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.
Highlights
Tuberculosis remains one of the major causes of global mortality, and has become increasingly prevalent and deadly as a result of HIV/AIDS pandemic and the emergence of extensively drug resistant (XDR) strains of M. tuberculosis [1]
While CD4 T cells are well described for their protection against tuberculosis, little is known about the role of human CD8 T cells in antituberculosis immunity
We found that CD8 T cells play a role in Bacille Calmette-Guerin (BCG) vaccine-induced immune control of Mycobacterium tuberculosis replication and in the vaccine-induced immunity against tuberculosis
Summary
Tuberculosis remains one of the major causes of global mortality, and has become increasingly prevalent and deadly as a result of HIV/AIDS pandemic and the emergence of extensively drug resistant (XDR) strains of M. tuberculosis [1]. It is widely accepted that CD4 T cells play a critical role in the ability of humans and experimental animals to resist active M. tuberculosis infection [7], the contribution of CD8 T cells to natural or BCG-induced immunity against tuberculosis remains unclear. We propose that nonhuman primates should provide more relevant models for evaluating a role of human CD8+ T cells in BCG vaccine-induced immunity against tuberculosis [6,26,27,28,29,30]. Unlike mice and other rodents studied to date, rhesus macaques share with humans a number of important features of the immune system that relate directly to the specificity and functions of CD8 T
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