免疫系统
周边公差
生物
免疫耐受
外围设备
免疫学
克隆缺失
细胞生物学
癌症研究
T细胞
医学
T细胞受体
内科学
作者
Jikai Cui,Heng Xu,Jizhang Yu,Shen Ran,Xi Zhang,Yuan Li,Zhang Chen,Yuqing Niu,Song Wang,Weicong Ye,Wenhao Chen,Jie Wu,Jiahong Xia
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2024-04-26
卷期号:9 (94)
标识
DOI:10.1126/sciimmunol.adh0085
摘要
Thymic negative selection of the T cell receptor (TCR) repertoire is essential for establishing self-tolerance and acquired allograft tolerance following organ transplantation. However, it is unclear whether and how peripheral clonal deletion of alloreactive T cells induces transplantation tolerance. Here, we establish that programmed cell death protein 1 (PD-1) is a hallmark of alloreactive T cells and is associated with clonal expansion after alloantigen encounter. Moreover, we found that diphtheria toxin receptor (DTR)–mediated ablation of PD-1 + cells reshaped the TCR repertoire through peripheral clonal deletion of alloreactive T cells and promoted tolerance in mouse transplantation models. In addition, by using PD-1–specific depleting antibodies, we found that antibody-mediated depletion of PD-1 + cells prevented heart transplant rejection and the development of experimental autoimmune encephalomyelitis (EAE) in humanized PD-1 mice. Thus, these data suggest that PD-1 is an attractive target for peripheral clonal deletion and induction of immune tolerance.
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