A Critical Role for CD8 T Cells in a Nonhuman Primate Model of Tuberculosis

PLoS Pathog. 2009 Apr;5(4):e1000392. doi: 10.1371/journal.ppat.1000392. Epub 2009 Apr 17.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BCG Vaccine / immunology*
  • CD8 Antigens / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Disease Models, Animal
  • Humans
  • Macaca mulatta
  • Mycobacterium tuberculosis / immunology
  • Mycobacterium tuberculosis / physiology
  • Tuberculosis / immunology*
  • Tuberculosis / prevention & control
  • Vaccination / veterinary

Substances

  • BCG Vaccine
  • CD8 Antigens