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

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)132-139
Number of pages8
JournalInfection and Immunity
Volume82
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

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T Lymphocyte Differentiation Antigens
Mycobacterium Infections
Mycobacterium tuberculosis
T-Lymphocytes
Tumor Necrosis Factor-alpha
Infection
Lymphocytic choriomeningitis virus
Virus Diseases
Interferon-alpha
Interferon-gamma
Interleukin-2

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

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title = "Differentiation of antigen-specific T cells with limited functional capacity during Mycobacterium tuberculosis infection",
abstract = "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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Differentiation of antigen-specific T cells with limited functional capacity during Mycobacterium tuberculosis infection. / Jeong, Yun Hee; Jeon, Bo Young; Gu, Sun Hwa; Cho, Sang Nae; Shin, Sung Jae; Chang, Jun; Ha, Sang Jun.

In: Infection and Immunity, Vol. 82, No. 1, 01.01.2014, p. 132-139.

Research output: Contribution to journalArticle

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AU - Jeong, Yun Hee

AU - Jeon, Bo Young

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AU - Shin, Sung Jae

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AB - 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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