Tamura T, Kunimatsu T, Yee S T, Igarashi O, Utsuyama M, Tanaka S, Miyazaki S i, Hirokawa K, Nariuchi H
Department of Allergology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Int Immunol. 2000 Aug;12(8):1205-15. doi: 10.1093/intimm/12.8.1205.
It is well known that IL-2 production of CD4(+) T cells from old mice (old T cells) is impaired. In this study, we have examined TCR complex zeta chain expression of old T cells and their TCR downstream signal transduction pathways stimulated with anti-CD3. Activation of protein tyrosine kinases, Fyn and ZAP-70, and turnover of inositol phosphates stimulated with anti-CD3 were severely impaired in old T cells, although levels of these proteins were comparable to those in young T cells. Increase in intracellular Ca2+ concentration in old T cells was also impaired. Old T cells starting the Ca(2+) oscillation by the anti-CD3 stimulation were severely decreased in number and the oscillation waves were broader in shape. T cells with zeta-FcvarepsilonRgamma heterodimer in the TCR-CD3 complex were increased in proportion in old T cells with a concomitant decrease in the T cells with zeta-zeta homodimer. The density of the TCR-CD3 complex on old T cells was confirmed to be comparable to that on young T cells. The impairment in TCR downstream signal transduction pathways and the increase in zeta-FcvarepsilonRgamma heterodimer in the TCR-CD3 complex were confirmed to be the situation in Th1 clones established from old mice. These results indicate that old T cells are impaired in response to TCR stimulation, because T cells with the TCR-CD3 complex containing the zeta-FcvarepsilonRgamma heterodimer are increased in proportion in old T cells.
众所周知，老年小鼠的CD4(+) T细胞（老年T细胞）的白细胞介素-2产生受损。在本研究中，我们检测了老年T细胞的TCR复合物ζ链表达及其经抗CD3刺激后的TCR下游信号转导途径。尽管这些蛋白的水平与年轻T细胞中的相当，但老年T细胞中蛋白酪氨酸激酶Fyn和ZAP-70的激活以及抗CD3刺激后肌醇磷酸的周转严重受损。老年T细胞中细胞内Ca2+浓度的增加也受损。经抗CD3刺激引发Ca(2+)振荡的老年T细胞数量严重减少，且振荡波形状更宽。TCR-CD3复合物中具有ζ-FcεRγ异二聚体的T细胞在老年T细胞中的比例增加，同时具有ζ-ζ同二聚体的T细胞减少。老年T细胞上TCR-CD3复合物的密度经证实与年轻T细胞上的相当。TCR下游信号转导途径的受损以及TCR-CD3复合物中ζ-FcεRγ异二聚体的增加在从老年小鼠建立的Th1克隆中也得到证实。这些结果表明，老年T细胞对TCR刺激的反应受损，因为在老年T细胞中，含有ζ-FcεRγ异二聚体的TCR-CD3复合物的T细胞比例增加。
