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

PLoS Pathogens

Lisa Halliday¹  Jeff Fortman¹  Daphne Vasconcelos²  Robert Hunt²  Jim Estep²  Steven A. Porcelli³  Michelle H. Larsen³  Barton F. Haynes³  Shuyun Yao⁴  Gucheng Zeng⁴  Dan Huang⁴  Yun Shen⁴  Richard C. Wang⁴  George Du⁴  Crystal Y. Chen⁴  Milton McAllister⁵  Zheng W. Chen⁶  Ling Shen⁷  William R. Jacobs Jr.⁸  Norman L. Letvin⁸ 

[1] BRL, University of Illinois, Chicago, Illinois, United States of America;Battelle Medical Research Evaluation Facility, Battelle Memorial Institute, Columbus, Ohio, United States of America;Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York, United States of America;Department of Microbiology and Immunology, Center for Primate Biomedical Research, University of Illinois College of Medicine, Chicago, Illinois, United States of America;Department of Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana-Champaign, Illinois, United States of America;Duke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America;Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America;Howard Hughes Medical Institute and Albert Einstein College of Medicine, Bronx, New York, United States of America

关键词: Macaque;    Cytotoxic T cells;    Mycobacterium tuberculosis;    T cells;    Tuberculosis;    Granulomas;    Antibody isotypes;    Cell-mediated immunity;   

DOI  :  10.1371/journal.ppat.1000392

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY