NEGATIVE REGULATION OF T-CELL ADHESION AND ACTIVATION BY CD43
NEGATIVE REGULATION OF T-CELL ADHESION AND ACTIVATION BY CD43
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DOI：
10.1038/377535a0
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发表时间：
1995-10-12
期刊：
影响因子：
64.8
通讯作者：
ARDMAN, B
中科院分区：
文献类型：
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作者：
MANJUNATH, N;CORREA, M;ARDMAN, B
CD 43是一种细胞表面唾液酸糖蛋白，由多种造血衍生细胞（包括T淋巴细胞）表达（1-9）。早期观察到X染色体连锁Wiskott-Aldrich综合征男孩的T淋巴细胞表达CD 43缺陷，提示CD 43在淋巴细胞功能中的重要性（10，11）。随后的研究表明，CD 43促进白细胞粘附（12-14），并在T细胞活化过程中具有共刺激作用（15）。为了确定CD 43的生理学相关功能，我们产生了CD 43敲除小鼠。我们在这里报告，CD 43缺陷的T细胞从这样的小鼠显示出显着增加，在他们的体外增殖反应伴刀豆球蛋白A，抗CD 3，超抗原SEB和同种异体刺激。此外，CD 43缺陷型T细胞在同型粘附和它们结合不同配体（包括纤连蛋白和细胞间粘附分子ICAM-1）的能力方面显示出显著增强。牛痘病毒感染的CD 43基因敲除小鼠与野生型同窝小鼠相比，其抗牛痘、细胞毒性T细胞应答增强，但病毒载量增加。我们的结论是，CD 43负调节T细胞活化和粘附，是重要的病毒清除。
CD43 is a cell-surface sialoglycoprotein expressed by a variety of haematopoietically derived cells, including T lymphocytes(1-9). Earlier observations of defective CD43 expression by T lymphocytes from boys with the X-chromosome-linked Wiskott-Aldrich syndrome suggested the importance of CD43 in lymphocyte function(10,11). Subsequent studies have suggested that CD43 facilitates leukocyte adhesion(12-14) and has a co-stimulatory role during T-cell activation(15). To define the physiologically relevant functions(s) of CD43, we have generated CD43-knockout mice. We report here that CD43-deficient T cells from such mice show a marked increase in their in vitro proliferative response to concanavalin A, anti-CD3, the superantigen SEB and allostimulation. Additionally, CD43-deficient T cells show a substantial enhancement in homotypic adhesion and in their ability to bind different ligands, including fibronectin and the intercellular adhesion molecule ICAM-1. Vaccinia-virus-infected CD43-knockout mice mounted an augmented anti-vaccinia, cytotoxic T-cell response compared with their wild-type littermates, yet developed an increased virus load. We conclude that CD43 negatively regulates T-cell activation and adhesion and is important for viral clearance.