Weiss A, Dazin P F, Shields R, Fu S M, Lanier L L
Department of Medicine, Howard Hughes Medical Institute, University of California, San Francisco 94143.
J Immunol. 1987 Nov 15;139(10):3245-50.
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.
T细胞抗原受体可能在胸腺的阳性和阴性选择中都发挥作用。胸腺细胞的三个群体可通过T细胞抗原受体（CD3/Tiα/β）复合物的CD3-α/β链异二聚体的表达水平来区分。未能表达这些受体或表达低水平受体的细胞包含在一群表达低水平CD5抗原且主要为CD4+/CD8+的胸腺细胞中。因此，这些细胞在表型上似乎相对不成熟。相反，高表达CD3/Tiα/β的细胞共表达高水平的CD5，并且主要包含在表达CD4或CD8的更成熟的单阳性细胞中。利用钙敏感染料Indo-1和免疫荧光技术，我们证明，尽管表达低水平CD3/Tiα/β的细胞在表型上相对不成熟，但当用CD3单克隆抗体刺激时，这些抗原受体能够介导跨膜信号传导。尽管在这些低表达CD3/Tiα/β的细胞中观察到钙的增加是对抗CD3的反应，但即使在存在佛波酯肉豆蔻酸酯的情况下也未观察到增殖反应。在高表达CD3/Tiα/β的更成熟细胞中观察到了增殖反应。这些结果表明，抗原受体复合物介导跨膜信号传导事件的功能能力并非存在缺陷，而是胸腺细胞发育的不同阶段对抗原受体产生的信号的细胞反应可能有所不同。
