Fibroblast dependency during early thymocyte development maps to the CD25(+) CD44(+) stage and involves interactions with fibroblast matrix molecules
Fibroblast dependency during early thymocyte development maps to the CD25(+) CD44(+) stage and involves interactions with fibroblast matrix molecules
复制标题
DOI：
10.1002/eji.1830270522
复制
发表时间：
1997-03-01
影响因子：
5.4
通讯作者：
Jenkinson, EJ
中科院分区：
文献类型：
--
作者：
Anderson, G;Anderson, KL;Jenkinson, EJ
我们通过分离和重新聚集单个或组合基质细胞的前体亚群，研究了胸腺基质的特定成分在CD 4（-）8（-）T细胞前体发育过程中的作用。我们发现，虽然CD 25（+）44（+）前体细胞的发育依赖于主要组织相容性复合体（MHC）II类+胸腺上皮细胞和成纤维细胞的组合，但它们的直系后代CD 25（+）44（-）前体细胞在单独存在MHC II类+胸腺上皮细胞的情况下发育到CD 4（+）8（+）阶段。因此，CD 25（+）44（+）前体是依赖成纤维细胞支持的最后发育阶段。此外，虽然代谢不活跃，但1-乙基-3-（3 '-二甲基氨基丙基）碳二亚胺（ECDI）处理的成纤维细胞保留了促进T细胞发育的能力，而之前用透明质酸酶处理消除了这种作用，表明成纤维细胞相关的细胞外基质组分是所涉及的关键因素。在支持这一点，我们表明，成纤维细胞位于皮质区的胸腺T细胞前体是已知的居住，这些成纤维细胞与广泛的细胞外基质上没有发现胸腺上皮细胞。最后，α 4整联蛋白和CD 44的抗体干扰了在再聚集培养物中由CD 25（+）44（+）前体产生CD 4（+）8（+）细胞的效率，并且还降低了后者与3 T3成纤维细胞的结合，这表明这些分子在使T细胞前体与成纤维细胞相关的细胞外基质接触中起作用。
We have investigated the role of specific components of the thymic stroma during development of CD4(-)8(-) T cell precursors by separating and reaggregating precursor subsets with individual or combinations of stromal cells. We show that while the development of CD25(+) 44(+) precursors is dependent upon a combination of major histocompatibility complex (MHC) class II+ thymic epithelial cells and fibroblasts, their direct descendants, CD25(+) 44(-) precursors, develop to the CD4(+) 8(+) stage in the presence of MHC class II+ thymic epithelial cells alone. Thus, CD25(+) 44(+) precursors are the last developmental stage to be dependent upon fibroblast support. In addition, while metabolically inactive, 1-ethyl-3-(3'-dimethylaminopropyl)carbodiimide (ECDI)-treated fibroblasts retain the ability to promote T cell development, prior treatment with hyaluronidase abrogates this effect, suggesting that fibroblast-associated extracellular matrix components are the key elements involved. In support of this, we show that fibroblasts are located in cortical regions of the thymus where T cell precursors are known to reside, and that these fibroblasts are associated with an extensive extracellular matrix not found on thymic epithelial cells. Finally, antibodies to alpha 4 integrin and CD44 interfere with the efficiency with which CD4(+) 8(+) cells are generated from CD25(+) 44(+) precursors in reaggregate cultures and also reduce the binding of the latter to 3T3 fibroblasts, suggesting these molecules play a role in bringing T cell precursors into contact with fibroblast-associated extracellular matrix.