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.