Protective immune responses of major Vγ2Vδ2 T-cell subset in M. tuberculosis infection

Recent observation that prenyl pyrophosphates bind the Ig superfamily protein butyrophilin 3A1 (BTN3A1) suggests that modifying BTN3A1 activates major γδ T-cell subset, Vγ2Vδ2 T cells. Studies also show that microbial phosphoantigen HMBPP is required for expansion, pulmonary response, effector functions and memory polarization of Vγ2Vδ2 T cells during infections. Broad repertoires of cytokines involve expansion, recall-like expansion and effector functions of Vγ2Vδ2 T cells after Mtb infection or vaccination. Finally, mechanistic studies in nonhuman primate TB model demonstrate early expansion and differentiation of Vγ2Vδ2 T cells during Mtb infection can increase immune resistance to TB in macaques, with a potential mechanism of early/sustained IFN-γ production and CTL killing.