Increased Zap-70 association with CD3ζ in CD4 T cells from old mice
Increased Zap-70 association with CD3ζ in CD4 T cells from old mice
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DOI：
10.1006/cimm.1998.1394
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发表时间：
1998-12-15
影响因子：
4.3
通讯作者：
Miller, RA
中科院分区：
文献类型：
--
作者：
Garcia, GG;Miller, RA
衰老使静息和活化小鼠CD 4 T细胞的CD 3 zeta链中磷酸酪氨酸的量减少约三倍，因此可以预期Zap-70与CD 3 zeta的结合以及CD 3 zeta复合物中Zap-70激酶功能相应下降。我们在这里显示，老化导致，出乎意料的是，在静止的CD 4 T细胞中与CD 3 zeta相关的Zap-70的量增加了大约两倍。然而，年龄对总细胞内Zap-70含量没有影响。将CD 3与CD 4交联导致来自年轻供体的新鲜分离的CD 4 T细胞的CD 3 zeta复合物中Zap-70的功能活性仅增加50%。与Jurkat和HT-2细胞相比，新鲜T细胞在CD 3 ζ复合物中显示出较高的Zap-70功能基线水平和较低的Zap-70功能诱导水平。来自老年小鼠的CD 4 T细胞具有与在来自年轻小鼠的活化T细胞中观察到的那些类似的Zap-70活性的基线水平，并且这些水平在CD 3/CD 4交联后不增加。Zap-70的酪氨酸特异性磷酸化在静止时在老年T细胞中也比在年轻T细胞中更高，并且仅在来自年轻供体的细胞中可诱导。这些数据表明，T细胞活化中与年龄相关的缺陷不太可能简单地归因于Zap-70与CD 3 zeta相关性的下降或Zap-70磷酸化的减少。尽管CD 3 zeta酪氨酸磷酸化随着年龄的增长而丧失，但CD 3 zeta-Zap相关性随着年龄的增长而增加，这表明来自年轻和老年供体的T细胞中CD 3 zeta ITAM组之间的酪氨酸磷酸基团的模式可能不同，或者在年轻的CD 4 T细胞中，进入CD 3 zeta内的ITAM区域可能被分子间或分子内空间位阻阻断。(C)北京：科学出版社.
Aging diminishes the amount of phosphotyrosine in the CD3 zeta chains of resting and activated mouse CD4 T cells by about threefold and might therefore be expected to a corresponding decline in Zap-70 association with CD3 zeta and in Zap-70 kinase function in CD3 zeta complexes. We show here that aging leads, unexpectedly, to an approximately twofold increase in the amount of Zap-70 associated with CD3 zeta in resting CD4 T cells. There is, however, no effect of age on total intracellular Zap-70 content. Cross-linking CD3 to CD4 leads to an increase of only 50% in the functional activity of Zap-70 in CD3 zeta complexes from freshly isolated CD4 T cells of young donors. Compared to Jurkat and HT-2 cells, fresh T cells show both higher baseline levels and lower induced levels of Zap-70 function in CD3 zeta complexes. CD4 T cells from old mice have baseline levels of Zap-70 activity similar to those seen in activated T cells from young mice, and these levels do not increase after CD3/CD4 cross-linking. Tyrosine-specific phosphorylation of Zap-70 is also higher at rest in old T cells than in young T cells and inducible only in cells from young donors. These data suggest that age-related defects in T cell activation are not likely to be attributable simply to a decline in Zap-70 association with CD3 zeta or to diminished Zap-70 phosphorylation. The increase with age in CD3 zeta-Zap association, despite the loss with age in CD3 zeta tyrosine phosphorylation, suggests that the pattern of tyrosine phosphate groups among CD3 zeta ITAM groups may be different in T cells from young and old donors or that access to ITAM regions within CD3 zeta may be blocked by inter- or intramolecular steric hindrance in young CD4 T cells. (C) 1998 Academic Press.