Immune Distribution and Localization of Phosphoantigen-Specific V gamma 2V delta 2 T Cells in Lymphoid and Nonlymphoid Tissues in Mycobacterium tuberculosis Infection

• Published in: Infection and immunity 2008-01, Vol.76 (1), p.426-436
• Main Authors: Huang, Dan, Shen, Yun, Qiu, Liyou, Chen, Crystal Y, Shen, Ling, Estep, Jim, Hunt, Robert, Vasconcelos, Daphne, Du, George, Aye, Pyone, Lackner, Andrew A, Larsen, Michelle H, Jacobs, William RJr, Haynes, Barton F, Letvin, Norman L, Chen, Zheng W
• Format: Article
• Language: English
• Subjects: Macaca; Mycobacterium tuberculosis
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.01008-07

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.