The characteristic profiles of PD-1 and PD-L1 expressions and dynamic changes during treatment in active tuberculosis

The characteristic profiles of PD-1 and PD-L1 expressions and dynamic changes during treatment in active tuberculosis
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活动性结核病PD-1和PD-L1表达特征及治疗过程中的动态变化

DOI:
10.1016/j.tube.2016.10.001
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发表时间:
2016-12-01
期刊:
影响因子:
3.2
通讯作者:
Shao, Lingyun
Shao, Lingyun
中科院分区:
医学4区
文献类型:
--
作者:
Shen, Lei;Shi, Hong;Shao, Lingyun

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PD-1是活化的T、B淋巴细胞的细胞表面受体,其在结核病中的作用存在争议,因为临床研究与动物模型缺乏一致性。为探讨结核病的免疫发病机制,寻找防治结核病的免疫治疗靶点,本研究探讨了PD-1/PD-L1通路在不同CD 4 +T细胞亚群中的表达特点及动态变化。我们招募了24名人类受试者,包括15名活动性结核病(ATB)患者和9名健康供体(HD)。ATB患者CD 4 +T细胞PD-1和PD-L1表达较HD患者明显升高。ATB患者的调节性T细胞(Treg,CD 4(+)CD 25 + Foxp 3+)比例高于HD。PD-1和PD-L1在Treg细胞、Tresp(CD 4(+)CD 25)细胞和Teff(CD 4(+)CD 25 + Foxp 3-)细胞上的表达显著增加。最后,有效抗TB治疗后的临床改善与Tresp和Teff细胞中PD-1表达的显著降低相关,但与Treg细胞中的PD-1表达无关。因此,PD-1在T细胞亚群中的表达谱可用作预测抗结核治疗的临床疗效的候选者。调节PD-1/13 D-L1通路在CD 4亚群中的表达可能为结核病的控制提供一个免疫治疗靶点。(C)2016爱思唯尔有限公司版权所有
PD-1 is a cell surface receptor of activated T and B lymphocytes and it's role in tuberculosis is controversial because of lack of congruence between clinical study and animal model. To investigate the immunological pathogenesis mechanisms of tuberculosis and to develop the immune therapy target essential for controlling tuberculosis, here we explored the expression characteristics and dynamic changes of PD-1/PD-L1 pathway in different CD4+T cell subsets. We enrolled 24 human subjects including 15 active tuberculosis (ATB) patients and 9 healthy donors (HD). The expressions of PD-1 and PD-L1 on CD4+T cells increased significantly in ATB patients than HD. ATB patients had a higher proportion of regulatory T cells (Treg, CD4(+)CD25 + Foxp3+) than HD. The expressions of PD-1 and PD-L1 increased remarkably on CD4+T cell subsets, including Treg cells, Tresp (CD4(+)CD25) cells and Teff (CD4(+)CD25 + Foxp3-) cells. Finally, clinical improvement following effective anti-TB therapy is correlated with significantly decreased expression of PD-1 in Tresp and Teff cells, but not in Treg cells. Thus, expression profiles of PD-1 in T cell subpopulations may be used as a candidate to predict the clinical efficacy of anti-tuberculosis therapy. Modulation of PD-1/13D-L1 pathway in CD4 subsets may offer an immunotherapy target for the control of tuberculosis. (C) 2016 Elsevier Ltd. All rights reserved.