Nickas G, Meyers J, Hebshi L D, Ashwell J D, Gold D P, Sydora B, Ucker D S
Division of Immunology, Medical Biology Institute, La Jolla, California 92037.
Mol Cell Biol. 1992 Jan;12(1):379-85. doi: 10.1128/mcb.12.1.379-385.1992.
The failure of Thy-1 and Ly-6 to trigger interleukin-2 production in the absence of surface T-cell antigen receptor complex (TCR) expression has been interpreted to suggest that functional signalling via these phosphatidylinositol-linked alternative activation molecules is dependent on the TCR. We find, in contrast, that stimulation of T cells via Thy-1 or Ly-6 in the absence of TCR expression does trigger a biological response, the cell suicide process of activation-driven cell death. Activation-driven cell death is a process of physiological cell death that likely represents the mechanism of negative selection of T cells. The absence of the TCR further reveals that signalling leading to activation-driven cell death and to lymphokine production are distinct and dissociable. In turn, the ability of alternative activation molecules to function in the absence of the TCR raises another issue: why immature T cells, thymomas, and hybrids fail to undergo activation-driven cell death in response to stimulation via Thy-1 and Ly-6. One possibility is that these activation molecules on immature T cells are defective. Alternatively, susceptibility to activation-driven cell death may be developmentally regulated by TCR-independent factors. We have explored these possibilities with somatic cell hybrids between mature and immature T cells, in which Thy-1 and Ly-6 are contributed exclusively by the immature partner. The hybrid cells exhibit sensitivity to activation-driven cell death triggered via Thy-1 and Ly-6. Thus, the Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 molecules of the immature T cells can function in a permissive environment. Moreover, with regard to susceptibility to Thy-1 and Ly-6 triggering, the mature phenotype of sensitivity to cell death is genetically dominant.
在缺乏表面T细胞抗原受体复合物（TCR）表达的情况下，Thy-1和Ly-6无法触发白细胞介素-2的产生，这被解释为表明通过这些磷脂酰肌醇连接的替代激活分子的功能信号传导依赖于TCR。相比之下，我们发现，在缺乏TCR表达的情况下，通过Thy-1或Ly-6刺激T细胞确实会触发一种生物学反应，即激活驱动的细胞死亡这一细胞自杀过程。激活驱动的细胞死亡是一种生理性细胞死亡过程，可能代表了T细胞阴性选择的机制。TCR的缺失进一步揭示，导致激活驱动的细胞死亡和淋巴因子产生的信号传导是不同的且可分离的。反过来，替代激活分子在缺乏TCR时发挥功能的能力引发了另一个问题：为什么未成熟T细胞、胸腺瘤和杂交细胞在通过Thy-1和Ly-6受到刺激时不能经历激活驱动的细胞死亡。一种可能性是未成熟T细胞上的这些激活分子存在缺陷。或者，对激活驱动的细胞死亡的易感性可能受TCR非依赖性因素的发育调控。我们用成熟和未成熟T细胞之间的体细胞杂交体探索了这些可能性，其中Thy-1和Ly-6完全由未成熟的亲本提供。杂交细胞对通过Thy-1和Ly-6触发的激活驱动的细胞死亡表现出敏感性。因此，未成熟T细胞的Thy-1和Ly-6分子可以在允许的环境中发挥作用。此外，关于对Thy-1和Ly-6触发的易感性，对细胞死亡敏感的成熟表型在遗传上是显性的。
