CD4 AND CD45 REGULATE QUALITATIVELY DISTINCT PATTERNS OF CALCIUM MOBILIZATION IN INDIVIDUAL CD4(+) T-CELLS
CD4 AND CD45 REGULATE QUALITATIVELY DISTINCT PATTERNS OF CALCIUM MOBILIZATION IN INDIVIDUAL CD4(+) T-CELLS
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DOI：
10.1002/eji.1830250906
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发表时间：
1995-09-01
影响因子：
5.4
通讯作者：
BOTTOMLY, K
中科院分区：
文献类型：
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作者：
LEITENBERG, D;CONSTANT, S;BOTTOMLY, K
T细胞活化的早期结果是细胞内钙浓度的增加。视频激光显微镜技术的最新进展使得能够在刺激后随时间推移检查单个细胞。这些研究表明，细胞可以经历定性不同的钙动员模式，这表明不同的钙流模式可能与不同的信号通路，并可能差异影响细胞活化的晚期事件。在这份报告中，我们确定了CD4（+）T细胞中的不同模式的钙动员后，抗体介导的交联的CD3或CD4，或以下的交联的CD3和CD4的同时。这些作用可以通过CD45的交联进一步改变。我们发现，单独的CD3的抗体交联在加入交联抗体后不久在绝大多数细胞中诱导单个尖峰。相反，单独的CD4交联诱导重复钙尖峰的延迟模式，其与CD3交联相比振幅降低。CD3和CD4的同时交联诱导细胞内钙动员的持续增加，这取决于细胞外钙的存在。在T细胞与特异性抗原和抗原呈递细胞相互作用后，在CD3和CD4的生理交联后也观察到细胞内钙浓度的这种持续增加。最后，CD45、CD3和CD4的同时交联消除了在CD3和CD4交联后观察到的钙的持续增加。这些结果表明，T细胞受体信号传导的定性性质可以通过其他信号传导分子的分子缔合来调节，这些信号传导分子可以是T细胞受体复合物的一部分，也可以不是。
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, crosslinking CD4 alone induces a delayed pattern of repetitive calcium spikes which are decreased in amplitude compared to CD3 cross-linking. Simultaneous crosslinking 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.