title: Expansion of activated regulatory T cells by myeloid-specific chemokines via an alternative pathway in CSF of bacterial meningitis patients.
abstract: 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.
authors.affiliation: Intensive Care Unit, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Guangzhi
authors.initials: G
authors.lastname: Shi
authors.forename: Junyan
authors.initials: J
authors.lastname: Han
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Hao
authors.forename: Yaluan
authors.initials: Y
authors.lastname: Ma
authors.forename: Tong
authors.initials: T
authors.lastname: Li
authors.forename: Xueying
authors.initials: X
authors.lastname: Wu
authors.forename: Henghui
authors.initials: H
authors.lastname: Zhang
authors.forename: Yanan
authors.initials: Y
authors.lastname: Liu
authors.forename: Beibei
authors.initials: B
authors.lastname: Wang
authors.forename: Yaxian
authors.initials: Y
authors.lastname: Kong
authors.forename: Jianxin
authors.initials: J
authors.lastname: Zhou
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
mesh_terms: D000328:Adult; D002555:Cerebrospinal Fluid / Q000276:immunology*; D002633:Chemotaxis / Q000276:immunology*; D005260:Female; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D008297:Male; D016920:Meningitis, Bacterial / Q000276:immunology*; D022423:Myeloid Cells / Q000276:immunology*; D019707:Receptors, Chemokine / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology
chemical_list: D019707:Receptors, Chemokine; D016212:Transforming Growth Factor beta
keywords: Bacterial meningitis; Cerebrospinal fluid; Chemokines; Regulatory T (Treg) cells