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

Background: Previous studies reported HIV infection alters the distribution and function of gamma delta T cells and their subsets. gamma delta T phenotypes in healthy and diseased individuals has received little attention in Ethiopia. We conducted this study to analyze the distribution of gamma delta 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 gamma delta T cells, V delta 1 and V delta 2 T cells subsets were analyzed in clinical samples collected from asymptomatic HIV, pulmonary TB patients and apparently healthy controls. Multicolor flow cytometry and IFN-gamma ELISA were used to assess surface markers and functional responses of V delta 2 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 gamma delta T cells and in the proportion of V delta 1 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 V delta 2 T cells, as well as the IFN-gamma 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 (alpha E beta 7) were significantly higher in the V delta 1 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-) V delta 2 T cell subsets in HIV negative pulmonary TB patients. Conclusion: In sum, HIV infection was associated with an increase in V delta 1 and a decrease in the function and frequencies of V delta 2 T cells. Moreover, increased effector V delta 2 T cells were observed among HIV negative pulmonary TB patients suggesting a potential role of these T cells in the host response to TB.