Low-Density Granulocytes Affect T-SPOT.TB Assay by Inhibiting the Production of Interferon-γ in T Cells via PD-L1/PD-1 Pathway.
Low-Density Granulocytes Affect T-SPOT.TB Assay by Inhibiting the Production of Interferon-γ in T Cells via PD-L1/PD-1 Pathway.
复制标题
低密度粒细胞通过 PD-L1/PD-1 途径抑制 T 细胞中干扰素-γ 的产生，从而影响 T-SPOT.TB 测定
DOI：
10.3389/fmicb.2020.622389
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发表时间：
2020
影响因子：
5.2
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Rao J;Su R;Peng Y;Guo Y;Huang Z;Ye Y;Gao Y;Liu J;Zhang L;Luo Q;Li J
T-SPOT TB（T-SPOT）检测法是一种以检测结核分枝杆菌为基础的检测结核分枝杆菌感染的方法。外周血单核细胞（PBMC）中的结核特异性分泌干扰素-γ的T细胞（ISC）。近年来，在结核病患者的外周血单个核细胞中发现了高频率的低密度粒细胞（LDGs）。这些LDG是否影响T-SPOT的检测尚未研究。本研究旨在探讨LDGs对T-SPOT检测的影响及其相关机制。对LDG频率与T-SPOT结果进行相关性分析。用去除LDG的PBMC和外源添加LDG的PBMC进行T-SPOT。通过检测LDG上负性免疫调节分子的水平来探讨其可能的机制。程序性死亡配体1（PD-L1）对T-SPOT的影响进行了评估，并通过中和抗体的功能阻断进行了确认。LDGs频率低的肺结核患者（n = 22）T-SPOT和ISCs阳性率明显高于LDGs频率高的肺结核患者（n = 39）。去除或添加外源性LDGs可显著提高或降低ISCs和T-SPOT阳性率。γ-干扰素产生T细胞频率与LDG频率呈负相关。PD-L1的表达在LDG上显著升高。用抗PD-L1抗体预处理LDG可显著抵消LDG对T-SPOT的影响。用抗PD-L1抗体处理PBMC产生与去除LDG相当的ISC。LDGs可通过高表达PD-L1抑制T细胞产生IFN-γ，降低T-SPOT试验阳性率。
T-SPOT TB (T-SPOT) assay is widely used for detection of Mycobacterium tuberculosis infection that is based on the detection of M. tuberculosis-specific interferon-γ-secreting T cells (ISCs) in peripheral blood mononuclear cells (PBMCs). Recently, high frequencies of low-density granulocytes (LDGs) were found in the PBMCs of tuberculosis patients. Whether these LDGs affect the detection of T-SPOT has not been investigated. The impact of LDGs on T-SPOT assay and related mechanism were investigated in this study. The correlations between the frequencies of LDGs and the results of T-SPOT were analyzed. T-SPOT with LDG-removed PBMCs and PBMCs with exogenous addition of LDGs were performed. The possible mechanism was explored by detecting the levels of negative immune regulatory molecules on LDGs. The impact of programmed death ligand 1 (PD-L1) on T-SPOT was evaluated and confirmed by function blocking with neutralizing antibody. The positive rates of T-SPOT and ISCs in tuberculosis patients with low LDGs frequency (n = 22) were significantly higher than those with high LDGs frequency (n = 39). Removal or exogenous addition of LDGs significantly increased or decreased the ISCs and the positive rate of T-SPOT. The frequencies of interferon-γ-producing T cells were negatively correlated with the frequencies of LDGs. The expression of PD-L1 was significantly elevated on LDGs. Pretreatment of LDGs with anti-PD-L1 antibody significantly counteracted the impact of LDGs on T-SPOT. Treatment of PBMCs with anti-PD-L1 antibody resulted in comparable ISCs with that of LDG removal. LDGs can inhibit the production of interferon-γ in T cells and decrease the positive rated of T-SPOT assay via highly expressed PD-L1.
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