结核患者黏膜相关恒定 T 细胞表现出免疫应答受损。
Mucosal-associated invariant T cells from patients with tuberculosis exhibit impaired immune response.
机构信息
Key Laboratory of Tuberculosis Prevention and Treatment, and Beijing Key Laboratory of New Techniques for Tuberculosis Diagnosis and Treatment, Division of Research, Institute of Tuberculosis, 309th Hospital, Beijing, China.
Key Laboratory of Tuberculosis Prevention and Treatment, and Beijing Key Laboratory of New Techniques for Tuberculosis Diagnosis and Treatment, Division of Research, Institute of Tuberculosis, 309th Hospital, Beijing, China.
出版信息
J Infect. 2016 Mar;72(3):338-52. doi: 10.1016/j.jinf.2015.11.010. Epub 2015 Dec 24.
OBJECTIVES
To identify factors which regulate MAIT cell response to Mycobacterium tuberculosis antigens, and to investigate the role of MAIT cells in patients with active tuberculosis.
METHODS
Immune response of MAIT cells to M. tuberculosis antigens were compared between patients with active TB and healthy controls by flow cytometry and RNA sequencing.
RESULTS
IFN-γ response of MAIT cells to M. tuberculosis lysates was dramatically improved by signal 3 cytokine IL-15 (p = 0.0002). Patients with active TB exhibited highly reduced IFN-γ production in MAIT cells stimulated with M. tuberculosis lysates/IL-15 compared with healthy controls (p < 0.0001) and individuals with latent TB infection (p = 0.0008). RNA sequencing of flow-sorted MAIT cells from patients with TB and healthy controls identified numerous differentially expressed genes, and the expression of genes that encode IFN-γ, TNF-α, IL-17F, granulysin and granzyme B were all down-regulated in patients with TB. MAIT cells from patients with TB has significantly lower expression of γc receptor than those from healthy controls under condition of Mtb lysates/IL-15 stimulation (p = 0.0028). Blockade of both γc and IL-2Rβ receptors resulted in highly reduced frequency of IFN-γ-producing MAIT cells (79.4%) (p = 0.0011).
CONCLUSIONS
MAIT cells from patients with active TB exhibited impaired cytokine and cytotoxic response to M. tuberculosis antigens.
目的
确定调节 MAIT 细胞对结核分枝杆菌抗原反应的因素，并研究 MAIT 细胞在活动性肺结核患者中的作用。
方法
通过流式细胞术和 RNA 测序比较活动性结核病患者和健康对照者 MAIT 细胞对结核分枝杆菌抗原的免疫反应。
结果
信号 3 细胞因子 IL-15 显著改善 MAIT 细胞对结核分枝杆菌裂解物的 IFN-γ反应（p = 0.0002）。与健康对照组（p < 0.0001）和潜伏性结核感染个体（p = 0.0008）相比，活动性结核病患者在刺激 MAIT 细胞时用结核分枝杆菌裂解物/IL-15 刺激后 IFN-γ产生明显减少。从结核病患者和健康对照者中分离出的 MAIT 细胞的 RNA 测序鉴定出许多差异表达基因，并且编码 IFN-γ、TNF-α、IL-17F、颗粒酶 B 和颗粒酶的基因在结核病患者中表达均下调。与健康对照组相比，在 Mtb 裂解物/IL-15 刺激下，结核患者的 MAIT 细胞中 γc 受体的表达显著降低（p = 0.0028）。阻断 γc 和 IL-2Rβ 受体均导致 IFN-γ产生 MAIT 细胞的频率显著降低（79.4%）（p = 0.0011）。
结论
来自活动性结核病患者的 MAIT 细胞对结核分枝杆菌抗原表现出受损的细胞因子和细胞毒性反应。
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