Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Laboratory Medicine, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, China.
Int J Infect Dis. 2018 Sep;74:1-9. doi: 10.1016/j.ijid.2018.06.011. Epub 2018 Jun 21.
CD4CXCR5 T cells have previously been established. However, their decreased frequency during tuberculosis (TB) disease is only partially understood. The aim of this study was to explore the depletion of CD4CXCR5 T cells in human TB.
The frequency and function of CD4CXCR5 T cells were evaluated in active TB (ATB) patients and healthy control subjects. The function of CD4CXCR5 T cells was determined after blockade of inhibitory receptors.
The frequency of CD4CXCR5 T cells was decreased in ATB patients. The expression of activation markers (HLA-DR and ICOS) and inhibitory receptors (Tim-3 and PD-1) on CD4CXCR5 T cells was increased in the ATB group. TB-specific antigen stimulation induced higher expression of inhibitory receptors than phytohemagglutinin stimulation in the ATB group. In contrast, TB antigen stimulation did not induce a significantly increased expression of IL-21 and Ki-67 on CD4CXCR5 T cells. However, blockade of inhibitory receptors Tim-3 and PD-1 not only increased the frequency of CD4CXCR5 T cells, but also restored their proliferation and cytokine secretion potential.
The increased expression of inhibitory receptors involves the depletion of CD4CXCR5 T cells, and blockade of inhibitory receptors can restore the function of CD4CXCR5 T cells in ATB patients.
CD4CXCR5 T 细胞此前已被确定。然而，它们在结核病（TB）疾病期间的频率降低仅部分得到理解。本研究旨在探讨人类 TB 中 CD4CXCR5 T 细胞耗竭的情况。
在活动性 TB（ATB）患者和健康对照者中评估 CD4CXCR5 T 细胞的频率和功能。在抑制性受体被阻断后，测定 CD4CXCR5 T 细胞的功能。
ATB 患者中 CD4CXCR5 T 细胞的频率降低。ATB 组 CD4CXCR5 T 细胞的激活标志物（HLA-DR 和 ICOS）和抑制性受体（Tim-3 和 PD-1）的表达增加。TB 特异性抗原刺激比植物血球凝集素刺激在 ATB 组中诱导更高的抑制性受体表达。相比之下，TB 抗原刺激并未导致 CD4CXCR5 T 细胞上的 IL-21 和 Ki-67 表达显著增加。然而，抑制性受体 Tim-3 和 PD-1 的阻断不仅增加了 CD4CXCR5 T 细胞的频率，而且还恢复了它们的增殖和细胞因子分泌潜能。
抑制性受体的表达增加涉及 CD4CXCR5 T 细胞的耗竭，并且抑制性受体的阻断可以恢复 ATB 患者中 CD4CXCR5 T 细胞的功能。
