Restricted expression of transgenic HLA‐DRA gene in thymic epithelial cells and its role in acquisition of T cell tolerance to self‐superantigens and processed DRα‐derived peptide

Restricted expression of transgenic HLA‐DRA gene in thymic epithelial cells and its role in acquisition of T cell tolerance to self‐superantigens and processed DRα‐derived peptide
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转基因HLA-DRA基因在胸腺上皮细胞中的限制性表达及其在获得T细胞对自身超抗原和加工的DRα衍生肽的耐受中的作用

DOI:
10.1002/eji.1830230742
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发表时间:
1993
影响因子:
5.4
通讯作者:
T. Sasazuki
T. Sasazuki
中科院分区:
医学3区
文献类型:
--
作者:
Y. Fukui;Ken Yamamoto;Nobuhiko Yokoyama;T. Iwanaga;C. Kurashima;Y. Esaki;A. Kimura;T. Akashi;K. Hirokawa;T. Sasazuki

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我们已经建立了一组转基因小鼠系,其中HLA-B1基因在不同的细胞类型中表达。在一个细胞系(DRα-24)中,DRαEβB分子在胸腺髓质和皮质上皮细胞以及除胸腺巨噬细胞外的所有骨髓源性抗原呈递细胞(APC)谱系上表达。相比之下,另一个细胞系(DRα-30)中的分子表达见于胸腺髓质和皮质上皮细胞,但未见于胸腺和外周的骨髓源性APC。为了评价胸腺上皮细胞在获得T细胞耐受中的作用,进行了DRα-24和DRα-30的比较分析。在DRα-30中,表达TcR Vβ5和Vβ11的T细胞被消除至与DRα-24中相当的水平,表明胸腺上皮细胞上DRαEβB分子的表达足以克隆性删除自身超抗原反应性T细胞。此外,即使在存在外源性白细胞介素-2的情况下,来自DR α-30以及来自DR α-24的CD 4 + T细胞对来自DRα-24的脾细胞上表达的DRα衍生肽/I-Ab复合物也具有耐受性。这些观察结果表明,胸腺上皮细胞中DRα链的表达可能通过自身反应性T细胞的克隆缺失诱导针对与I-Ab分子结合的天然加工DRα衍生肽的T细胞耐受。
We have established a set of transgenic mouse lines in which the HLA‐DRA gene was expressed in different cell types. In one line (DRα‐24), DRαEβb molecules were expressed on thymic medullary and cortical epithelial cells and all lineages of bone marrow‐derived antigen‐presenting cells (APC) except for thymic macrophages. By contrast, expression of the molecules in another line (DRα‐30) was found on thymic medullary and cortical epithelial cells but not on bone marrow‐derived APC in the thymus and periphery. To evaluate the role of thymic epithelial cells in acquisition of T cell tolerance, comparative analysis of DRα‐24 and DRα‐30 was performed. In DRα‐30, T cells expressing TcR Vβ5 and Vβ11 were eliminated to comparable levels to those in DRα‐24, suggesting that expression of the DRαEβb molecules on thymic epithelial cells are sufficient for clonal deletion of the self‐superantigen‐reactive T cells. In addition, CD4+ T cells from DRa‐30 as well as those from DRα‐24 were tolerant to DRα‐derived peptide/I‐Ab complex expressed on spleen cells from DRα‐24 even in the presence of exogenous interleukin‐2. These observations suggest that expression of the DRα chain in thymic epithelial cells could induce T cell tolerance directed toward naturally processed DRα‐derived peptide bound to I‐Ab molecules, probably via clonal deletion of the self‐reactive T cells.
胸腺抗辐射成分上表达的 H-2 产品诱导的自身反应性 V beta 6 T 细胞的克隆消除。
DOI: 10.1093/intimm/4.1.75
发表时间: 1992
影响因子: 4.4
作者:
Arase,H;Arase,N;Ogasawara,K;Good,RA;Onoè,K
通讯作者: Onoè,K
一种可区分 T 细胞和 B 细胞亚群的单克隆抗体。
DOI: --
发表时间: 1981
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Bruce,J;Symington,FW;McKearn,TJ;Sprent,J
通讯作者: Sprent,J