Immune distribution and localization of phosphoantigen-specific Vgamma2Vdelta2 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 Vgamma2Vdelta2 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 Vgamma2Vdelta2 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 Vgamma2Vdelta2 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, Vgamma2Vdelta2 T cells were present within TB granulomas. In extrathoracic organs, Vgamma2Vdelta2 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, Vgamma2Vdelta2 T cells accumulated in tissues appeared to possess cytokine production function, since granzyme B was detectable in the gammadelta T cells present within granulomas. Thus, clonally expanded Vgamma2Vdelta2 T cells appeared to undergo trans-endothelial migration, interstitial localization, and granuloma infiltration as immune responses to M. tuberculosis infection.
Huang, D; Shen, Y; Qiu, L; Chen, CY; Shen, L; Estep, J; Hunt, R; Vasconcelos, D; Du, G; Aye, P; Lackner, AA; Larsen, MH; Jacobs, WR; Haynes, BF; Letvin, NL; Chen, ZW
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