College of Health Sciences, Department of Medical Laboratory Science, Addis Ababa University, Addis Ababa, Ethiopia.
Armauer Hansen Research Institute, Addis Ababa, Ethiopia.
BMC Infect Dis. 2018 Sep 15;18(1):464. doi: 10.1186/s12879-018-3361-9.
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.
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.
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.
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.
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。
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。
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。
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。