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 Vγ4+ 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 Vγ4+ cell numbers and activation, and CD4+ IFNγ+ cell response than CD1d expression on non-hemopoietic cells. Co-culture of enriched CD4+ cells from infected CD1d−/− and BALB/c mice with Vγ4+ T cells demonstrated that the Vγ4+ cells bias the CD4+ cell response to the Th1 phenotype through CD1d. Anti-CD1d antibody effectively blocked promotion of IFNγ expression by the CD4+ cell population. These results show that Vγ4+ cells modulate developing adaptive immunity through recognition of CD1d on CD4+ T cells, and that this interaction, more than Vγ4+ cell interaction with infected cardiocytes, determines pathogenicity.