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.