A critical role for CD8 T cells in a nonhuman primate model of tuberculosis.
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.
Chen
Crystal Y
CY
Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, Illinois, USA.
Huang
Dan
D
Wang
Richard C
RC
Shen
Ling
L
Zeng
Gucheng
G
Yao
Shuyun
S
Shen
Yun
Y
Halliday
Lisa
L
Fortman
Jeff
J
McAllister
Milton
M
Estep
Jim
J
Hunt
Robert
R
Vasconcelos
Daphne
D
Du
George
G
Porcelli
Steven A
SA
Larsen
Michelle H
MH
Jacobs
William R
WR
Haynes
Barton F
BF
Letvin
Norman L
NL
Chen
Zheng W
ZW
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
D001500:BCG Vaccine; D016827:CD8 Antigens