Immune distribution and localization of phosphoantigen-specific V gamma 2V delta 2 T cells in lymphoid and nonlymphoid tissues in Mycobacterium tuberculosis infection

Little is known about the immune distribution and localization of antigen-specific T cells in mucosal interfaces of tissues/organs during infection of humans. In this study, we made use of a macaque model of Mycobacterium tuberculosis infection to assess phosphoantigen-specific V gamma 2V delta 2 T cells regarding their tissue distribution, anatomical localization, and correlation with the presence or absence of tuberculosis (TB) lesions in lymphoid and nonlymphoid organs/tissues in the progression of severe pulmonary TB. Progression of pulmonary M. tuberculosis infection generated diverse distribution patterns of V gamma 2V delta 2 T cells, with remarkable accumulation of these cells in lungs, bronchial lymph nodes, spleens, and remote nonlymphoid organs but not in blood. Increased numbers of V gamma 2V delta 2 T cells in tissues were associated with M. tuberculosis infection but were independent of the severity of TB lesions. In lungs with apparent TB lesions, V gamma 2V delta 2 T cells were present within TB granulomas. In extrathoracic organs, V gamma 2V delta 2 T cells were localized in the interstitial compartment of nonlymphoid tissues, and the interstitial localization was present despite the absence of detectable TB lesions. Finally, V gamma 2V delta 2 T cells accumulated in tissues appeared to possess cytokine production function, since granzyme B was detectable in the gamma delta T cells present within granulomas. Thus, clonally expanded V gamma 2V delta 2 T cells appeared to undergo trans-endothelial migration, interstitial localization, and granuloma infiltration as immune responses to M. tuberculosis infection.