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Updated: Jul 27, 2026
Isolation and Identification of Extravascular Immune Cells of the Heart
Published on: August 23, 2018
CD1d expression on hemopoietic cells promotes CD4+ Th1 response in coxsackievirus B3 induced myocarditis
1University of Vermont, Department of Pathology, 208 South Park Drive, Suite #2, Burlington, VT 05446, USA. Sally.Huber@uvm.edu
Insights
Coxsackievirus B3 myocarditis requires CD1d expression and specific T cells. CD1d on immune cells enhances this response, showing T cell interaction with CD1d on other immune cells drives disease.
Area of Science:
- Immunology
- Virology
- Cardiovascular Research
Background:
- Coxsackievirus B3 (CVB3) is a significant cause of viral myocarditis.
- The role of CD1d-restricted T cells in viral myocarditis pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of CD1d expression and CD1d-restricted Vgamma4+ T cells in CVB3-induced murine myocarditis.
- To elucidate the mechanism by which Vgamma4+ T cells influence adaptive immunity during CVB3 infection.
Main Methods:
- Generation of bone marrow chimeras between BALB/c and CD1d-/- mice.
- Co-culture experiments with T cell populations.
- Assessment of immune cell activation and cytokine production (IFN-gamma).
- In vivo blockade of CD1d interaction using antibodies.
Main Results:
- CD1d expression on both hematopoietic and non-hematopoietic cells contributed to myocarditis development.
- CD1d expression on hematopoietic cells more significantly increased Vgamma4+ T cell numbers and activation.
- Vgamma4+ T cells, via CD1d recognition on CD4+ T cells, biased CD4+ T cell response towards a Th1 phenotype.
- Anti-CD1d antibody treatment blocked IFN-gamma production by CD4+ cells.
Conclusions:
- Vgamma4+ T cells modulate adaptive immunity by recognizing CD1d expressed on CD4+ T cells.
- This interaction, rather than direct interaction with infected cardiomyocytes, is critical for CVB3 myocarditis pathogenicity.
- CD1d-mediated immune regulation plays a key role in the host response to CVB3 infection.
Abstract:
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.
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