title: Cross-regulation of T regulatory-cell response after coxsackievirus B3 infection by NKT and γδ T cells in the mouse.
abstract: Coxsackievirus B3 (CVB3) variants H3 and H310A1 differ by a single nonconserved amino acid in the VP2 capsid region. C57Bl/6 mice infected with the H3 virus develop myocarditis correlating with activation of T cells expressing the Vγ4 T cell receptor chain. Infecting mice with H310A1 activates natural killer T (NKT; mCD1d-tetramer(+) TCRβ(+)) cells, but not Vγ4 T cells, and fails to induce myocarditis. H310A1 infection preferentially activates M2 alternatively activated macrophage and CD4(+)FoxP3 (T regulatory) cells, whereas CD4(+)Th1 (IFN-γ(+)) cells are suppressed. By contrast, H3 virus infection activates M1 proinflammatory and CD4(+)Th1 cells, but not T regulatory cells. The M1 macrophage show significantly increased CD1d expression compared to M2 macrophage. The ability of NKT cells to suppress myocarditis was shown by adoptive transfer of purified NKT cells into H3-infected NKT knockout (Jα18 knockout) mice, which inhibited cardiac inflammation and increased T regulatory cell response. Cardiac virus titers were equivalent in all mouse strains indicating that neither Vγ4 nor NKT cells participate in control of virus infection. These data show that NKT and Vγ4 cells cross-regulate T regulatory cell responses during CVB3 infections and are the primary factor determining viral pathogenesis in this mouse model.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Mohamad
authors.initials: M
authors.lastname: Moussawi
authors.forename: Brian
authors.initials: B
authors.lastname: Roberts
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Boyson
authors.forename: Sally A
authors.initials: SA
authors.lastname: Huber
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003384:Coxsackievirus Infections / Q000276:immunology*; D029822:Enterovirus B, Human / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055611:Natural Killer T-Cells / Q000276:immunology* / Q000821:virology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000821:virology
chemical_list: D018949:Antigens, CD1