Tissue expression of PD-L1 mediates peripheral T cell tolerance.
Tissue expression of PD-L1 mediates peripheral T cell tolerance.
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PD-L1的组织表达介导外周T细胞耐受性。
DOI：
10.1084/jem.20051776
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发表时间：
2006-04-17
影响因子：
15.3
通讯作者：
Sharpe, AH
中科院分区：
文献类型：
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作者：
Keir, ME;Liang, SC;Guleria, I;Latchman, YE;Qipo, A;Albacker, LA;Koulmanda, M;Freeman, GJ;Sayegh, MH;Sharpe, AH
程序性死亡1（PD-1）是一种在活化的淋巴细胞上表达的抑制性受体，调节耐受和自身免疫。PD-1有两个配体：PD-1配体1（PD-L1），广泛表达于造血和实质细胞，包括胰岛细胞;以及PD-L2，仅限于巨噬细胞和树突细胞。为了研究PD-L1和PD-L2在调节T细胞活化和耐受性方面是否具有协同作用或独特作用，我们产生了缺乏PD-L1和PD-L2的小鼠（PD-L1/PD-L2−/−小鼠），并将其与缺乏PD-L的小鼠进行了比较。PD-L1和PD-L2在抑制T细胞活化过程中白细胞介素-2和干扰素-γ产生方面具有重叠功能。然而，PD-L1在控制胰腺中的自身反应性T细胞方面具有独特而关键的作用。我们对骨髓嵌合体的研究表明，仅在抗原呈递细胞上表达PD-L1/PD-L2不足以预防PD-L1/PD-L2−/−非肥胖糖尿病小鼠中发生的早发性糖尿病。PD-L1在胰岛中的表达可保护同基因胰岛移植到糖尿病受体后的免疫病理学。PD-L1抑制致病性自身反应性CD 4 + T细胞介导的组织破坏和效应细胞因子的产生。这些数据提供了PD-L1在实质细胞而不是造血细胞上表达的证据，可以预防自身免疫性糖尿病，并指出PD-1-PD-L1相互作用在介导组织耐受中的新作用。
Programmed death 1 (PD-1), an inhibitory receptor expressed on activated lymphocytes, regulates tolerance and autoimmunity. PD-1 has two ligands: PD-1 ligand 1 (PD-L1), which is expressed broadly on hematopoietic and parenchymal cells, including pancreatic islet cells; and PD-L2, which is restricted to macrophages and dendritic cells. To investigate whether PD-L1 and PD-L2 have synergistic or unique roles in regulating T cell activation and tolerance, we generated mice lacking PD-L1 and PD-L2 (PD-L1/PD-L2−/− mice) and compared them to mice lacking either PD-L. PD-L1 and PD-L2 have overlapping functions in inhibiting interleukin-2 and interferon-γ production during T cell activation. However, PD-L1 has a unique and critical role in controlling self-reactive T cells in the pancreas. Our studies with bone marrow chimeras demonstrate that PD-L1/PD-L2 expression only on antigen-presenting cells is insufficient to prevent the early onset diabetes that develops in PD-L1/PD-L2−/− non-obese diabetic mice. PD-L1 expression in islets protects against immunopathology after transplantation of syngeneic islets into diabetic recipients. PD-L1 inhibits pathogenic self-reactive CD4+ T cell–mediated tissue destruction and effector cytokine production. These data provide evidence that PD-L1 expression on parenchymal cells rather than hematopoietic cells protects against autoimmune diabetes and point to a novel role for PD-1–PD-L1 interactions in mediating tissue tolerance.
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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。
影响因子：
15.3
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
通讯作者：
Pardoll, Drew M
影响因子：
32.4
作者：
Dong, HD;Zhu, GF;Chen, LP
通讯作者：
Chen, LP
影响因子：
30.5
作者：
Latchman, Y;Wood, CR;Freeman, GJ
通讯作者：
Freeman, GJ
影响因子：
6.1
作者：
Schoop, R;Wahl, P;Wüthrich, RP
通讯作者：
Wüthrich, RP
DOI：
10.1084/jem.184.5.2049
发表时间：
1996-11-01
期刊：
The Journal of experimental medicine
影响因子：
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作者：
通讯作者：
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