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

Tuberculosis (TB) is a chronic infectious disease caused by <i>Mycobacterium tuberculosis</i> 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 <i>Mtb</i>-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 <i>Mtb</i>, recent advances in TB vaccine research, and prospective directions for future investigation are synthesized in this review.