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Differentiation of Antigen-Specific T Cells with Limited Functional Capacity during Mycobacterium tuberculosis Infection

 Yun Hee Jeong  ;  Bo-Young Jeon  ;  Sun-Hwa Gu  ;  Sang-Nae Cho  ;  Sung Jae Shin  ;  Jun Chang  ;  Sang-Jun Ha 
 INFECTION AND IMMUNITY, Vol.82(1) : 132-139, 2014 
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Animals ; Antigens, Bacterial/immunology ; Antigens, Differentiation/immunology ; Bacterial Load ; CD4-Positive T-Lymphocytes/immunology* ; CD8-Positive T-Lymphocytes/immunology* ; Cell Differentiation/immunology ; Chronic Disease ; Disease Models, Animal ; Female ; Immunity, Cellular/immunology ; Immunologic Memory/physiology ; Interferon-gamma/metabolism ; Longitudinal Studies ; Mice ; Mice, Inbred C57BL ; Mycobacterium tuberculosis/immunology* ; Phenotype ; T-Lymphocytes, Helper-Inducer/immunology ; Tuberculosis/immunology* ; Tumor Necrosis Factor-alpha/metabolism
Despite the generation of Mycobacterium tuberculosis-specific T cell immune responses during the course of infection, only 5 to 10% of exposed individuals develop active disease, while others develop a latent infection. This phenomenon suggests defective M. tuberculosis-specific immunity, which necessitates more careful characterization of M. tuberculosis-specific T cell responses. Here, we longitudinally analyzed the phenotypes and functions of M. tuberculosis-specific T cells. In contrast to the functional exhaustion of T cells observed after chronic infection, M. tuberculosis-specific CD8+ T cells differentiated into either effector (CD127lo CD62Llo) or effector memory (CD127hi CD62Llo) cells, but not central memory cells (CD127hi CD62Lhi), with low programmed death 1 (PD-1) expression, even in the presence of high levels of bacteria. Additionally, M. tuberculosis-specific CD8+ and CD4+ T cells produced substantial levels of tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ), but not interleukin 2 (IL-2), upon in vitro restimulation. Among M. tuberculosis-specific CD8+ T cells, CD127hi effector memory cells displayed slower ongoing turnover but greater survival potential. In addition, these cells produced more IFN-γ and TNF-α and displayed lytic activity upon antigen stimulation. However, the effector function of M. tuberculosis-specific CD8+ CD127hi effector memory T cells was inferior to that of canonical CD8+ CD127hi memory T cells generated after acute lymphocytic choriomeningitis virus infection. Collectively, our data demonstrate that M. tuberculosis-specific T cells can differentiate into memory T cells during the course of M. tuberculosis infection independent of the bacterial burden but with limited functionality. These results provide a framework for further understanding the mechanisms of M. tuberculosis infection that can be used to develop more effective vaccines.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Gu, Sun Hwa(구선화)
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
Cho, Sang Nae(조상래)
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