IFN-γ and IL-17 production in experimental autoimmune encephalomyelitis depends on local APC–T cell complement production

J Liu, F Lin, MG Strainic, F An, RH Miller… - The Journal of …, 2008 - journals.aai.org
J Liu, F Lin, MG Strainic, F An, RH Miller, CZ Altuntas, PS Heeger, VK Tuohy, ME Medof
The Journal of Immunology, 2008journals.aai.org
Abstract IFN-γ-and IL-17-producing T cells autoreactive across myelin components are
central to the pathogenesis of multiple sclerosis. Using direct in vivo, adoptive transfer, and
in vitro systems, we show in this study that the generation of these effectors in myelin
oligodendrocyte glycoprotein 35–55-induced experimental autoimmune encephalomyelitis
depends on interactions of locally produced C3a/C5a with APC and T cell C3aR/C5aR. In
the absence of the cell surface C3/C5 convertase inhibitor decay-accelerating factor (DAF) …
Abstract
IFN-γ-and IL-17-producing T cells autoreactive across myelin components are central to the pathogenesis of multiple sclerosis. Using direct in vivo, adoptive transfer, and in vitro systems, we show in this study that the generation of these effectors in myelin oligodendrocyte glycoprotein 35–55-induced experimental autoimmune encephalomyelitis depends on interactions of locally produced C3a/C5a with APC and T cell C3aR/C5aR. In the absence of the cell surface C3/C5 convertase inhibitor decay-accelerating factor (DAF), but not the combined absence of DAF and C5aR and/or C3aR on APC and T cells, a heightened local autoimmune response occurs in which myelin destruction is markedly augmented in concert with markedly more IFN-γ+ and IL-17+ T cell generation. The augmented T cell response is due to increased IL-12 and IL-23 elaboration by APCs together with increased T cell expression of the receptors for each cytokine. The results apply to initial generation of the IL-17 phenotype because naive CD62L high Daf1−/− T cells produce 3-fold more IL-17 in response to TGF-β and IL-6, whereas CD62L high Daf1−/− C5aR−/− C3aR−/− T cells produce 4-fold less.
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