Expression of Costimulatory Ligand CD70 on Steady-State Dendritic Cells Breaks CD8+ T Cell Tolerance and Permits Effective Immunity
Expression of Costimulatory Ligand CD70 on Steady-State Dendritic Cells Breaks CD8+ T Cell Tolerance and Permits Effective Immunity
复制标题
DOI：
10.1016/j.immuni.2008.10.009
复制
发表时间：
2008-12-19
期刊：
影响因子：
32.4
通讯作者：
Borst, Jannie
中科院分区：
文献类型：
--
作者：
Keller, Anna M.;Schildknecht, Anita;Borst, Jannie
稳定状态的树突状细胞(DC)维持外周T细胞耐受，而成熟的DC产生免疫。CD70是DC成熟后获得的一种共刺激配体。为了确定其对T细胞命运的影响，我们培育了在常规DC(CDCs)中结构性表达CD70的小鼠。在这些小鼠中，幼稚的CD4(+)和CD8(+)T细胞自发地转化为效应细胞。给予无佐剂的多肽，通常是耐受性的，可诱发肿瘤根除CD8(+)T细胞反应和强大的CD4(+)T细胞非依赖性记忆。CD70在可诱导呈现病毒表位的CDC中也有结构性表达。在这种情况下，耐受性诱导也被阻止了。抗原提呈树突状细胞对病毒感染产生保护性免疫，打破了CD8(+)T细胞的耐受状态。因此，CD70的唯一表达足以将CD8(+)T细胞耐受转化为免疫，从而定义了CD27-CD70相互作用在T细胞和DC之间界面的重要性。
Steady-state dendritic cells (DCs) maintain peripheral T cell tolerance, whereas mature DCs generate immunity. CD70 is a costimulatory ligand acquired upon DC maturation. To determine its impact on T cell fate, we have generated mice that constitutively express CD70 in conventional DCs (cDCs). In these mice, naive CD4(+) and CD8(+) T cells spontaneously convert into effector cells. Administration of peptide without adjuvant, which is ordinarily tolerogenic, elicited tumor-eradicating CD8(+) T cell responses and robust CD4(+) T cell-independent memory. CD70 was also constitutively expressed in cDCs that inducibly present viral epitopes. In this case, tolerance induction was prevented as well. The antigen-presenting DCs generated protective immunity to virus infection and broke a pre-existing state of CD8(+) T cell tolerance. Thus, the sole expression of CD70 by otherwise immature cDCs sufficed to convert CD8(+) T cell tolerance into immunity, defining the importance of CD27-CD70 interactions at the interface between T cell and DC.