Potential of Vγ9Vδ2T cells in tuberculosis: integration of innate and adaptive immunity for vaccine development

Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis that poses major global health challenges. The Bacillus Calmette–Guérin (BCG) vaccine provides only limited protection against TB in adults and the current therapeutic regimens for TB are constrained by prolonged treatment cycles and the emergence of drug-resistant strains. Consequently, the role of Vγ9Vδ2 T cells in anti-TB immunity has increasingly garnered attention. These nonconventional T lymphocytes rapidly recognize Mtb -infected cells and exert effector functions through a unique T-cell receptor that directly recognizes phosphorylated antigens independent of the major histocompatibility complex. Vγ9Vδ2 T cells mediate direct cytotoxicity against infected cells and coordinate with other immune components to strengthen the host defense against TB. These distinctive attributes highlight the potential of Vγ9Vδ2 T cells as targets in novel TB vaccine strategies. The current understanding of Vγ9Vδ2 T cell-mediated immunity to Mtb , recent advances in TB vaccine research, and prospective directions for future investigation are synthesized in this review.