Coles M C, Raulet D H
Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA 94720, USA.
J Immunol. 2000 Mar 1;164(5):2412-8. doi: 10.4049/jimmunol.164.5.2412.
NK1.1+ T cells represent a specialized T cell subset specific for CD1d, a nonclassical MHC class I-restricting element. They are believed to function as regulatory T cells. NK1.1+ T cell development depends on interactions with CD1d molecules presented by hematopoietic cells rather than thymic epithelial cells. NK1.1+ T cells are found in the thymus as well as in peripheral organs such as the liver, spleen, and bone marrow. The site of development of peripheral NK1.1+ T cells is controversial, as is the nature of the CD1d-expressing cell that selects them. With the use of nude mice, thymectomized mice reconstituted with fetal liver cells, and thymus-grafted mice, we provide direct evidence that NK1.1+ T cells in the liver are thymus dependent and can arise in the thymus from fetal liver precursor cells. We show that the class I+ (CD1d+) cell type necessary to select NK1.1+ T cells can originate from TCRalpha-/- precursors but not from TCRbeta-/- precursors, indicating that the selecting cell is a CD4+CD8+ thymocyte. 5-Bromo-2'-deoxyuridine-labeling experiments suggest that the thymic NK1.1+ T cell population arises from proliferating precursor cells, but is a mostly sessile population that turns over very slowly. Since liver NK1.1+ T cells incorporate 5-bromo-2'-deoxyuridine more rapidly than thymic NK1.1+ T cells, it appears that liver NK1.1+ T cells either represent a subset of thymic NK1.1+ T cells or are induced to proliferate after having left the thymus. The results indicate that NK1.1+ T cells, like conventional T cells, arise in the thymus where they are selected by interactions with restricting molecules.
NK1.1 + T细胞代表一类特定的T细胞亚群，对CD1d具有特异性，CD1d是一种非经典的MHC I类限制性元件。它们被认为具有调节性T细胞的功能。NK1.1 + T细胞的发育依赖于与造血细胞而非胸腺上皮细胞呈递的CD1d分子的相互作用。NK1.1 + T细胞存在于胸腺以及肝脏、脾脏和骨髓等外周器官中。外周NK1.1 + T细胞的发育位点存在争议，选择它们的表达CD1d的细胞的性质也存在争议。通过使用裸鼠、用胎肝细胞重建的胸腺切除小鼠以及胸腺移植小鼠，我们提供了直接证据，表明肝脏中的NK1.1 + T细胞依赖胸腺，并且可以在胸腺中由胎肝前体细胞产生。我们表明，选择NK1.1 + T细胞所必需的I类 +（CD1d +）细胞类型可源自TCRα - / - 前体细胞，但不能源自TCRβ - / - 前体细胞，这表明选择细胞是CD4 + CD8 + 胸腺细胞。5 - 溴 - 2'-脱氧尿苷标记实验表明，胸腺NK1.1 + T细胞群体源自增殖的前体细胞，但大多是静止群体，更新非常缓慢。由于肝脏NK1.1 + T细胞比胸腺NK1.1 + T细胞更快地掺入5 - 溴 - 2'-脱氧尿苷，看来肝脏NK1.1 + T细胞要么代表胸腺NK1.1 + T细胞的一个亚群，要么在离开胸腺后被诱导增殖。结果表明，NK1.1 + T细胞与传统T细胞一样，在胸腺中产生，在那里它们通过与限制性分子的相互作用被选择。
