Abstract
The functional role of ILT2 in anti-tuberculosis immunity remains to be elucidated. In this study, we investigated expression and functions of ILT2 on NK cells during TB infection. The frequency of CD56(dim)CD16(+) NK cells that expressed ILT2 was significantly elevated in patients with active pulmonary TB as compared with tuberculin-positive healthy controls (p < 0.0001). TB patients with Mycobacterium tuberculosis smear/culture-positive result had significantly higher frequency of ILT2-expressing CD56(dim)CD16(+) NK cells than those with M. tuberculosis smear/culture-negative result (p < 0.0001), suggesting that ILT2 expression on CD56(dim)CD16(+) NK cells correlated with disease severity of pulmonary TB. ILT2-expressing CD56(dim) NK cells had a functional defect, as evidenced by reduced expression of CD107a and IFN-γ. Spontaneous apoptosis in ILT2(+)CD56(dim) NK cells was higher than in ILT2(-) cells. Blocking of ILT2 signaling resulted in increased expression of CD107a on CD56(dim)CD16(+) NK cells. It is concluded that ILT2 has an inhibitory role on NK cells in patients with active TB.
Keywords:
ILT2; Immunity; NK cells; Tuberculosis.
Copyright © 2014 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Antigens, CD / immunology
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Antigens, CD / metabolism*
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Apoptosis
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Biomarkers / metabolism
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CD56 Antigen / immunology
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CD56 Antigen / metabolism*
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Case-Control Studies
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Coculture Techniques
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Female
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GPI-Linked Proteins / immunology
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GPI-Linked Proteins / metabolism
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Humans
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Immunophenotyping
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Interferon-gamma / metabolism
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K562 Cells
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism*
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Killer Cells, Natural / microbiology
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Killer Cells, Natural / pathology
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Leukocyte Immunoglobulin-like Receptor B1
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Lysosomal-Associated Membrane Protein 1 / metabolism
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Male
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Middle Aged
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Mycobacterium tuberculosis / immunology
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Mycobacterium tuberculosis / pathogenicity*
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Predictive Value of Tests
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Receptors, IgG / immunology*
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Receptors, IgG / metabolism*
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Receptors, Immunologic / immunology
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Receptors, Immunologic / metabolism*
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Severity of Illness Index
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Signal Transduction
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Sputum / cytology
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Sputum / immunology
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Sputum / microbiology
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Tuberculosis, Pulmonary / diagnosis
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Tuberculosis, Pulmonary / immunology
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Tuberculosis, Pulmonary / metabolism*
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Young Adult
Substances
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Antigens, CD
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Biomarkers
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CD56 Antigen
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FCGR3B protein, human
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GPI-Linked Proteins
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IFNG protein, human
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LILRB1 protein, human
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Leukocyte Immunoglobulin-like Receptor B1
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Lysosomal-Associated Membrane Protein 1
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NCAM1 protein, human
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Receptors, IgG
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Receptors, Immunologic
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Interferon-gamma