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人类小肠和结肠中的Vδ1 T细胞受体库。

The V delta 1 T cell receptor repertoire in human small intestine and colon.

作者信息

Chowers Y, Holtmeier W, Harwood J, Morzycka-Wroblewska E, Kagnoff M F

机构信息

Department of Medicine, University of California at San Diego, La Jolla 92093-0623.

出版信息

J Exp Med. 1994 Jul 1;180(1):183-90. doi: 10.1084/jem.180.1.183.

Abstract

V delta 1 bearing T cells comprise the major population of gamma/delta T cells in the human intestinal tract. To gain insight into mechanisms involved in the generation of these cells and the diversity of their repertoire, we have characterized the junctional sequences of V delta 1 T cell receptor transcripts in the human small intestine and colon. Mucosal biopsies obtained from defined regions along the length of the small intestine or colon contained a high frequency of either one or a few identical in frame V delta 1 sequences. Less abundant sequences were also detected repeatedly throughout the length of small intestine or colon. Moreover, the intestinal V delta 1 repertoire in the small intestine and colon appeared compartmentalized and showed no overlap with the V delta 1 repertoire in peripheral blood. Dominant V delta 1 transcripts in each subject differed between the small intestine and colon, and the dominant transcripts within these sites differed among individuals. Analysis of small intestinal transcripts obtained at a 1-yr interval revealed that the V delta 1 repertoire was stable over time. The fact that the majority of V delta 1 transcripts, both dominant and rare, are distributed throughout a several meter length of the adult intestinal tract and are stable over time suggests they are not generated by an ongoing process of in situ VDJ gene rearrangement. Our results favor a model in which the repertoire of V delta 1 T cells in the intestinal tract is shaped by positive selection in response to a limited array of ligands before the migration of V delta 1 cells throughout the small intestine or colon.

摘要

Vδ1 阳性 T 细胞构成了人类肠道中 γ/δ T 细胞的主要群体。为了深入了解这些细胞的产生机制及其受体库的多样性,我们对人类小肠和结肠中 Vδ1 T 细胞受体转录本的连接序列进行了特征分析。从小肠或结肠不同长度区域获取的黏膜活检组织中,高频出现一种或少数几种相同的符合读框的 Vδ1 序列。在小肠或结肠全长范围内也反复检测到丰度较低的序列。此外,小肠和结肠中的肠道 Vδ1 受体库似乎是分隔的,并且与外周血中的 Vδ1 受体库没有重叠。每个受试者小肠和结肠中的优势 Vδ1 转录本不同,而且这些部位内的优势转录本在个体之间也存在差异。对间隔 1 年获取的小肠转录本进行分析发现,Vδ1 受体库随时间推移是稳定的。大多数 Vδ1 转录本,无论是优势的还是罕见的,都分布在成年肠道数米长的范围内且随时间稳定,这一事实表明它们不是由正在进行的原位 VDJ 基因重排过程产生的。我们的结果支持这样一种模型,即肠道中 Vδ1 T 细胞的受体库是在 Vδ1 细胞迁移到整个小肠或结肠之前,通过对有限种类配体的阳性选择而形成的。

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