Effector Functions of Conventional and Unconventional Mycobacterium tuberculosis (Mtb)-Specific T Cells

Effector T cells are central to immune defense against Mycobacterium tuberculosis (Mtb), exerting complex and multifaceted roles that contribute to both protection and immunopathology. CD4⁺ T cells activate macrophages, maintain granulomas, and coordinate broad immune functions through diverse subsets, including cytokine-producing, cytotoxic, and regulatory cells. CD8⁺ T cells target infected cells through cytolytic activity and cytokine secretion, while unconventional T cells provide rapid, innate-like responses, particularly at mucosal sites. Recent advances in single-cell and spatial transcriptomics have revealed heterogeneity, functional plasticity, and spatial compartmentalization among T-cell subsets. Tissue-resident memory T cells in the lung parenchyma have emerged as key predictors of protective immunity. These insights are reshaping our understanding of T-cell-mediated control of Mtb and highlight the limitations of interferon (IFN)-γ-centric vaccine strategies. Future strategies must aim to elicit a broader range of T-cell responses, promote effective tissue localization, enhance polyfunctionality, and overcome regulatory or exhaustion-associated dysfunctions.