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首页> 外文期刊>Immunity >Immunomodulatory Functions of BTLA and HVEM Govern Induction of Extrathymic Regulatory T Cells and Tolerance by Dendritic Cells
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Immunomodulatory Functions of BTLA and HVEM Govern Induction of Extrathymic Regulatory T Cells and Tolerance by Dendritic Cells

机译：BTLA和HVEM的免疫调节功能控制胸腺外调节性T细胞的诱导和树突状细胞的耐受性。

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Dendritic cells ( DCs) initiate immunity and also antigen-specific tolerance mediated by extrathymic regulatory T ( Treg) cells, yet it remains unclear how DCs regulate induction of such tolerance. Here, we report that efficient induction of Treg cells was instructed by BTLA(+)DEC205(+)CD8(+)CD11c(+)DCs and the immunomodulatory functions of BTLA. In contrast, T cell activation in steady state by total CD11c(+) DCs that include a majority of DCs that do not express BTLA did not induce Treg cells and had no lasting impact on subsequent immune responses. Engagement of HVEM, a receptor of BTLA, promoted Foxp3 expression in T cells through upregulation of CD5. In contrast, T cells activated in the absence of BTLA and HVEM-mediated functions remained CD5(lo) and therefore failed to resist the inhibition of Foxp3 expression in response to effector cell-differentiating cytokines. Thus, DCs require BTLA and CD5-dependent mechanisms to actively adjust tolerizing T cell responses under steady-state conditions.
机译：树突状细胞（DC）启动免疫，并由胸腺外调节性T（Treg）细胞介导的抗原特异性耐受性，但仍不清楚DC如何调节这种耐受性的诱导。在这里，我们报告说有效的Treg细胞诱导是由BTLA（+）DEC205（+）CD8（+）CD11c（+）DC和BTLA的免疫调节功能指导的。相反，包括总的不表达BTLA的DC在内的总CD11c（+）DC在稳态下激活T细胞不会诱导Treg细胞，并且对随后的免疫反应没有持久的影响。参与BTLA受体的HVEM的参与通过上调CD5促进了T细胞中Foxp3的表达。相反，在没有BTLA和HVEM介导的功能的情况下激活的T细胞仍为CD5（lo），因此无法抵抗对效应细胞分化的细胞因子的Foxp3表达的抑制。因此，DC需要BTLA和CD5依赖性机制来主动调节稳态条件下的耐受性T细胞应答。

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