Expansion of activated regulatory T cells by myeloid-specific chemokines via an alternative pathway in CSF of bacterial meningitis patients
Expansion of activated regulatory T cells by myeloid-specific chemokines via an alternative pathway in CSF of bacterial meningitis patients
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DOI：
10.1002/eji.201343572
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发表时间：
2014-02-01
影响因子：
5.4
通讯作者：
Zeng, Hui
中科院分区：
文献类型：
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作者：
Shi, Guangzhi;Han, Junyan;Zeng, Hui
先前的研究已经证明，某些细胞因子的激活/扩增以及特定趋化因子的募集参与了病理条件下局部组织或器官中调节性T（Treg）细胞的富集。最近的证据表明，人Treg细胞是一种异质性群体，其包含三种不同的亚群：CD25（+）CD45RA（+）静息Treg（rTreg）细胞、CD25（hi）CD45RA（-）活化Treg（aTreg）细胞（两者都是抑制性的）和具有促炎能力的分泌CD25（+）CD45RA（-）亮氨酸的T细胞。此外，rTreg细胞可以增殖并转化为aTreg细胞。在这里，我们发现了增加aTreg细胞的频率在脑脊液（CSF）的患者神经外科手术后细菌性脑膜炎。我们发现CSF中aTreg细胞频率的增加不是由于趋化性增强。代替从rTreg到aTreg细胞的经典转化途径，我们鉴定了由骨髓特异性趋化因子CXC趋化因子受体（CXCR）配体5经由CXCR 1和CXCR 2受体或由CSF骨髓细胞以细胞-细胞接触方式诱导的Treg-细胞从精氨酸分泌细胞向aTreg细胞转化的替代途径。我们的研究结果揭示了免疫系统如何在感染期间控制压倒性的局部免疫反应的不同观点，并提供了先天免疫如何负调节适应性免疫的证据。
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.