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Infection and Immunity, January 2008, p. 426-436, Vol. 76, No. 1
0019-9567/08/$08.00+0     doi:10.1128/IAI.01008-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Immune Distribution and Localization of Phosphoantigen-Specific V2V2 T Cells in Lymphoid and Nonlymphoid Tissues in Mycobacterium tuberculosis Infection

Dan Huang,^1, Yun Shen,^1, Liyou Qiu,¹ Crystal Y. Chen,¹ Ling Shen,² Jim Estep,³ Robert Hunt,³ Daphne Vasconcelos,³ George Du,¹ Pyone Aye,⁴ Andrew A. Lackner,⁴ Michelle H. Larsen,⁵ William R. Jacobs Jr.,⁵ Barton F. Haynes,⁶ Norman L. Letvin,² and Zheng W. Chen^1*

Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine at Chicago, Chicago, Illinois,¹ Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts,² Battelle Medical Research/Evaluation Facility, Battelle Memorial Institute, Columbus, Ohio,³ Tulane National Primate Research Center, Covington, Louisiana,⁴ Howard Hughes Medical Institute and Albert Einstein College of Medicine, New York, New York,⁵ Duke Human Vaccine Institute, Duke University, Durham, North Carolina⁶

Received 23 July 2007/ Returned for modification 1 September 2007/ Accepted 29 September 2007

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 V2V2 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 V2V2 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 V2V2 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, V2V2 T cells were present within TB granulomas. In extrathoracic organs, V2V2 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, V2V2 T cells accumulated in tissues appeared to possess cytokine production function, since granzyme B was detectable in the T cells present within granulomas. Thus, clonally expanded V2V2 T cells appeared to undergo trans-endothelial migration, interstitial localization, and granuloma infiltration as immune responses to M. tuberculosis infection.

Published ahead of print on 8 October 2007.

Editor: A. J. Bäumler

The first two authors contributed equally to this work.

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