IL-21R expression on CD8+ T cells promotes CD8+ T cell activation in coxsackievirus B3 induced myocarditis

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• 作者：Wei Liu^a ; ^{doctor_Liuwei@yahoo.com.cn} ; Oliver Dienz^b ; ^{oliver.dienz@uvm.edu} ; Brian Roberts^b ; ^{brian.roberts@uvm.edu} ; Mohamad Moussawi^b ; ^{Mohamad.moussawi@uvm.edu} ; Mercedes Rincon^b ; ^{Mercedes.rincon@uvm.edu} ; Sally A. Huber^b ; ^{sally.huber@uvm.edu}
• 关键词：Coxsackievirus B3 ; Myocarditis ; IL-21R ; CD8 T cells ; Autoimmunity
• 刊名：Experimental and Molecular Pathology
• 出版年：2012
• 期刊代码：291_00144800
• 类别：med
• 出版时间：June, 2012
• 卷：92
• 期：3
• 页码：327-333
• 文件大小：1081 K

摘要

IL-21 is a multi-functional cytokine which can promote survival, proliferation and activation of T and B lymphocytes including CD8 T cells. Previous studies have shown that autoimmune CD8+ T cells are the primary pathogenic effector cell in coxsackievirus B3 (CVB3) induced myocarditis in C57Bl/6 mice. To evaluate the role of IL-21 in promoting CD8+ T cell mediated cardiac injury in myocarditis, C57Bl/6 and IL-21RKO mice were infected with CVB3. IL-21RKO mice developed significantly less myocarditis than C57Bl/6 animals although cardiac virus titers were equivalent between the mouse strains. Numbers of CD8+IFN纬+ cells were decreased in IL-21RKO mice but numbers of either CD4+IFN纬+ or CD4+IL-4+ cells were not significantly different from C57Bl/6 animals indicating a selective effect of IL-21 signaling on the CD8+ T cell response. To confirm that IL-21 signaling exclusively functions at the level of the CD8+ T cell in CVB3 induced myocarditis, purified CD8+ cells were isolated from either C57Bl/6 or IL-21RKO donors and adoptively transferred into CD8KO recipients prior to CVB3 infection. CD8KO recipients given either C57Bl/6 or IL-21RKO CD8+ cells showed equivalent reconstitution of the CD8+ cells in the spleen but the recipients given C57Bl/6 CD8+ cells showed significantly greater myocarditis than recipients of IL-21RKO CD8+ cells. These data demonstrate that IL-21 signaling directly in the CD8+ cell population is required for CVB3-induced myocarditis.