that protein kinase Ctheta (PKCtheta) is critical for the development of Ag-specific Th1 cells in experimental allergic encephalomyelitis (EAE), a model of multiple sclerosis. PKCtheta-deficient mice immunized with myelin oligodendrocyte glycoprotein failed to develop cell infiltrates and Th1 cytokines in the CNS and were resistant to the development of clinical EAE. CD4 T cells became primed and accumulated in secondary lymphoid organs in the absence of PKCtheta, but had severely diminished IFN-gamma, TNF, and IL-17 production. Increasing Ag exposure and inflammatory conditions failed to induce EAE in PKCtheta-deficient mice, showing a profound defect in the myelin oligodendrocyte glycoprotein-reactive T cell population. These data provide evidence of a pivotal role for PKCtheta in the generation and effector function of autoimmune Th1 cells. |
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