γδ T lymphocytes kill T regulatory cells through CD1d

Area of Science:

• Immunology
• Virology
• Cardiovascular Research

Background:

• Coxsackievirus B3 (CVB3) infection causes myocarditis in C57Bl/6 mice, but not in gamma delta T cell knockout (γδKO) mice.
• Myocarditis suppression in γδKO mice correlates with increased CD4(+) CD25(+) FoxP3(+) T regulatory cells, some expressing CD1d.
• CD1d-expressing regulatory T cells are more suppressive than CD1d-negative counterparts.

Purpose of the Study:

• To investigate the role of γδ+ T cells in CVB3-induced myocarditis.
• To elucidate the mechanism by which γδ+ T cells influence T regulatory cells during viral myocarditis.

Main Methods:

• Utilized γδKO and wild-type C57Bl/6 mice models for CVB3 infection.
• Performed adoptive transfer of regulatory T cell subpopulations (CD1d+ and CD1d-).
• Analyzed γδ+ T cell populations, including Vγ4+ T cell receptor expression, and their cytotoxic activity against regulatory T cells.

Main Results:

• Vγ4+ γδ+ T cells, comprising 30-50% of heart-infiltrating cells in myocarditic mice, express the Vγ4 T-cell receptor.
• Vγ4+ γδ+ T cells lyse CD1d-expressing regulatory T cells from γδKO mice, but not from wild-type mice.
• This lysis is CD1d-dependent and caspase-mediated, and Vγ4-γδ+ T cells do not promote myocarditis.

Conclusions:

• Vγ4+ γδ+ T cells selectively eliminate CD1d-expressing regulatory T cells through CD1d recognition and caspase-dependent apoptosis.
• This selective abrogation of T regulatory cells by Vγ4+ γδ+ T cells contributes to the pathogenesis of CVB3-induced myocarditis.