Frequency and functional profile of circulating TCRαβ⁺ double negative T cells in HIV/TB co-infection

Background: Increased frequency of circulating double negative T (DNT, CD4^-CD8^-CD3⁺) cells with protective immune function has been observed in human immunodeficiency virus (HIV) infection and tuberculosis (TB). Here the role of circulating TCRαβ⁺ DNT cells was further investigated in HIV/TB co-infection.

Methods: A cross-sectional study was conducted to investigate the frequency and functional profiles of peripheral TCRαβ⁺ DNT cells including apoptosis, chemokine and cytokine expression among healthy individuals and patients with TB, HIV infection and HIV/TB co-infection by cell surface staining and intracellular cytokine staining combined with flow cytometry.

Results: Significantly increased frequency of TCRαβ⁺ DNT cells was observed in HIV/TB co-infection than that in TB (p < 0.001), HIV infection (p = 0.039) and healthy controls (p < 0.001). Compared with TB, HIV/TB co-infection had higher frequency of Fas expression (p = 0.007) and lower frequency of Annexin V expression on TCRαβ⁺ DNT cells (p = 0.049), and the frequency of Annexin V expression on Fas⁺TCRαβ⁺ DNT cells had no significant difference. TCRαβ⁺ DNT cells expressed less CCR5 in HIV/TB co-infection than that in TB (p = 0.014), and more CXCR4 in HIV/TB co-infection than that in HIV infection (p = 0.043). Compared with healthy controls, TB and HIV/TB co-infection had higher frequency of TCRαβ⁺ DNT cells secreting Granzyme A (p = 0.046; p = 0.005). In TB and HIV/TB co-infection, TCRαβ⁺ DNT cells secreted more granzyme A (p = 0.002; p = 0.002) and perforin (p < 0.001; p = 0.017) than CD4⁺ T cells but similar to CD8⁺ T cells.

Conclusions: Reduced apoptosis may take part in the mechanism of increased frequency of peripheral TCRαβ⁺ DNT cells in HIV/TB co-infection. TCRαβ⁺ DNT cells may play a cytotoxic T cells-like function in HIV/TB co-infection.