Petzold Cathleen, Schallenberg Sonja, Stern Joel N H, Kretschmer Karsten
Immunotolerance in Regeneration, Center for Regenerative Therapies Dresden, Dresden, Germany.
Rev Diabet Stud. 2012 Winter;9(4):305-18. doi: 10.1900/RDS.2012.9.305. Epub 2012 Dec 28.
Dendritic cells (DCs) and Foxp3-expressing CD4⁺ regulatory T (Treg) cells play non-redundant roles in the maintenance of peripheral tolerance to self-antigens, thereby preventing fatal autoimmunity. A common hallmark of intra- and extra-thymic Treg cell lineage commitment is the induction of Foxp3 expression as a consequence of appropriate T cell receptor engagement with MHC class II:agonist ligand. It has now become increasingly clear that agonist ligand presentation by immature DCs in the steady state induces T cell tolerance by both recessive and dominant mechanisms, rather than promoting productive T helper cell responses. In this context, the ability of steady-state DCs to promote the extrathymic conversion of initially naïve CD4⁺Foxp3⁻ T cells into Foxp3⁺ Treg cells is of particular interest as it provides novel perspectives to enhance antigen-specific Treg cell function in clinical settings of unwanted immunity, such as β-cell autoimmunity.
树突状细胞（DCs）和表达Foxp3的CD4⁺调节性T（Treg）细胞在维持对外源自身抗原的外周耐受性中发挥着不可替代的作用，从而预防致命性自身免疫。胸腺内和胸腺外Treg细胞谱系定向的一个共同特征是，由于适当的T细胞受体与II类主要组织相容性复合体：激动剂配体结合，诱导Foxp3表达。现在越来越清楚的是，稳态下未成熟DCs呈递激动剂配体通过隐性和显性机制诱导T细胞耐受，而不是促进有效的辅助性T细胞应答。在这种情况下，稳态DCs促进初始幼稚CD4⁺Foxp3⁻T细胞向Foxp3⁺Treg细胞的胸腺外转化的能力尤其令人关注，因为它为在不需要的免疫临床环境（如β细胞自身免疫）中增强抗原特异性Treg细胞功能提供了新的视角。
