Cutting edge:: T lymphocyte activation by repeated immunological synapse formation and intermittent signaling

Cutting edge:: T lymphocyte activation by repeated immunological synapse formation and intermittent signaling
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DOI:
10.4049/jimmunol.171.3.1128
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发表时间:
2003-08-01
影响因子:
4.4
通讯作者:
Valitutti, S
Valitutti, S
中科院分区:
医学2区
文献类型:
--
作者:
Faroudi, M;Zaru, R;Valitutti, S

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生物性T细胞应答的激活需要与抗原呈递细胞(APCs)长时间接触以及持续的信号传导。我们研究了信号传导是否必须不间断才能使T细胞产生细胞因子,或者T细胞激活是否也可能由间断信号的累加导致。在周期性添加和去除一种src激酶抑制剂时,人类CD4(+) T细胞会破坏并重新形成免疫突触,同时中止并重新启动信号转导。值得注意的是,在这些条件下,T细胞最终被激活产生干扰素 -γ,并且尽管有反复中断,所产生的干扰素 -γ的量与总信号传导时间直接相关。我们的结果表明,T细胞激活不需要稳定的免疫突触,并且可以通过间断的信号传导实现。这意味着T细胞可以累加激活信号,这些信号可能是从多个抗原呈递细胞收集而来的。
The activation of biological T cell responses requires prolonged contact with APCs and sustained signaling. We investigated whether signaling must be uninterrupted to commit T cells to cytokine production or whether T cell activation may also result from summation of interrupted signals. Upon periodic addition and removal of a src kinase inhibitor, human CD4(+) T cells destroyed and reformed immunological synapses while aborting and restarting signal transduction. Remarkably, under these conditions, T cells were eventually activated to IFN-gamma production and the amount of IFN-gamma produced was directly related to the total signaling time despite the repeated interruptions. Our results illustrate that T cell activation does not require a stable immunological synapse and can be achieved by interrupted signaling. It is implied that T cells can add activation signals, possibly collected on multiple APCs.