Immunity & infection
The SLAM family receptor 2B4 is mainly expressed on NK cells and memory CD8 T cells. In our previous research, we found that 2B4 was upregulated on both CD4+ and CD8+ T cells after sepsis induction in animals. Importantly, 2B4 on CD4+ T cells played the critical role in murine sepsis survival. However, the expression and functionality of 2B4 on human CD4+ T cells remain largely unclear. In this study, we investigate the expression, phenotype, and functionality of 2B4+CD4+ T cells isolated from septic patients and healthy donors. First, while no differences in 2B4 expression were observed on CD8+ T and NK cells, we found that CD4+ T cells isolated from human septic patients expressed significantly more 2B4 as compared to those obtained from healthy donors (P < 0.01). Notably, 2B4+CD4+ T cells isolated from septic patients were CCR7-CD45RA+ and displayed increased PD-1 and decreased ICOS and CD28 expression. Second, human 2B4+CD4+ T cells secreted less IL-2 and IFN-g following 6 hours of anti-CD3 anti-CD28 bead stimulation as compared to 2B4-CD4+ cells. Finally, 2B4-CD4+ and 2B4+ CD4+ subsets were sorted from healthy donor PBMC and stimulated with anti-CD3 and anti-CD28. 2B4+CD4+ cells were able to proliferate and maintained 2B4 expression, but had less proliferative capacity compared to 2B4-CD4+ cells. In conclusion, increased 2B4 expression was found on CD4+ T cells isolated from septic patients and these 2B4-expressing CD4+ T cells exhibited reduced cytokine secretion ability and proliferative capacity, suggesting 2B4 expression may compromise CD4+ T cell functionality during sepsis.