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

Research output: Contribution to journalArticle

162 Scopus citations

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.

Original languageEnglish (US)
JournalPLoS pathogens
Volume5
Issue number4
DOIs
StatePublished - Apr 2009

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Chen, C. Y., Huang, D., Wang, R. C., Shen, L., Zeng, G., Yao, S., Shen, Y., Halliday, L., Fortman, J., McAllister, M., Estep, J., Hunt, R., Vasconcelos, D., Du, G., Porcelli, S. A., Larsen, M. H., Jacobs, W. R., Haynes, B. F., Letvin, N. L., & Chen, Z. W. (2009). A critical role for CD8 T cells in a nonhuman primate model of tuberculosis. PLoS pathogens, 5(4). https://doi.org/10.1371/journal.ppat.1000392