Human invariant Vαa24-JαQ TCR supports the development of CD1d-dependent NK1.1+ and NK1.1- T cells in transgenic mice
Human invariant Vαa24-JαQ TCR supports the development of CD1d-dependent NK1.1+ and NK1.1- T cells in transgenic mice
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DOI：
10.4049/jimmunol.170.5.2390
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发表时间：
2003-03-01
影响因子：
4.4
通讯作者：
Casorati, G
中科院分区：
文献类型：
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作者：
Capone, M;Cantarella, D;Casorati, G
相当一部分表达NK细胞标记物NK1.1 （NKT细胞）的T细胞具有非常保守的TCR，其特征是同源不变（inv.） TCR Valpha24-JalphaQ和Valpha14-Jalpha18，分别在人和小鼠中重排，因此被定义为inv. NKT细胞。由于人类inv. NKT细胞在体外可以识别小鼠CD1d，我们想知道人类inv. Valpha24 TCR是否可以通过CD1d呈现的小鼠配体在体内选择，从而支持小鼠inv. NKT细胞的发育。因此，我们在所有T细胞中产生了表达人invv . Valpha24-JalphaQ TCR链的转基因（Tg）小鼠。人类inv. V24 TCR在TCR Calpha（-/-）小鼠中的表达确实挽救了inv. NKT细胞的发育，inv. NKT细胞优先回到肝脏并对cd1 -限制性配体α -半乳糖神经酰胺（α - galcer）有反应。然而，与来自非Tg小鼠的inv. NKT细胞不同，Valpha24 Tg小鼠的大部分NKT细胞表现为双阴性表型，TCR Vbeta7的使用显著增加，TCR Vbeta8.2的使用相应减少。尽管在Calpha（-/-）小鼠中强制表达人cd1d限制性TCR，但用mcd1d - α - galcer四聚体染色显示外周cd1d依赖性T淋巴细胞的绝对数量最多增加2倍。这种增加主要是由于结合cd1 - α - galcer四聚体的NK1.1(-) T细胞的比例增加。这些发现表明，人inv. Valpha24 TCR支持小鼠cd1依赖性淋巴细胞的发育，并支持对inv. NKT细胞总数的严格稳态控制。因此，表达人类inv. Valpha24 tcr的小鼠是研究inv. NKT细胞亚群不同方面的一个有价值的模型。
A sizable fraction of T cells expressing the NK cell marker NK1.1 (NKT cells) bear a very conserved TCR, characterized by homologous invariant (inv.) TCR Valpha24-JalphaQ and Valpha14-Jalpha18, rearrangements in humans and mice, respectively, and are thus defined as inv. NKT cells. Because human inv. NKT cells recognize mouse CD1d in vitro, we wondered whether a human inv. Valpha24 TCR could be selected in vivo by mouse ligands presented by CD1d, thereby supporting the development of inv. NKT cells in mice. Therefore, we generated transgenic (Tg) mice expressing the human inv. Valpha24-JalphaQ TCR chain in all T cells. The expression of the human inv. V24 TCR in TCR Calpha(-/-) mice indeed rescues the development of inv. NKT cells, which home preferentially to the liver and respond to the CD1d-restricted ligand a-galactosylceramide (alpha-GalCer). However, unlike inv. NKT cells from non-Tg mice, the majority of NKT cells in Valpha24 Tg mice display a double-negative phenotype, as well as a significant increase in TCR Vbeta7 and a corresponding decrease in TCR Vbeta8.2 use. Despite the forced expression of the human CD1d-restricted TCR in Calpha(-/-) mice, staining with mCD1d-alpha-GalCer tetramers reveals that the absolute numbers of peripheral CD1d-dependent T lymphocytes increase at most by 2-fold. This increase is accounted for mainly by an increased fraction of NK1.1(-) T cells that bind CD1d-alpha-GalCer tetramers. These findings indicate that human inv. Valpha24 TCR supports the development of CD1d-dependent lymphocytes in mice, and argue for a tight homeostatic control on the total number of inv. NKT cells. Thus, human inv. Valpha24 TCR-expressing mice are a. valuable model to study different aspects of the inv. NKT cell subset.