title: A critical role for CD8 T cells in a nonhuman primate model of tuberculosis.
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.
authors.affiliation: Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, Illinois, USA.
authors.forename: Crystal Y
authors.initials: CY
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Richard C
authors.initials: RC
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.forename: Gucheng
authors.initials: G
authors.lastname: Zeng
authors.forename: Shuyun
authors.initials: S
authors.lastname: Yao
authors.forename: Yun
authors.initials: Y
authors.lastname: Shen
authors.forename: Lisa
authors.initials: L
authors.lastname: Halliday
authors.forename: Jeff
authors.initials: J
authors.lastname: Fortman
authors.forename: Milton
authors.initials: M
authors.lastname: McAllister
authors.forename: Jim
authors.initials: J
authors.lastname: Estep
authors.forename: Robert
authors.initials: R
authors.lastname: Hunt
authors.forename: Daphne
authors.initials: D
authors.lastname: Vasconcelos
authors.forename: George
authors.initials: G
authors.lastname: Du
authors.forename: Steven A
authors.initials: SA
authors.lastname: Porcelli
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Larsen
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D006801:Humans; D008253:Macaca mulatta; D009169:Mycobacterium tuberculosis / Q000276:immunology / Q000502:physiology; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control; D014611:Vaccination / Q000662:veterinary
chemical_list: D001500:BCG Vaccine; D016827:CD8 Antigens