Jones Andrew, Bourque Jessica, Kuehm Lindsey, Opejin Adeleye, Teague Ryan M, Gross Cindy, Hawiger Daniel
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104, USA.
Immunity. 2016 Nov 15;45(5):1066-1077. doi: 10.1016/j.immuni.2016.10.008. Epub 2016 Oct 25.
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 BTLADEC205CD8CD11c 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 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.
树突状细胞（DCs）启动免疫反应，同时也介导由胸腺外调节性T（Treg）细胞介导的抗原特异性耐受，但DCs如何调节这种耐受的诱导仍不清楚。在此，我们报告BTLADEC205CD8CD11c DCs指导Treg细胞的有效诱导以及BTLA的免疫调节功能。相比之下，包括大多数不表达BTLA的DCs在内的总CD11c DCs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影响。BTLA的受体HVEM的结合通过上调CD5促进T细胞中Foxp3的表达。相比之下，在没有BTLA和HVEM介导功能的情况下激活的T细胞仍然是CD5，因此在响应效应细胞分化细胞因子时无法抵抗Foxp3表达的抑制。因此，DCs需要BTLA和CD5依赖性机制在稳态条件下积极调节耐受T细胞反应。
