Exploring γδ T-Cell Responses in Malaria and Tuberculosis: Implications for Immunity, Coinfection, and Disease Management

This systematic review examines the multifaceted roles of γδ T cells in malaria and tuberculosis (TB) with an emphasis on subset-specific dynamics and functional plasticity. In malaria, γδ T cells, particularly Vγ9Vδ2+ cells, are rapidly activated upon infection with Plasmodium falciparum, exerting antiparasitic effects through the production of proinflammatory cytokines, cytotoxicity, and immune modulation. However, chronic or repeated exposure to malaria leads to the functional exhaustion of Vδ2+ cells, which is characterized by reduced cytokine responsiveness and a shift toward regulatory phenotypes. In TB, γδ T cells contribute to pathogen containment through the secretion of interferon-γ and interleukin-17, the activation of macrophages, and the formation of granulomas. Yet, active TB is often associated with reduced peripheral γδ T-cell frequencies, possibly because of tissue migration or exhaustion. Emerging evidence also highlights distinct roles for CD8+ γδ T cells and Vδ1+ subsets in latent infection and local tissue immunity. Understanding the pathogen-specific and context-dependent functions of γδ T-cell subsets is critical for informing the development of targeted immunotherapies and vaccine strategies against malaria and TB.