A clonal model for human CD8+ regulatory T cells: unrestricted contact-dependent killing of activated CD4+ T cells.

A clonal model for human CD8+ regulatory T cells: unrestricted contact-dependent killing of activated CD4+ T cells.
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DOI:
10.1002/eji.201141618
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发表时间:
2012-01
影响因子:
5.4
通讯作者:
Ritz, Jerome
Ritz, Jerome
中科院分区:
医学3区
文献类型:
--
作者:
Hu, Dan;Liu, Xia;Zeng, Wanyong;Weiner, Howard L.;Ritz, Jerome

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先前对小鼠系统的研究表明,CD8+ Treg 细胞通过抑制活化的 CD4+ T 细胞来下调体内免疫反应。在这里,我们描述了在用自体 Epstein-Barr 病毒 (EBV) 特异性 CD4+ T 细胞体外刺激后从健康人外周血中分离出的新型调节性 CD8+ T 细胞克隆。 CD8+ Treg 细胞需要 TCR 激活 CD4+ 靶 T 细胞才能发挥抑制活性,这是通过以细胞接触依赖性方式裂解 CD4+ 靶标来介导的。抑制与 CD8+ Treg 细胞中的 Foxp3 表达、CD8+ Treg 细胞和 CD4+ 靶细胞之间的 HLA 相容性以及 CD4+ 靶 T 细胞的抗原特异性无关。 CD8+ Treg克隆表达CD3和多种TCR Vβ链以及CD56、CD69、CD62L和CD95,但不表达CD16、CD161、CXCR4和CCR7。当一起使用时,CD11a/CD18 和 CD8 特异性抗体可抑制 CD8+ Treg 克隆的抑制活性。建立在体外维持调节功能的克隆 CD8+ T 细胞的能力将有助于进一步研究在体内定义该群体并确定用于识别和抑制活化靶细胞的机制。
Previous studies in murine systems have demonstrated that CD8+ Treg cells down-regulate immune responses in vivo through suppressing activated CD4+ T cells. Here we describe novel regulatory CD8+ T-cell clones isolated from healthy human peripheral blood following in vitro stimulation with autologous Epstein–Barr virus (EBV)-specific CD4+ T cells. TCR activation of CD4+ target T cells was required for CD8+ Treg cells to exert suppressive activity, which was mediated through lysis of CD4+ targets in a cell contact-dependent manner. Suppression was independent of Foxp3 expression in CD8+ Treg cells, HLA compatibility between CD8+ Treg cells and CD4+ target cells and antigen-specificity of CD4+ target T cells. CD8+ Treg clones expressed CD3 and a variety of TCR Vβ chains as well as CD56, CD69, CD62L and CD95 but did not express CD16, CD161, CXCR4 and CCR7. When used together, antibodies specific for CD11a/CD18 and CD8 inhibited suppressive activity of CD8+ Treg clones. The ability to establish clonal CD8+ T cells that maintain regulatory function in vitro will facilitate further studies to define this population in vivo and to identify the mechanisms used for recognition and suppression of activated target cells.
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