Intracellular calcium signalling patterns reflect the differentiation status of human T cells
Intracellular calcium signalling patterns reflect the differentiation status of human T cells
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DOI：
10.1111/j.1365-2249.2008.03677.x
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发表时间：
2008-07-01
影响因子：
4.6
通讯作者：
Young, S. P.
中科院分区：
文献类型：
--
作者：
Arrol, H. P.;Church, L. D.;Young, S. P.
T淋巴细胞的刺激导致大量基因的钙依赖性激活和抑制。然而，不同T细胞亚群的功能反应是异质的，因为它们的分化导致它们对活化的敏感性和细胞因子分泌的改变。在这里，我们研究了CD4和CD8 T细胞亚群中钙反应的模式，以帮助解释它们对活化的不同反应。从人血液中新鲜分离的CD 4（+）CD 45 RA（+）T细胞在刺激后发出持续的钙信号，但这比CD 4（+）CD 45 RO（+）细胞中引发的信号要小。在CD4（+）CD45RA（+）细胞体外分化为CD45RO（+）时，胞浆钙反应水平最初升高，但随后在进一步的分化过程中稳定下降。产生振荡钙响应或不响应的比例增加，分化伴随着细胞内池之间的钙的变化。CD8（+）T细胞比配对的CD4（+）T细胞产生更小的钙反应，并且显示出产生瞬时而不是持续钙信号的细胞数量的差异。CD4（+）CD45RO（+）群体中振荡细胞的增加可能反映了该群体的异质性，特别是在细胞因子产生方面。随着T细胞分化，T细胞中钙反应的变化模式可以解释细胞在其寿命的不同阶段对激活的反应的变化，并强调钙信号的数量和质量在确定T细胞激活结果中的重要性。
Stimulation of T lymphocytes results in the calcium-dependent activation and repression of a large number of genes. However, the functional response made by different T cell subsets is heterogeneous, as their differentiation results in alterations in their sensitivity to activation and in the secretion of cytokines. Here we have investigated the patterns of calcium responses in CD4 and CD8 T cell subsets to help explain their different responses to activation. CD4(+) CD45RA(+) T cells isolated freshly from human blood gave a sustained calcium signal after stimulation, but this was smaller than elicited in CD4(+) CD45RO(+) cells. On in vitro differentiation of CD4(+) CD45RA(+) cells to CD45RO(+), the level of the cytoplasmic calcium response rose initially, but then declined steadily during further rounds of differentiation. The proportion producing an oscillatory calcium response or not responding was increased and differentiation was accompanied by a shift in the calcium between intracellular pools. CD8(+) T cells gave a smaller calcium response than paired CD4(+) T cells and showed a difference in the numbers of cells giving a transient, rather than sustained, calcium signal. The increase in oscillating cells in the CD4(+) CD45RO(+) population may reflect the heterogeneity of this population, particularly in terms of cytokine production. The changing patterns of calcium responses in T cells as they differentiate may explain variation in the cellular response to activation at different stages in their lifespan and emphasize the importance of the both the quantity and the quality of the calcium signal in determining the outcome of T cell activation.