A critical role for CD8 T cells in a nonhuman primate model of tuberculosis.

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, Barton F Haynes, Norman L Letvin, Zheng W Chen

Index: PLoS Pathog. 5 , e1000392, (2009)

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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.