Leitenberg D, Constant S, Lu D D, Smith B R, Bottomly K
Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520-8011, USA.
Eur J Immunol. 1995 Sep;25(9):2445-51. doi: 10.1002/eji.1830250906.
An early consequence of T cell activation is an increase in intracellular calcium concentration. Recent advances in video laser microscopic techniques enable the examination of individual cells over time following stimulation. Such studies have revealed that cells can undergo qualitatively distinct patterns of calcium mobilization, suggesting that different patterns of calcium flux may be associated with different signaling pathways and may differentially affect late events in cell activation. In this report, we identify distinct patterns of calcium mobilization in CD4+ T cells following the antibody-mediated cross-linking of either CD3 or CD4, or following the cross-linking of both CD3 and CD4 simultaneously. These effects can be further modified by the cross-linking of CD45. We find that antibody cross-linking of CD3 alone induces a single spike in the vast majority of cells shortly after the addition of the cross-linking antibody. In contrast, cross-linking CD4 alone induces a delayed pattern of repetitive calcium spikes which are decreased in amplitude compared to CD3 cross-linking. Simultaneous cross-linking of CD3 and CD4 induces a sustained increase in intracellular calcium mobilization which is dependent on the presence of extracellular calcium. This sustained increase in intracellular calcium concentration is also seen following physiologic cross-linking of CD3 and CD4 after T cell interaction with specific antigen and antigen-presenting cells. Finally, the simultaneous cross-linking of CD45, CD3 and CD4 abrogates the sustained increase in calcium seen following CD3 and CD4 cross-linking. These results suggest that the qualitative nature of T cell receptor signaling can be modulated by the molecular association of other signaling molecules, which may be part of the T cell receptor complex or not.
T细胞活化的早期结果是细胞内钙浓度升高。视频激光显微技术的最新进展使得能够在刺激后随时间检查单个细胞。此类研究表明，细胞可经历性质不同的钙动员模式，这表明不同的钙流模式可能与不同的信号通路相关，并可能对细胞活化后期事件产生不同影响。在本报告中，我们确定了在抗体介导的CD3或CD4交联后，或在CD3和CD4同时交联后，CD4+T细胞中不同的钙动员模式。这些效应可通过CD45的交联进一步改变。我们发现，单独抗体交联CD3在添加交联抗体后不久，绝大多数细胞中会诱导出单个峰值。相比之下，单独交联CD4会诱导出延迟的重复性钙峰值模式，与CD3交联相比，其幅度降低。CD3和CD4同时交联会诱导细胞内钙动员持续增加，这依赖于细胞外钙的存在。在T细胞与特异性抗原和抗原呈递细胞相互作用后，CD3和CD4发生生理性交联时，也会出现细胞内钙浓度的这种持续增加。最后，CD45、CD3和CD4同时交联会消除CD3和CD4交联后出现的钙持续增加。这些结果表明，T细胞受体信号传导的性质可被其他信号分子的分子缔合所调节，这些信号分子可能是或不是T细胞受体复合物的一部分。
