Faculty of Medicine, Department of Dermatology, University of Yamanashi, Yamanashi, Japan.
J Invest Dermatol. 2011 Jun;131(6):1252-61. doi: 10.1038/jid.2011.36. Epub 2011 Apr 14.
The interaction between CD27 and CD70 provides a costimulatory signal for T-cell survival. Although the role of CD27 signaling in CD8(+) T cells has been well defined, its role in CD4(+) T cells is relatively unknown. Here, we report that CD70 is specifically expressed on differentiated T-helper (Th)1 cells, but not on Th2 cells. Upon activation, CD70 expression increased markedly on Th1 cells, but remained undetectable on Th2 cells. We demonstrate that CD27 is involved in naive T-cell expansion in Th1-type, but not in Th2-type, immune responses as in vivo treatment with anti-CD70 monoclonal antibody at induction resulted in a significant reduction of delayed-type and contact hypersensitivity responses, but not asthmatic responses. In both Th1-type responses, during the priming phase, CD70 was detected at earlier time points on dendritic cells (DCs) and at later time points on CD4(+) T cells. Our results indicate that CD70 may be useful as a marker to distinguish Th1 from Th2 cells. More importantly, CD27 function may be controlled by the differentially regulated kinetics of CD70 expression on DCs and CD4(+) T cells, and Th1 cell-specific CD70 expression may be involved in an amplification loop for polarized Th1-type immune responses through T cell-T cell interactions.
CD27 与 CD70 的相互作用为 T 细胞的存活提供了一个共刺激信号。虽然 CD27 信号在 CD8(+)T 细胞中的作用已得到很好的定义,但它在 CD4(+)T 细胞中的作用相对未知。在这里,我们报告说 CD70 特异性地表现在分化的辅助性 T 细胞(Th)1 细胞上,而不在 Th2 细胞上。在激活后,Th1 细胞上的 CD70 表达显著增加,但在 Th2 细胞上仍无法检测到。我们证明 CD27 参与 Th1 型而非 Th2 型免疫反应中的初始 T 细胞扩增,因为在诱导时体内用抗 CD70 单克隆抗体治疗导致迟发型和接触超敏反应显著减少,但哮喘反应不受影响。在这两种 Th1 型反应中,在启动阶段,CD70 更早地在树突状细胞(DC)上检测到,而在稍后时间在 CD4(+)T 细胞上检测到。我们的结果表明,CD70 可作为区分 Th1 和 Th2 细胞的标记物。更重要的是,CD27 功能可能受到 DC 和 CD4(+)T 细胞上 CD70 表达的差异调节动力学的控制,而 Th1 细胞特异性 CD70 表达可能通过 T 细胞-T 细胞相互作用参与极化 Th1 型免疫反应的扩增环。