CD1d expression on hemopoietic cells promotes CD4+ Th1 response in coxsackievirus B3 induced myocarditis.
Coxsackievirus B3 induced murine myocarditis depends upon CD1d expression and upon a population of CD1d-restricted Vgamma4+ T cells. Infection upregulates CD1d expression in CD4+ T cells. Bone marrow chimeras were made between BALB/c and BALB/c CD1d-/- mice and showed that CD1d expression in either hemopoietic and non-hemopoietic cells induces myocarditis, although CD1d expression on hemopoietic cells was more effective in increasing Vgamma4+ cell numbers and activation, and CD4+ IFNgamma+ cell response than CD1d expression on non-hemopoietic cells. Co-culture of enriched CD4+ cells from infected CD1d-/- and BALB/c mice with Vgamma4+ T cells demonstrated that the Vgamma4+ cells bias the CD4+ cell response to the Th1 phenotype through CD1d. Anti-CD1d antibody effectively blocked promotion of IFNgamma expression by the CD4+ cell population. These results show that Vgamma4+ cells modulate developing adaptive immunity through recognition of CD1d on CD4+ T cells, and that this interaction, more than Vgamma4+ cell interaction with infected cardiocytes, determines pathogenicity.
Huber
S A
SA
University of Vermont, Department of Pathology, 208 South Park Drive, Suite #2, Burlington, VT 05446, USA. Sally.Huber@uvm.edu
D000818:Animals; D018949:Antigens, CD1 / Q000378:metabolism*; D055610:Antigens, CD1d; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D029822:Enterovirus B, Human / Q000472:pathogenicity*; D006413:Hematopoietic System / Q000166:cytology* / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000276:immunology* / Q000821:virology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*
D018949:Antigens, CD1; D055610:Antigens, CD1d; D016692:Receptors, Antigen, T-Cell, gamma-delta