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 TCR alpha beta+ 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 TCR alpha beta(+) 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 TCR alpha beta(+) 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 TCR alpha beta(+) DNT cells (p = 0.049), and the frequency of Annexin V expression on Fas(+)TCR alpha beta(+) DNT cells had no significant difference. TCR alpha beta(+) 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 TCR alpha beta(+) DNT cells secreting Granzyme A (p = 0.046; p = 0.005). In TB and HIV/TB co-infection, TCR alpha beta(+) 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 TCR alpha beta(+) DNT cells in HIV/TB co-infection. TCR alpha beta(+) DNT cells may play a cytotoxic T cells-like function in HIV/TB co-infection.

Automated summary

The frequency of peripheral TCR alpha beta(+) DNT cells is increased in HIV/TB co-infection, and reduced apoptosis may contribute to this increase. TCR alpha beta(+) DNT cells may play a cytotoxic T cells-like function in HIV/TB co-infection.