Tumor rejection induced by CD70-mediated quantitative and qualitative effects on effector CD8+ T cell formation.
Tumor rejection induced by CD70-mediated quantitative and qualitative effects on effector CD8+ T cell formation.
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DOI：
10.1084/jem.20031111
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发表时间：
2004-06-07
期刊：
影响因子：
--
通讯作者：
van Oers MH
中科院分区：
文献类型：
--
作者：
Arens R;Schepers K;Nolte MA;van Oosterwijk MF;van Lier RA;Schumacher TN;van Oers MH
抗原特异性CD 8 + T细胞的体内引发导致其扩增和分化成效应T细胞，随后收缩成可以终身维持的记忆T细胞群。最近的证据表明，在初始抗原刺激后，CD 8 + T细胞应答的幅度和动力学被编程。然而，目前还不清楚在何种程度上的CD 8 + T细胞的指令在体内调节的共刺激信号。在这里，我们证明，组成性连接的肿瘤坏死因子受体家族成员CD 27通过其配体CD 70定量增强CD 8 + T细胞对流感病毒感染和EL-4肿瘤的挑战，在体内增加初始扩增和维持较高数量的抗原特异性T细胞的记忆阶段。同时，抗原特异性T细胞的质量得到改善，如通过增加的干扰素（IFN）-γ产生和基于每个细胞的更大的细胞毒性潜力所证明的。作为一个明显的结果，由CD 70诱导的上级效应T细胞形成以CD 8 + T细胞和IFN-γ依赖性方式保护免受致死剂量的免疫原性差的EL 4肿瘤细胞。因此，CD 70共刺激增强抗原特异性CD 8 + T细胞的扩增和每细胞活性。
In vivo priming of antigen-specific CD8+ T cells results in their expansion and differentiation into effector T cells followed by contraction into a memory T cell population that can be maintained for life. Recent evidence suggests that after initial antigenic stimulation, the magnitude and kinetics of the CD8+ T cell response are programmed. However, it is unclear to what extent CD8+ T cell instruction in vivo is modulated by costimulatory signals. Here, we demonstrate that constitutive ligation of the tumor necrosis factor receptor family member CD27 by its ligand CD70 quantitatively augments CD8+ T cell responses to influenza virus infection and EL-4 tumor challenge in vivo by incrementing initial expansion and maintaining higher numbers of antigen-specific T cells in the memory phase. Concomitantly, the quality of antigen-specific T cells improved as evidenced by increased interferon (IFN)-γ production and a greater cytotoxic potential on a per cell basis. As an apparent consequence, the superior effector T cell formation induced by CD70 protected against a lethal dose of poorly immunogenic EL4 tumor cells in a CD8+ T cell– and IFN-γ–dependent manner. Thus, CD70 costimulation enhances both the expansion and per cell activity of antigen-specific CD8+ T cells.
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