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TCRζ链双阳性淋巴细胞定义了迁移至炎症组织的循环效应细胞群体。

TCRzetadim lymphocytes define populations of circulating effector cells that migrate to inflamed tissues.

作者信息

Zhang Zhuoli, Gorman Claire L, Vermi Anna-Chiara, Monaco Claudia, Foey Andrew, Owen Sally, Amjadi Parisa, Vallance Alena, McClinton Catherine, Marelli-Berg Federica, Isomäki Pia, Russell Andrew, Dazzi Francesco, Vyse Timothy J, Brennan Fionula M, Cope Andrew P

机构信息

Kennedy Institute of Rheumatology Division, Faculty of Medicine, Imperial College, Hammersmith, London, United Kingdom.

出版信息

Blood. 2007 May 15;109(10):4328-35. doi: 10.1182/blood-2006-12-064170. Epub 2007 Jan 25.

DOI:10.1182/blood-2006-12-064170
PMID:17255353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1939810/
Abstract

The T-cell receptor zeta (TCRzeta) chain is a master sensor and regulator of lymphocyte responses. Loss of TCRzeta expression has been documented in infectious, inflammatory, and malignant diseases, suggesting that it may serve to limit T-cell reactivity and effector responses at sites of tissue damage. These observations prompted us to explore the relationship between TCRzeta expression and effector function in T cells. We report here that TCRzeta(dim) lymphocytes are enriched for antigen-experienced cells refractory to TCR-induced proliferation. Compared to their TCRzeta(bright) counterparts, TCRzeta(dim) cells share characteristics of differentiated effector T cells but use accessory pathways for transducing signals for inflammatory cytokine gene expression and cell contact-dependent pathways to activate monocytes. TCRzeta(dim) T cells accumulate in inflamed tissues in vivo and have intrinsic migratory activity in vitro. Whilst blocking leukocyte trafficking with anti-TNF therapy in vivo is associated with the accumulation of TCRzeta(dim) T cells in peripheral blood, this T-cell subset retains the capacity to migrate in vitro. Taken together, the functional properties of TCRzeta(dim) T cells make them promising cellular targets for the treatment of chronic inflammatory disease.

摘要

T细胞受体ζ（TCRζ）链是淋巴细胞反应的主要传感器和调节器。在感染性、炎症性和恶性疾病中已记录到TCRζ表达缺失，这表明它可能在组织损伤部位限制T细胞反应性和效应反应。这些观察结果促使我们探索TCRζ表达与T细胞效应功能之间的关系。我们在此报告，TCRζ低表达淋巴细胞富含对TCR诱导增殖具有抗性的抗原经历细胞。与TCRζ高表达的对应细胞相比，TCRζ低表达细胞具有分化效应T细胞的特征，但利用辅助途径转导炎症细胞因子基因表达信号，并通过细胞接触依赖途径激活单核细胞。TCRζ低表达T细胞在体内炎症组织中积聚，在体外具有内在迁移活性。虽然体内用抗TNF疗法阻断白细胞运输与外周血中TCRζ低表达T细胞的积聚有关，但该T细胞亚群在体外仍保留迁移能力。综上所述，TCRζ低表达T细胞的功能特性使其成为治疗慢性炎症性疾病的有前景的细胞靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/9767b26e69e1/zh80100701060007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/945be7370300/zh80100701060001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/f46ebe3c0881/zh80100701060002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/b3e2dbf7deb3/zh80100701060003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/f082c9bf856c/zh80100701060004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/34f4810c00e8/zh80100701060005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/2a238494acb6/zh80100701060006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/9767b26e69e1/zh80100701060007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/945be7370300/zh80100701060001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/f46ebe3c0881/zh80100701060002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/b3e2dbf7deb3/zh80100701060003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/f082c9bf856c/zh80100701060004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/34f4810c00e8/zh80100701060005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/2a238494acb6/zh80100701060006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28ef/1939810/9767b26e69e1/zh80100701060007.jpg

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