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

Overview

Journal PLoS Pathog

Specialty Microbiology

Date 2009 Apr 22

PMID 19381260

Citations 163

Authors

Crystal Y Chen

Dan Huang

Richard C Wang

Ling Shen

Gucheng Zeng

Shuyun Yao

Yun Shen

Lisa Halliday

Jeff Fortman

Milton McAllister

Jim Estep

Robert Hunt

Daphne Vasconcelos

George Du

Steven A Porcelli

Michelle H Larsen

William R Jacobs Jr

Barton F Haynes

Norman L Letvin

Zheng W Chen

Affiliations

Soon will be listed here.

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.

Citing Articles

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References

Boom W, Canaday D, Fulton S, Gehring A, Rojas R, Torres M . Human immunity to M. tuberculosis: T cell subsets and antigen processing. Tuberculosis (Edinb). 2003; 83(1-3):98-106. DOI: 10.1016/s1472-9792(02)00054-9. View

Shen Y, Shen L, Sehgal P, Huang D, Qiu L, Du G . Clinical latency and reactivation of AIDS-related mycobacterial infections. J Virol. 2004; 78(24):14023-32. PMC: 533912. DOI: 10.1128/JVI.78.24.14023-14032.2004. View

Reimann K, Parker R, Seaman M, Beaudry K, Beddall M, Peterson L . Pathogenicity of simian-human immunodeficiency virus SHIV-89.6P and SIVmac is attenuated in cynomolgus macaques and associated with early T-lymphocyte responses. J Virol. 2005; 79(14):8878-85. PMC: 1168747. DOI: 10.1128/JVI.79.14.8878-8885.2005. View

Soysal A, Millington K, Bakir M, Dosanjh D, Aslan Y, Deeks J . Effect of BCG vaccination on risk of Mycobacterium tuberculosis infection in children with household tuberculosis contact: a prospective community-based study. Lancet. 2005; 366(9495):1443-51. DOI: 10.1016/S0140-6736(05)67534-4. View

Rosat J, Grant E, Beckman E, Dascher C, Sieling P, Frederique D . CD1-restricted microbial lipid antigen-specific recognition found in the CD8+ alpha beta T cell pool. J Immunol. 1999; 162(1):366-71. View

Mogues T, Goodrich M, Ryan L, LaCourse R, NORTH R . The relative importance of T cell subsets in immunity and immunopathology of airborne Mycobacterium tuberculosis infection in mice. J Exp Med. 2001; 193(3):271-80. PMC: 2195922. DOI: 10.1084/jem.193.3.271. View

Wells C, Cegielski J, Nelson L, Laserson K, Holtz T, Finlay A . HIV infection and multidrug-resistant tuberculosis: the perfect storm. J Infect Dis. 2007; 196 Suppl 1:S86-107. DOI: 10.1086/518665. View

Shen Y, Zhou D, Qiu L, Lai X, Simon M, Shen L . Adaptive immune response of Vgamma2Vdelta2+ T cells during mycobacterial infections. Science. 2002; 295(5563):2255-8. PMC: 2872146. DOI: 10.1126/science.1068819. View

Muller I, Cobbold S, Waldmann H, Kaufmann S . Impaired resistance to Mycobacterium tuberculosis infection after selective in vivo depletion of L3T4+ and Lyt-2+ T cells. Infect Immun. 1987; 55(9):2037-41. PMC: 260652. DOI: 10.1128/iai.55.9.2037-2041.1987. View

10.

Wu Y, Woodworth J, Shin D, Morris S, Behar S . Vaccine-elicited 10-kilodalton culture filtrate protein-specific CD8+ T cells are sufficient to mediate protection against Mycobacterium tuberculosis infection. Infect Immun. 2008; 76(5):2249-55. PMC: 2346695. DOI: 10.1128/IAI.00024-08. View

11.

Teleshova N, Kenney J, Jones J, Marshall J, Van Nest G, Dufour J . CpG-C immunostimulatory oligodeoxyribonucleotide activation of plasmacytoid dendritic cells in rhesus macaques to augment the activation of IFN-gamma-secreting simian immunodeficiency virus-specific T cells. J Immunol. 2004; 173(3):1647-57. DOI: 10.4049/jimmunol.173.3.1647. View

12.

Sousa A, Mazzaccaro R, Russell R, Lee F, Turner O, Hong S . Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice. Proc Natl Acad Sci U S A. 2000; 97(8):4204-8. PMC: 18197. DOI: 10.1073/pnas.97.8.4204. View

13.

Barclay W, Busey W, Dalgard D, Good R, JANICKI B, Kasik J . Protection of monkeys against airborne tuberculosis by aerosol vaccination with bacillus Calmette-Guerin. Am Rev Respir Dis. 1973; 107(3):351-8. DOI: 10.1164/arrd.1973.107.3.351. View

14.

Shen Y, Shen L, Sehgal P, Zhou D, Simon M, Miller M . Antiretroviral agents restore Mycobacterium-specific T-cell immune responses and facilitate controlling a fatal tuberculosis-like disease in Macaques coinfected with simian immunodeficiency virus and Mycobacterium bovis BCG. J Virol. 2001; 75(18):8690-6. PMC: 115114. DOI: 10.1128/jvi.75.18.8690-8696.2001. View

15.

Stenger S, Mazzaccaro R, Uyemura K, Cho S, Barnes P, Rosat J . Differential effects of cytolytic T cell subsets on intracellular infection. Science. 1997; 276(5319):1684-7. DOI: 10.1126/science.276.5319.1684. View

16.

Rodrigues L, Diwan V, Wheeler J . Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. Int J Epidemiol. 1993; 22(6):1154-8. DOI: 10.1093/ije/22.6.1154. View

17.

Schaible U, Collins H, Priem F, Kaufmann S . Correction of the iron overload defect in beta-2-microglobulin knockout mice by lactoferrin abolishes their increased susceptibility to tuberculosis. J Exp Med. 2002; 196(11):1507-13. PMC: 2194267. DOI: 10.1084/jem.20020897. View

18.

Dsouza C, Cooper A, Frank A, Ehlers S, Turner J, Bendelac A . A novel nonclassic beta2-microglobulin-restricted mechanism influencing early lymphocyte accumulation and subsequent resistance to tuberculosis in the lung. Am J Respir Cell Mol Biol. 2000; 23(2):188-93. DOI: 10.1165/ajrcmb.23.2.4063. View

19.

Leveton C, Barnass S, Champion B, Lucas S, de Souza B, Nicol M . T-cell-mediated protection of mice against virulent Mycobacterium tuberculosis. Infect Immun. 1989; 57(2):390-5. PMC: 313109. DOI: 10.1128/iai.57.2.390-395.1989. View

20.

Qiu L, Huang D, Chen C, Wang R, Shen L, Shen Y . Severe tuberculosis induces unbalanced up-regulation of gene networks and overexpression of IL-22, MIP-1alpha, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-beta, TIM1, and TLR2 but low antigen-specific cellular responses. J Infect Dis. 2008; 198(10):1514-9. PMC: 2884371. DOI: 10.1086/592448. View