Expansion of activated regulatory T cells by myeloid-specific chemokines via an alternative pathway in CSF of bacterial meningitis patients

Previous studies have demonstrated that activation/expansion by certain cytokines as well as recruitment by specific chemokines is involved in enrichment of regulatory T(Treg) cells in local tissues or organs under pathological conditions. Recent evidence indicates that human Treg cells are a heterogeneous population that comprises three distinct subpopulations: CD25(+)CD45RA(+) resting Treg (rTreg) cells, CD25(hi)CD45RA(-) activated Treg (aTreg) cells, which are both suppressive, and CD25(+)CD45RA(-) cytokine-secreting Tcells with proinflammatory capacity. Moreover, rTreg cells can proliferate and convert to aTreg cells. Here, we found an increase in aTreg-cell frequency in the cerebrospinal fluid (CSF) of patients with postneurosurgery bacterial meningitis. We revealed that such an increased aTreg-cell frequency in the CSF was not due to enhanced chemotaxis. Instead of a classic conversion pathway from rTreg to aTreg cells, we identified an alternative route of Treg-cell conversion from cytokine-secreting cells to aTreg cells induced by myeloid-specific chemokine CXC chemokine receptor (CXCR) ligand 5 via CXCR1 and CXCR2 receptors, or by CSF myeloid cells in a cell-cell contact manner. Our results reveal a different view of how the immune system controls overwhelming local immune responses during infection, and provide evidence of how innate immunity negatively regulates adaptive immunity.ImmunologySCI(E)0ARTICLEzhoujx.cn@gmail.com; zenghui@ccmu.edu.cn2420-4304