Immune distribution and localization of phosphoantigen-specific Vγ2Vδ2 T cells in lymphoid and nonlymphoid tissues in Mycobacterium tuberculosis infection

Dan Huang, Yun Shen, Liyou Qiu, Crystal Y. Chen, Ling Shen, Jim Estep, Robert Hunt, Daphne Vasconcelos, George Du, Pyone Aye, Andrew A. Lackner, Michelle H. Larsen, William R. Jacobs, Barton F. Haynes, Norman L. Letvin, Zheng W. Chen

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

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 Vγ2Vδ2 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 Vγ2Vδ2 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 Vγ2Vδ2 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, Vγ2Vδ2 T cells were present within TB granulomas. In extrathoracic organs, Vγ2Vδ2 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, Vγ2Vδ2 T cells accumulated in tissues appeared to possess cytokine production function, since granzyme B was detectable in the γδ T cells present within granulomas. Thus, clonally expanded Vγ2Vδ2 T cells appeared to undergo trans-endothelial migration, interstitial localization, and granuloma infiltration as immune responses to M. tuberculosis infection.

Original languageEnglish (US)
Pages (from-to)426-436
Number of pages11
JournalInfection and immunity
Volume76
Issue number1
DOIs
StatePublished - Jan 2008

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

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