Functional competency of T cell antigen receptors in human thymus.

Functional competency of T cell antigen receptors in human thymus.
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DOI:
10.4049/jimmunol.139.10.3245
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发表时间:
1987-11
影响因子:
4.4
通讯作者:
A. Weiss;P. Dazin;R. Shields;S. Fu;L. Lanier
A. Weiss;P. Dazin;R. Shields;S. Fu;L. Lanier
中科院分区:
医学2区
文献类型:
--
作者:
A. Weiss;P. Dazin;R. Shields;S. Fu;L. Lanier

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T 细胞抗原受体可能在胸腺的正选择和负选择中发挥作用。胸腺细胞的三个群体可以通过 T 细胞抗原受体 (CD3/Ti α/β) 复合物的 CD3-α/β 链异二聚体的表达水平来区分。不能表达这些受体或表达低水平受体的细胞包含在表达低水平CD5抗原并且主要是CD4+/CD8+的胸腺细胞群中。因此,这些细胞在表型上似乎相对不成熟。相反,表达高水平CD3/Tiα/β的细胞共表达高水平CD5并且主要包含在表达CD4或CD8的更成熟的单阳性细胞中。通过钙敏感染料 Indo-1 和免疫荧光,我们证明,尽管表达低水平 CD3/Ti α/β 的细胞相对表型不成熟,但这些抗原受体在受到 CD3 单克隆抗体刺激时能够介导跨膜信号传导。尽管在这些 CD3/Ti α/β 低表达细胞中观察到响应抗 CD3 后钙含量增加,但即使在存在佛波醇肉豆蔻酸酯乙酸酯的情况下,也没有观察到增殖反应。在表达高水平 CD3/Ti α/β 的更成熟细胞中观察到增殖反应。这些结果表明,细胞对抗原受体产生的信号的反应在胸腺细胞发育的不同阶段可能不同,而不是抗原受体复合物介导跨膜信号传导事件的功能能力缺陷。
The T cell antigen receptor is likely to play a role in both positive and negative selection in the thymus. Three populations of thymocytes can be distinguished by the level of expression of the CD3-alpha/beta-chain heterodimer of the T cell antigen receptor (CD3/Ti alpha/beta) complex. Cells which fail to express these receptors or express low levels of receptors are contained in a population of thymocytes which express low levels of the CD5 antigen and are predominantly CD4+/CD8+. Thus, these cells appear to be relatively immature phenotypically. In contrast, the cells which express high levels of CD3/Ti alpha/beta co-express high levels of CD5 and are predominantly contained in the more mature single positive cells which express either CD4 or CD8. With the calcium-sensitive dye, Indo-1, and immunofluorescence, we demonstrated that, despite the relative phenotypic immaturity of cells which express low levels of CD3/Ti alpha/beta, these antigen receptors are able to mediate transmembrane signaling when stimulated with CD3 monoclonal antibodies. Although increases in calcium were observed in these CD3/Ti alpha/beta-low expressing cells in response to anti-CD3, no proliferative response was observed, even in the presence of phorbol myristate acetate. Proliferative responses were observed in the more mature cells which express high levels of CD3/Ti alpha/beta. These results suggest that, rather than a defect in the functional capability of the antigen receptor complex to mediate transmembrane signaling events, cellular responses to signals generated by the antigen receptor may differ at various stages of thymocyte development.