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埃塞俄比亚亚的斯亚贝巴的肺结核和 HIV 患者外周 γδ T 细胞的表型和功能异质性。

Phenotypic and functional heterogeneity of peripheral γδ T cells in pulmonary TB and HIV patients in Addis Ababa, Ethiopia.

机构信息

College of Health Sciences, Department of Medical Laboratory Science, Addis Ababa University, Addis Ababa, Ethiopia.

Armauer Hansen Research Institute, Addis Ababa, Ethiopia.

出版信息

BMC Infect Dis. 2018 Sep 15;18(1):464. doi: 10.1186/s12879-018-3361-9.

Abstract

BACKGROUND

Previous studies reported HIV infection alters the distribution and function of γδ T cells and their subsets. γδ T phenotypes in healthy and diseased individuals has received little attention in Ethiopia. We conducted this study to analyze the distribution of γδ T cells, the subsets and levels of expression of activation (CD38), exhaustion or anergy (CD95, PD1), adhesion (N-CAM/CD56 and CD103), among HIV and TB infected patients.

METHOD

The distributions of total γδ T cells, Vδ1 and Vδ2 T cells subsets were analyzed in clinical samples collected from asymptomatic HIV, pulmonary TB patients and apparently healthy controls. Multicolor flow cytometry and IFN-γ ELISA were used to assess surface markers and functional responses of Vδ2 T cells to isopentenyl pyrophosphate stimulation, respectively.

RESULT

A total of 52 study participants were enrolled in this study, 22 HIV + TB-, 10 HIV-TB+ and 20 healthy controls. No significant differences were observed in the distribution of total γδ T cells and in the proportion of Vδ1 subsets in all study groups, though slightly higher proportions were observed in HIV + TB- patients for the latter, of borderline statistical significance (p = 0.07). However, the proportion of Vδ2 T cells, as well as the IFN-γ response to IPP stimulation, was significantly reduced in HIV + TB- patients compared to healthy controls (p < 0.002). Expression of the activation marker CD38 (p < 0.001) and adhesion marker CD103 (αEβ7) were significantly higher in the Vδ1 T cell subset among both HIV + TB- (p = 0.013) and HIV-TB+ (p = 0.006) patients compared to healthy controls. Similarly, exhaustion markers, CD95 and PD1, were significantly higher in these two T cell subsets among both HIV + TB- and HIV-TB+ patients (p < 0.01). Interestingly, we also observed an increased proportion of effector memory (CD45RA-CD27-) and effector cytotoxic (CD45RA + CD27-) Vδ2 T cell subsets in HIV negative pulmonary TB patients.

CONCLUSION

In sum, HIV infection was associated with an increase in Vδ1 and a decrease in the function and frequencies of Vδ2 T cells. Moreover, increased effector Vδ2 T cells were observed among HIV negative pulmonary TB patients suggesting a potential role of these T cells in the host response to TB.

摘要

背景

先前的研究表明,HIV 感染改变了 γδ T 细胞及其亚群的分布和功能。在埃塞俄比亚,人们对健康和患病个体的 γδ T 表型关注甚少。我们进行了这项研究,以分析 HIV 和结核感染患者中 γδ T 细胞、亚群的分布以及激活(CD38)、衰竭或无能(CD95、PD1)、黏附(N-CAM/CD56 和 CD103)标志物的表达水平。

方法

分析了来自无症状 HIV、肺结核患者和健康对照的临床样本中总 γδ T 细胞、Vδ1 和 Vδ2 T 细胞亚群的分布。多色流式细胞术和 IFN-γ ELISA 分别用于评估 Vδ2 T 细胞对异戊烯焦磷酸刺激的表面标志物和功能反应。

结果

本研究共纳入 52 名研究参与者,其中 22 名 HIV+TB-、10 名 HIV-TB+和 20 名健康对照。在所有研究组中,总 γδ T 细胞的分布和 Vδ1 亚群的比例均无显著差异,但 HIV+TB-患者的 Vδ1 亚群比例略高,具有边缘统计学意义(p=0.07)。然而,与健康对照组相比,HIV+TB-患者的 Vδ2 T 细胞比例以及对 IPP 刺激的 IFN-γ 反应显著降低(p<0.002)。在 HIV+TB-和 HIV-TB+患者中,Vδ1 T 细胞亚群的激活标志物 CD38(p<0.001)和黏附标志物 CD103(αEβ7)的表达均显著升高(p=0.013)。同样,在这两个 T 细胞亚群中,衰竭标志物 CD95 和 PD1 的表达在 HIV+TB-和 HIV-TB+患者中均显著升高(p<0.01)。有趣的是,我们还观察到 HIV 阴性肺结核患者中效应记忆(CD45RA-CD27-)和效应细胞毒性(CD45RA+CD27-)Vδ2 T 细胞亚群的比例增加。

结论

总之,HIV 感染与 Vδ1 的增加和 Vδ2 T 细胞功能和频率的降低有关。此外,在 HIV 阴性肺结核患者中观察到效应 Vδ2 T 细胞增加,这表明这些 T 细胞在宿主对结核的反应中可能发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/792c/6139120/c00aa7afba0f/12879_2018_3361_Fig1_HTML.jpg

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