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Type: Journal article
Title: A critical role for CD8 T cells in a nonhuman primate model of tuberculosis
Author: Chen, C.
Huang, D.
Wang, R.
Shen, L.
Zeng, G.
Yao, S.
Shen, Y.
Halliday, L.
Fortman, J.
McAllister, M.
Estep, J.
Hunt, R.
Vasconcelos, D.
Du, G.
Porcelli, S.
Larsen, M.
Jacobs Jr, W.
Haynes, B.
Letvin, N.
Chen, Z.
Citation: PLoS Pathogens, 2009; 5(4):1-11
Publisher: Public Library of Science
Issue Date: 2009
ISSN: 1553-7366
Statement of
Crystal Y. Chen, Dan Huang, Richard C. Wang, Ling Shen, Gucheng Zeng, Shuyun Yao, Yun Shen, Lisa Halliday, Jeff Fortman, Milton McAllister, Jim Estep, Robert Hunt, Daphne Vasconcelos, George Du, Steven A. Porcelli, Michelle H. Larsen, William R. Jacobs, Jr., Barton F. Haynes, Norman L. Letvin and Zheng W. Chen
Abstract: The role of CD8 T cells in anti-tuberculosis immunity in humans remains unknown, and studies of CD8 T cell–mediated protection against tuberculosis in mice have yielded controversial results. Unlike mice, humans and nonhuman primates share a number of important features of the immune system that relate directly to the specificity and functions of CD8 T cells, such as the expression of group 1 CD1 proteins that are capable of presenting Mycobacterium tuberculosis lipids antigens and the cytotoxic/bactericidal protein granulysin. Employing a more relevant nonhuman primate model of human tuberculosis, we examined the contribution of BCG- or M. tuberculosis-elicited CD8 T cells to vaccine-induced immunity against tuberculosis. CD8 depletion compromised BCG vaccine-induced immune control of M. tuberculosis replication in the vaccinated rhesus macaques. Depletion of CD8 T cells in BCG-vaccinated rhesus macaques led to a significant decrease in the vaccine-induced immunity against tuberculosis. Consistently, depletion of CD8 T cells in rhesus macaques that had been previously infected with M. tuberculosis and cured by antibiotic therapy also resulted in a loss of anti-tuberculosis immunity upon M. tuberculosis re-infection. The current study demonstrates a major role for CD8 T cells in anti-tuberculosis immunity, and supports the view that CD8 T cells should be included in strategies for development of new tuberculosis vaccines and immunotherapeutics.
Keywords: CD8-Positive T-Lymphocytes; Animals; Macaca mulatta; Humans; Mycobacterium tuberculosis; Tuberculosis; Disease Models, Animal; Antigens, CD8; BCG Vaccine; Vaccination
Rights: © 2009 Chen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
RMID: 0020098219
DOI: 10.1371/journal.ppat.1000392
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