Dumont F J
J Immunol. 1987 Jun 15;138(12):4106-13.
Cross-linking of cell surface Ly-6C molecules with the 6C3 rat monoclonal antibody (MAb) followed by anti-rat immunoglobulin antibody acts in concert with phorbol myristate acetate (PMA) as a potent mitogenic stimulus for normal T cells. Specificity of this stimulation was demonstrated by its absence in T cells from NZB, NOD, or STb/J mice which lack the 6C3 determinant. In 6C3+ normal strains, the extent of 6C3-mediated stimulation varied, depending on the level of 6C3 antigen expression. Analysis of this stimulation in purified T cell subsets revealed that in Ly-6.1 strains (e.g., BALB/c, CBA/J), Lyt-2+ cells responded, but not L3T4+ cells, whereas in Ly-6.2 strains (e.g., C57BL/6, MRL-+/+), both subsets produced IL 2 and proliferated, although with different kinetics. Moreover, in adult MRL-+/+ mice, the minor Lyt-2-/L3T4- subset from the lymph nodes gave low responses to 6C3 cross-linking, whereas that from the thymus reacted strongly. Stimulation via Ly-6C therefore provides a pathway for differential activation of normal T cells. In contrast, the expanding population of Lyt-2-/L3T4- T cells from lpr/lpr or gld/gld mice did not proliferate in response to 6C3 antigen cross-linking plus PMA despite high levels of 6C3 antigen expression. Responsiveness of lpr/lpr T cells could not be restored with IL 1, IL 2, or both. These T cells also failed to be triggered by conjunction of PMA with either Thy-1 antigen cross-linking or concanavalin A. Moreover, they were not stimulated, in the presence of PMA, by doses of ionomycin that were optimal for normal T cells, but did respond to higher ionomycin concentrations (2 micrograms/ml), and this response was not altered by Ly-6C cross-linking. It is concluded that the Ly-6C pathway of T cell activation is not functional in the aberrant lpr/lpr (and gld/gld) T cells, and that this defect may reflect abnormalities of intracellular signaling.
用6C3大鼠单克隆抗体（MAb）使细胞表面Ly-6C分子交联，随后用抗大鼠免疫球蛋白抗体处理，可与佛波醇肉豆蔻酸酯乙酸酯（PMA）协同作用，作为正常T细胞的一种强效促有丝分裂刺激物。NZB、NOD或STb/J小鼠的T细胞缺乏6C3决定簇，不会出现这种刺激，从而证明了这种刺激的特异性。在6C3阳性的正常品系中，6C3介导的刺激程度有所不同，这取决于6C3抗原的表达水平。对纯化的T细胞亚群进行的这种刺激分析表明，在Ly-6.1品系（如BALB/c、CBA/J）中，Lyt-2+细胞有反应，而L3T4+细胞无反应；而在Ly-6.2品系（如C57BL/6、MRL-+/+）中，两个亚群都产生白细胞介素2并增殖，尽管动力学不同。此外，在成年MRL-+/+小鼠中，来自淋巴结的较小的Lyt-2-/L3T4-亚群对6C3交联反应较弱，而来自胸腺的该亚群反应强烈。因此，通过Ly-6C的刺激为正常T细胞的差异激活提供了一条途径。相比之下，来自lpr/lpr或gld/gld小鼠的不断扩增的Lyt-2-/L3T4- T细胞群体，尽管6C3抗原表达水平很高，但对6C3抗原交联加PMA无增殖反应。lpr/lpr T细胞的反应性不能用白细胞介素1、白细胞介素2或两者恢复。这些T细胞也不能被PMA与Thy-1抗原交联或伴刀豆球蛋白A联合触发。此外，在PMA存在的情况下，正常T细胞的最佳剂量离子霉素不能刺激它们，但它们对更高浓度的离子霉素（2微克/毫升）有反应，并且这种反应不会因Ly-6C交联而改变。得出的结论是，T细胞激活的Ly-6C途径在异常的lpr/lpr（和gld/gld）T细胞中不起作用，并且这种缺陷可能反映了细胞内信号传导的异常。
