γδ T Cell Receptor Deficiency Attenuated Cardiac Allograft Vasculopathy and Promoted Regulatory T cell Expansion

Abstract

γδ T cell comprises about 5% of the overall T cell population, and they differ from conventional αβ T cells. Previous studies have indicated the contribution of γδ T cell to acute allograft rejection, but the role of γδ T cell in cardiac allograft vasculopathy (CAV) is not investigated. Hearts of adult B6.C-H-2(bm12) KhEg were heterotopically transplanted into major histocompatibility complex (MHC) class II-mismatched C57BL/6 mice (wild-type, γδ TCR(-/-)), which is an established murine model of chronic allograft rejection without immunosuppression. The survival of grafts was monitored daily by abdominal palpation until the complete cessation of cardiac contractility. Our current study demonstrated that γδ T cell receptor (TCR) deficiency significantly attenuated CAV, and this effect coincides with low expression of Hmgb1, IFN-γ and IL-17 while increased number of CD4(+) CD25(+) Foxp3(+) regulatory T cells, and depletion of regulatory T cells abrogated the prolonged allograft survival induced by γδ TCR deficiency. γδ TCR deficiency resulted in attenuated CAV and prolonged graft survival in murine models of cardiac transplantation, and this effect was associated with enhanced expansion of regulatory T cells.