Increased frequency of ILT2-expressing CD56^dimCD16⁺ NK cells correlates with disease severity of pulmonary tuberculosis - 19/09/14

Doi : 10.1016/j.tube.2014.03.009

Xinjing Wang ^a,^{^{1
Both authors contributed equally to the work.}}, Xianghong Meng ^a,^b,^{^{1
Both authors contributed equally to the work.}}, Yue Zheng ^a, Jing Jiang ^a, Bingfen Yang ^a, Yanhua Liu ^a, Fei Zhai ^a, Xiaoxing Cheng ^a,^⁎
^a Key Laboratory of Tuberculosis Prevention and Treatment of PLA, Division of Research, Institute of Tuberculosis, 309 Hospital, Beijing, China
^b Chinese Academy of Military Medical Sciences, Beijing, China

^∗Corresponding author. Division of Research, Institute of Tuberculosis, 309 Hospital, 17 Hei Shan Hu Road, Haidian, Beijing 100091, China. Tel./fax: +86 10 51520496.

Summary

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^dimCD16⁺ 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^dimCD16⁺ NK cells than those with M. tuberculosis smear/culture-negative result (p < 0.0001), suggesting that ILT2 expression on CD56^dimCD16⁺ 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^dimCD16⁺ NK cells. It is concluded that ILT2 has an inhibitory role on NK cells in patients with active TB.

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Keywords : Tuberculosis, Immunity, ILT2, NK cells

Plan

Introduction

Materials and methods

Human subjects

Preparation of human PBMCs

Phenotypic analysis of NK cells

Analysis of spontaneous apoptosis of NK cells

NK cell degranulation assay

Intracellular staining of IFN-γ

Statistical analysis

Results

Patients with active TB had increased proportion of ILT2-expressing CD16⁺CD56^dim NK cells

Frequency of ILT2-expressing CD56^dimCD16⁺ NK cells correlated with disease severity of pulmonary TB

ILT2-expressing CD56^dim NK cells had functional defect

Spontaneous apoptosis rate of ILT2⁺CD56^dim NK cells was higher than ILT2⁻ cells

Blocking ILT2 signaling resulted in increased expression of CD107a on CD56^dimCD16⁺ NK cells

Discussion

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Vol 94 - N° 5

P. 469-474 - septembre 2014 Retour au numéro

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Increased frequency of ILT2-expressing CD56^dimCD16⁺ NK cells correlates with disease severity of pulmonary tuberculosis - 19/09/14

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