Differentiation of thymocytes from CD3-CD4-CD8- through CD3-CD4-CD8+ into more mature stages induced by a thymic stromal cell clone.

Differentiation of thymocytes from CD3-CD4-CD8- through CD3-CD4-CD8+ into more mature stages induced by a thymic stromal cell clone.
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胸腺基质细胞克隆诱导胸腺细胞从 CD3-CD4-CD8- 到 CD3-CD4-CD8 分化为更成熟的阶段。

DOI:
10.1073/pnas.87.7.2750
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发表时间:
1990
影响因子:
11.1
通讯作者:
T. Hamaoka
T. Hamaoka
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Y. Tatsumi;A. Kumanogoh;M. Saitoh;Y. Mizushima;K. Kimura;S. Suzuki;H. Yagi;A. Horiuchi;M. Ogata;T. Hamaoka

文献摘要

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我们研究了我们建立的胸腺基质细胞克隆(MRL104.8a)或其衍生因子诱导未成熟胸腺细胞分化的能力。将纯化的成年鼠双阴性(CD4-CD8-,此处表示为 CD4-8-)胸腺细胞在 MRL104.8a 胸腺基质细胞单层上培养 1 天,导致诱导相当比例的 CD4-8+ 胸腺细胞。骨髓来源的基质细胞单层或 L929 成纤维细胞单层未能产生 CD4-8+ 细胞。这种分化也可以通过 MRL104.8a 培养上清液的半纯化样品诱导,该样品含有胸腺基质衍生的 T 细胞生长因子,能够促进双阴性未成熟胸腺细胞的生长。与 MRL104.8a 细胞或含有胸腺基质来源的 T 细胞生长因子的样品共培养 1 天后产生的 CD4-8+ 胸腺细胞被发现为 CD3- 和 J11d+,排除胸腺中存在的成熟 (CD3+4-8+) 胸腺细胞扩增的可能性。更重要的是,当培养时间延长至2或3天时,MRL104.8a单层上产生了相当数量的CD4+8+和单阳性(CD4+)细胞。因此,这些结果直接证明了 CD3-4-8- 未成熟胸腺细胞通过快速循环中间体 (CD3-4-8+) 被特殊的胸腺基质成分促进分化为双阳性和单阳性细胞。
We have investigated the capacity of our established thymic stromal cell clone (MRL104.8a) or its derived factor(s) to induce the differentiation of immature thymocytes. Culture of purified adult murine double-negative (CD4-CD8-, indicated here as CD4-8-) thymocytes on the MRL104.8a thymic stromal cell monolayer for 1 day resulted in the induction of an appreciable percentage of CD4-8+ thymocytes. A bone marrow-derived stromal cell monolayer or a L929 fibroblast monolayer failed to generate CD4-8+ cells. This differentiation could also be induced by a semipurified sample of the MRL104.8a culture supernatant, which contained a thymic stroma-derived T-cell growth factor capable of contributing to the growth of double-negative immature thymocytes. CD4-8+ thymocytes generated 1 day after coculture with the MRL104.8a cells or the sample containing thymic stroma-derived T-cell growth factor were found to be CD3- and J11d+, excluding the possibility of expansion of mature (CD3+4-8+) thymocytes present in the thymus. More importantly, when the culture period was extended to 2 or 3 days, an appreciable number of CD4+8+ and single-positive (CD4+) cells were generated on the MRL104.8a monolayer. Thus, these results provide the direct demonstration that CD3-4-8- immature thymocytes are promoted to differentiate through a rapidly cycling intermediate (CD3-4-8+) into double- and single-positive cells by a specialized thymic stromal component.