A Distinct Role of CD4^sup +^ Th17- and Th17-Stimulated CD8^sup +^ CTL in the Pathogenesis of Type 1 Diabetes and Experimental Autoimmune Encephalomyelitis

• Published in: Journal of clinical immunology 2011-10, Vol.31 (5), p.811
• Main Authors: Ankathatti Munegowda, Manjunatha, Deng, Yulin, Chibbar, Rajni, Xu, Qingyong, Freywald, Andrew, Mulligan, Sean J, van Drunen Littel-van den Hurk, Sylvia, Sun, Deming, Xiong, Sidong, Xiang, Jim
• Format: Article
• Language: English
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-011-9549-z

Both CD4^sup +^ Th17-cells and CD8^sup +^ cytotoxic T lymphocytes (CTLs) are involved in type 1 diabetes and experimental autoimmune encephalomyelitis (EAE). However, their relationship in pathogenesis of these autoimmune diseases is still elusive. We generated ovalbumin (OVA)- or myelin oligodendrocyte glycoprotein (MOG)-specific Th17 cells expressing RORγt and IL-17 by in vitro co-culturing OVA-pulsed and MOG^sub 35-55^ peptide-pulsed dendritic cells (DC^sub OVA^ and DC^sub MOG^) with CD4^sup +^ T cells derived from transgenic OTII and MOG-T cell receptor mice, respectively. We found that these Th17 cells when transferred into C57BL/6 mice stimulated OVA- and MOG-specific CTL responses, respectively. To assess the above question, we adoptively transferred OVA-specific Th17 cells into transgenic rat insulin promoter (RIP)-mOVA mice or RIP-mOVA mice treated with anti-CD8 antibody to deplete Th17-stimulated CD8^sup +^ T cells. We demonstrated that OVA-specific Th17-stimulated CTLs, but not Th17 cells themselves, induced diabetes in RIP-mOVA. We also transferred MOG-specific Th17 cells into C57BL/6 mice and H-2K^sup b-/-^ mice lacking of the ability to generate Th17-stimulated CTLs. We further found that MOG-specific Th17 cells, but not Th17-activated CTLs induced EAE in C57BL/6 mice. Taken together, our data indicate a distinct role of Th17 cells and Th17-stimulated CTLs in the pathogenesis of TID and EAE, which may have great impact on the overall understanding of Th17 cells in the pathogenesis of autoimmune diseases.[PUBLICATION ABSTRACT]