In vivo costimulatory role of B7-DC in tuning T helper cell 1 and cytotoxic T lymphocyte responses.
In vivo costimulatory role of B7-DC in tuning T helper cell 1 and cytotoxic T lymphocyte responses.
复制标题
B7-DC在调整T辅助细胞1和细胞毒性T淋巴细胞反应中的体内共刺激作用。
DOI：
10.1084/jem.20050072
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发表时间：
2005-05-16
影响因子：
15.3
通讯作者：
Pardoll, Drew M
中科院分区：
文献类型：
--
作者：
Shin, Tahiro;Yoshimura, Kiyoshi;Shin, Takako;Crafton, Emily B;Tsuchiya, Haruo;Housseau, Franck;Koseki, Haruhiko;Schulick, Richard D;Chen, Lieping;Pardoll, Drew M
B7-DC是最近发现的B7家族成员之一，它通过与免疫受体酪氨酸抑制基序的抑制性PD-1受体结合来抑制T细胞的反应，并通过一种未知的共刺激受体增强T细胞的反应。B7-DC与共抑制B7家族成员B7-H1高度同源，B7-H1也与PD-1结合。目前尚不清楚B7-DC的哪种功能--共刺激或抑制--在体内起主导作用。为了研究B7-DC的体内功能，我们评估了B7-DC基因敲除(KO)小鼠的免疫应答。尽管没有被消除，但B7-DC KO小鼠的CD4T细胞产生的干扰素-γ(干扰素-γ)和依赖干扰素-γ的体液反应比野生型小鼠减少。B7-DC KO小鼠的抗原特异性CD8 T细胞反应和细胞毒性T淋巴细胞(CTL)活性也降低。B7-DC KO小鼠的肝肿瘤生长更快，与肝内肿瘤特异性CD8 T细胞的减少有关。这些结果强调了B7-DC和B7-H1在体内的不同作用，并表明B7-DC作为一个调谐分子，选择性地增强T辅助细胞1和CTL反应。
B7-DC, one of the recently described B7 family members, has the capacity to inhibit T cell responses via engagement of the immunoreceptor tyrosine-based inhibitory motif–containing inhibitory PD-1 receptor as well as enhance responses via an as yet unidentified costimulatory receptor. B7-DC is highly homologous to a coinhibitory B7 family member, B7-H1, which also binds PD-1. It is currently unclear which B7-DC function—costimulation or inhibition—predominates in vivo. To study in vivo functions of B7-DC, we evaluated immune responses in B7-DC knockout (KO) mice. Although not eliminated, interferon-γ (IFN-γ) production by CD4 T cells and IFN-γ–dependent humoral responses were reduced in B7-DC KO mice relative to wild type mice. Antigen-specific CD8 T cell responses and cytotoxic T lymphocyte (CTL) activity were also diminished in B7-DC KO mice. Hepatic tumors grew more quickly in B7-DC KO mice, associated with a decrease in intrahepatic tumor-specific CD8 T cells. These results highlight the contrasting in vivo roles of B7-DC and B7-H1 and indicate that B7-DC functions as a tuning molecule, selectively augmenting T helper 1 and CTL responses.