Abstract
Despite the identification of several mediators of arteriogenesis, the growth of natural bypass, the role of lymphocytes, particularly T cells, in this process remains poorly defined. Among these, γδ T cells, which express alternative T cell receptors, have emerged as a key immune component. This study examined the roles of αβ and γδ T cells in arteriogenesis using a murine hindlimb model. While the absence of αβ T cells did not affect arteriogenesis, γδ T cell depletion markedly reduced vascular cell proliferation and perfusion recovery. Early phase analyses revealed impaired mast cell activation, whereas platelet-neutrophil aggregates and neutrophil extravasation were unaffected. In the later proliferative phase, γδ T cell depletion hindered perivascular M2-like (MRC1(+)) macrophage accumulation. Flow cytometric analysis of whole blood in wildtype mice revealed a temporal shift in γδ T cell populations from a CD27(+)/CD39(-) phenotype, commonly associated with pro-inflammatory functions and IFNγ production, to CD39(+) phenotypes, which have been linked to anti-inflammatory properties and IL-10 production. In rescue experiments, administration of IFNγ to γδ T cell-depleted mice restored mast cell activation, whereas IL-10 treatment reestablished M2-like (MRC1(+)) macrophage accumulation. These findings collectively identify γδ T cells as critical regulators of both early and late phases of arteriogenesis through coordinated inflammatory and regenerative mechanisms.