Mucosal-associated Invariant T-Cell Function Is Modulated by Programmed Death-1 Signaling in Patients with Active Tuberculosis.

RATIONALE: Mucosal-associated invariant T (MAIT) cells have been proven to play an important role in host defense against mycobacterial infection in animal infection models; however, the functional role of MAIT cells in patients with active tuberculosis (TB) is still largely unknown. OBJECTIVES: To...

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Published in:American Journal of Respiratory & Critical Care Medicine Vol. 190; no. 3; pp. 329 - 340
Main Authors: Jiang, Jing, Wang, Xinjing, An, Hongjuan, Yang, Bingfen, Cao, Zhihong, Liu, Yanhua, Su, Jinwen, Zhai, Fei, Wang, Ruo, Zhang, Guangyu, Cheng, Xiaoxing
Format: research Journal Article
Published: Oxford University Press / USA 8/1/2014
Online Access:View this record in EBSCOhost
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      dt: 8/1/2014
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      pub: Oxford University Press / USA
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        10.1164/rccm.201401-0106OC
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        103979353
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        atl: Mucosal-associated Invariant T-Cell Function Is Modulated by Programmed Death-1 Signaling in Patients with Active Tuberculosis.
      aug:
        au:
          Jiang, Jing
          Wang, Xinjing
          An, Hongjuan
          Yang, Bingfen
          Cao, Zhihong
          Liu, Yanhua
          Su, Jinwen
          Zhai, Fei
          Wang, Ruo
          Zhang, Guangyu
          Cheng, Xiaoxing
        affil: Key Laboratory of Tuberculosis Prevention and Treatment, Division of Research, Institute of Tuberculosis, 309th Hospital, Beijing, China.
      sug:
        subj:
          Apoptosis Immunology
          T Lymphocytes Immunology
          Tuberculosis Immunology
          Adult
          Case Control Studies
          Female
          Flow Cytometry
          Human
          Immunity
          Male
          Peritonitis Immunology
          Nonparametric Statistics
          Tuberculosis, Pulmonary Immunology
          Adult: 19-44 years
          Female
          Male
      ab: RATIONALE: Mucosal-associated invariant T (MAIT) cells have been proven to play an important role in host defense against mycobacterial infection in animal infection models; however, the functional role of MAIT cells in patients with active tuberculosis (TB) is still largely unknown. OBJECTIVES: To understand the clinical features and functions of MAIT cells in patients with active TB. METHODS: MAIT cells were analyzed in patients with pulmonary TB, tuberculous pleurisy, and tuberculous peritonitis by flow cytometry. The functions of MAIT cells were compared between patients with active TB and healthy control subjects. MEASUREMENTS AND MAIN RESULTS: The frequency of MAIT cells was significantly reduced both in peripheral blood from patients with active pulmonary TB (P < 0.0001) and in tuberculous pleural effusions compared with healthy control subjects but not in ascitic fluids from patients with tuberculous peritonitis. A comparison of bacillus Calmette-Guérin (BCG)-stimulated cytokine production showed that patients with active TB had significantly higher production of IFN-[gamma] (P = 0.0034) and tumor necrosis factor (TNF)-[alpha] (P = 0.0399) compared with healthy control subjects. In contrast, when MAIT cells were stimulated with Escherichia coli, patients with active TB had significantly lower production of IFN-[gamma] (P = 0.0007) and TNF-[alpha] (P = 0.0032). MAIT cells in patients with active TB exhibited elevated expression of programmed death-1 (PD-1) (P = 0.0015), and blockade of PD-1 signaling resulted in a significantly higher frequency of BCG-stimulated IFN-[gamma] production in MAIT cells (P = 0.0178). CONCLUSIONS: MAIT-cell immune response to antigen stimulation in patients with active TB is regulated by PD-1, which could be a potential target for TB immunotherapy.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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