Duprez V, Maziarz R, Weinberger O, Burakoff S J
J Immunol. 1984 May;132(5):2185-9.
A model system has been developed to study extrathymic T cell differentiation; mice have been thymectomized, lethally irradiated, and reconstituted with bone marrow cells depleted of Thy-1+ cells. After 8 wk, the spleen cells of these athymic, bone marrow-reconstituted chimeras contain Thy-1+ precytolytic T lymphocytes (CTL) that are able to respond to antigen only if supernatant from Con A-activated T cells is added to culture. The phenotype of these pre-CTL is similar to that of thymocytes, suggesting that they may be immature T cells. Initial evaluation of the CTL repertoire of these athymic mice demonstrated that the CTL generated to trinitrophenyl-modified syngeneic cells are H-2-restricted, and that the CTL generated to alloantigens have many of the cross-reactivities observed in normal mice but not in nude mice. In this report, we demonstrate a helper T cell defect in these thymectomized chimeras. These chimeras lack an Ly-1+ helper cell required for thymocytes to differentiate to CTL. Further studies revealed that when spleen cells from these thymectomized chimeras were stimulated with Con A, they produced normal levels of interleukin 2. However, these splenocytes were defective in the production of another factor needed for CTL differentiation.
已开发出一种模型系统来研究胸腺外T细胞分化；对小鼠进行胸腺切除、致死性照射，并用去除Thy-1+细胞的骨髓细胞进行重建。8周后，这些无胸腺、骨髓重建嵌合体的脾细胞含有Thy-1+前溶细胞性T淋巴细胞（CTL），只有在将伴刀豆球蛋白A激活的T细胞的上清液加入培养物中时，这些细胞才能对抗原作出反应。这些前CTL的表型与胸腺细胞相似，表明它们可能是未成熟的T细胞。对这些无胸腺小鼠的CTL库的初步评估表明，针对三硝基苯基修饰的同基因细胞产生的CTL受H-2限制，并且针对同种异体抗原产生的CTL具有许多在正常小鼠而非裸鼠中观察到的交叉反应性。在本报告中，我们证明了这些胸腺切除嵌合体存在辅助性T细胞缺陷。这些嵌合体缺乏胸腺细胞分化为CTL所需的Ly-1+辅助细胞。进一步的研究表明，当用伴刀豆球蛋白A刺激这些胸腺切除嵌合体的脾细胞时，它们产生正常水平的白细胞介素2。然而，这些脾细胞在产生CTL分化所需的另一种因子方面存在缺陷。
