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
Dan
D
Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine at Chicago, 909 S. Wolcott Ave., Chicago, IL 60612, USA.
Shen
Yun
Y
Qiu
Liyou
L
Chen
Crystal Y
CY
Shen
Ling
L
Estep
Jim
J
Hunt
Robert
R
Vasconcelos
Daphne
D
Du
George
G
Aye
Pyone
P
Lackner
Andrew A
AA
Larsen
Michelle H
MH
Jacobs
William R
WR
Haynes
Barton F
BF
Letvin
Norman L
NL
Chen
Zheng W
ZW
D000818:Animals; D000942:Antigens, Bacterial; D006099:Granuloma; D007371:Interferon-gamma / Q000378:metabolism; D008168:Lung / Q000473:pathology; D008221:Lymphoid Tissue / Q000166:cytology*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D009169:Mycobacterium tuberculosis; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology
D000942:Antigens, Bacterial; D007371:Interferon-gamma