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.
Wimmer et al. (Fri,) studied this question.