Identification of tonsillar CD4±CD25=LAG3± T cells as naturally occurring IL-10-producing regulatory T cells in human lymphoid tissue.
Identification of tonsillar CD4±CD25=LAG3± T cells as naturally occurring IL-10-producing regulatory T cells in human lymphoid tissue.
复制标题
将扁桃体 CD4±CD25=LAG3± T 细胞鉴定为人淋巴组织中天然存在的产生 IL-10 的调节性 T 细胞。
DOI：
10.1016/j.jaut.2016.09.005
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Fujio K.
中科院分区：
文献类型：
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作者：
Sumitomo S;Nakachi S;Okamura T;Tsuchida Y;Kato R;Shoda H;Furukawa A;Kitahara N; Kondo K;Yamasoba T;Yamamoto K;Fujio K.
产生IL-10的调节性T细胞（IL-10-producing regulatory T cells，IL-10-producing Tcells）是调节性T细胞亚群之一，其特征在于产生大量IL-10、缺乏FOXP 3表达和强免疫抑制能力。到目前为止，产生IL-10的Tcl 3主要被报道为诱导的群体，部分原因是由于缺乏确定的表面标志物，鉴定天然存在的产生IL-10的Tcl 3是困难的。淋巴细胞活化基因3（LAG 3）是一种CD 4同源物，我们已经确定其在产生IL-10的T细胞上表达。在人PBMC中，LAG 3与CD 49 b的组合有效地鉴定产生IL-10的TcB。然而，在人类次级淋巴组织中天然产生IL-10的T细胞还没有被描述。在这份报告中，我们在人类扁桃体中鉴定了CD 4 + CD 25 − LAG 3 +T细胞。这种T细胞亚群产生大量的IL-10，并表达低水平的FOXP 3。表面标记和微阵列分析显示，这是一个独特的扁桃体CD 4 +T细胞亚群。CD 4 + CD 25 − LAG 3 +T细胞高水平表达白细胞介素10（IL 10）、PR/SET结构域1（PRDM 1）和CD 274，低水平表达趋化因子受体5（CXCR 5）。CD 4 + CD 25 − LAG 3 +T细胞比CD 4 + CD 25 +T细胞更有效地抑制抗体产生，并且CD 4 + CD 25 − LAG 3 +T细胞诱导B细胞凋亡。此外，对人源化小鼠的分析显示，该细胞亚群抑制体内移植物抗宿主病（GVHD）反应。我们的研究揭示了人次级淋巴组织中天然存在的产生IL-10的T细胞的存在及其在免疫调节中的功能。
IL-10-producing regulatory T cells (IL-10-producing Tregs) are one of the regulatory T cell subsets characterized by the production of high amounts of IL-10, the lack of FOXP3 expression and the strong immunosuppressive capabilities. IL-10-producing Tregs have been primarily reported as induced populations thus far, in part because identifying naturally occurring IL-10-producing Tregs was difficult due to the lack of definitive surface markers. Lymphocyte-activation gene 3 (LAG3) is a CD4 homologue that we have identified as being expressed on IL-10 producing Tregs. In human PBMC, LAG3 combined with CD49b efficiently identifies IL-10-producing Tregs. However, naturally occurring IL-10-producing Tregs in human secondary lymphoid tissue have not been described.In this report, we identified CD4+CD25−LAG3+T cells in human tonsil. This T cell subset produced high amounts of IL-10 and expressed low levels of FOXP3. Surface markers and microarray analysis revealed that this is a distinct tonsillar CD4+T cell subset. CD4+CD25−LAG3+T cells expressed interleukin 10 (IL10), PR/SET domain 1 (PRDM1), and CD274 at high levels and chemokine receptor 5 (CXCR5) at low levels. CD4+CD25−LAG3+T cells suppressed antibody production more efficiently than CD4+CD25+T cells, and CD4+CD25−LAG3+T cells induced B cell apoptosis. Moreover, analysis of humanized mice revealed that this cell subset suppressed a graft-versus-host disease (GVHD) reactionin vivo. Our study reveals the existence of naturally occurring IL-10-producing Tregs in human secondary lymphoid tissue and their function in immune regulation.