Immunity:树突细胞指导T细胞发挥作用的新型分子机制

Immunomodulatory Functions of BTLA and HVEM Govern Induction of Extrathymic Regulatory T Cells and Tolerance by Dendritic Cells

日前。刊登在国际杂志Immunity上的一项研究报告中，来自圣路易斯大学（Saint Louis University）的研究人员通过研究揭示了机体免疫系统中的树突细胞如何指挥T淋巴细胞学习对机体自身细胞的耐受性。机体免疫系统往往会通过避免过度反应或反应不足所带来的危险来维持机体健康，

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 CD5lo 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.