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同种异体骨髓移植后长期免疫缺陷中携带γT细胞受体的循环CD3 +淋巴细胞的主要表达

Predominant expression of circulating CD3+ lymphocytes bearing gamma T cell receptor in a prolonged immunodeficiency after allogeneic bone marrow transplantation.

作者信息

Vilmer E, Guglielmi P, David V, Leca G, Rabian C, Degos L, Boiron M, Bensussan A

机构信息

Département d'Hématologie, Hôpital Saint Louis, Paris, France.

出版信息

J Clin Invest. 1988 Sep;82(3):755-61. doi: 10.1172/JCI113675.

Abstract

The cell surface expression of alpha:beta heterodimer was studied using WT31 monoclonal antibody, in peripheral blood lymphocytes (PBL) from a patient who developed a prolonged immunodeficiency after allogeneic bone marrow transplantation. This patient, grafted for chronic myelogenous leukemia, received T cell depleted bone marrow from her HLA, A, B, D matched sibling. The late occurrence of opportunistic infection, led us to analyze the phenotype of patient PBL. 70% of PBL were CD3+ and 29% WT31+, indicating that the majority of CD3+ PBL did not express the alpha:beta heterodimer. Transcription of the genes encoding the alpha, beta, and gamma chains was assessed in cell lines derived from PBL, by Northern blot analysis. We showed that the CD3+ WT31- subset expressed a truncated, beta mRNA (1.0 kb) and also truncated alpha transcript (1.4 kb). To determine the CD3-associated structure on CD3+ WT31- cell line, immunoprecipitation assays were performed using monoclonal anti-CD3 and an hetero antiserum against gamma peptides. These CD3+ WT31- cells expressed a disulfide linked dimer, composed of products of gamma gene (37 kD, 40 kD) and of undefined delta chain (45 kD). Functional analyses were performed in PBL before and after sorting with WT31 and anti-CD3 antibody. These circulating CD3+ WT31- cells were unable to proliferate when triggered with anti-T3 beads and they seemed to mediate a suppressor activity on CD3+ WT31+ cells.

摘要

使用WT31单克隆抗体研究了α:β异二聚体在细胞表面的表达,该研究对象是一位在异基因骨髓移植后出现长期免疫缺陷的患者的外周血淋巴细胞(PBL)。这位因慢性粒细胞白血病接受移植的患者,从与其HLA、A、B、D匹配的同胞那里接受了去除T细胞的骨髓。机会性感染的晚期发生促使我们分析患者PBL的表型。70%的PBL是CD3+,29%是WT31+,这表明大多数CD3+ PBL不表达α:β异二聚体。通过Northern印迹分析评估了源自PBL的细胞系中编码α、β和γ链的基因的转录情况。我们发现CD3+ WT31-亚群表达一种截短的β mRNA(1.0 kb)以及截短的α转录本(1.4 kb)。为了确定CD3+ WT31-细胞系上与CD3相关的结构,使用单克隆抗CD3抗体和针对γ肽的异源抗血清进行了免疫沉淀试验。这些CD3+ WT31-细胞表达一种由γ基因产物(37 kD、40 kD)和未明确的δ链(45 kD)组成的二硫键连接的二聚体。在用WT31和抗CD3抗体分选之前和之后,对PBL进行了功能分析。这些循环的CD3+ WT31-细胞在用抗T3珠刺激时无法增殖,并且它们似乎对CD3+ WT31+细胞介导一种抑制活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9aba/303579/90c8fddbbcba/jcinvest00081-0017-a.jpg

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