Protein kinase Ctheta controls Th1 cells in experimental autoimmune encephalomyelitis.
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.
Salek-Ardakani
Shahram
S
Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
So
Takanori
T
Halteman
Beth S
BS
Altman
Amnon
A
Croft
Michael
M
D000818:Animals; D001921:Brain / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology; D007527:Isoenzymes / Q000172:deficiency* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D011493:Protein Kinase C / Q000172:deficiency* / Q000276:immunology; D000074121:Protein Kinase C-theta; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D020381:Interleukin-17; D007527:Isoenzymes; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; C489593:Prkcq protein, mouse; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta