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

Eur J Immunol. 2014 Feb;44(2):420-30. doi: 10.1002/eji.201343572. Epub 2013 Dec 2.


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 T cells 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.

Keywords: Bacterial meningitis; Cerebrospinal fluid; Chemokines; Regulatory T (Treg) cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Cerebrospinal Fluid / immunology*
  • Chemotaxis / immunology*
  • Female
  • Granulocytes / immunology
  • Humans
  • Male
  • Meningitis, Bacterial / immunology*
  • Myeloid Cells / immunology*
  • Receptors, Chemokine / immunology
  • T-Lymphocytes, Regulatory / immunology*
  • Transforming Growth Factor beta / immunology


  • Receptors, Chemokine
  • Transforming Growth Factor beta