Structure and function of lipid rafts in human activated T cells
Structure and function of lipid rafts in human activated T cells
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DOI：
10.1093/intimm/dxh257
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发表时间：
2005-06-01
影响因子：
4.4
通讯作者：
Kosugi, A
中科院分区：
文献类型：
--
作者：
Tani-ichi, S;Maruyama, K;Kosugi, A
脂筏是一种特殊的膜微结构域，富含鞘脂和胆固醇，已被证明在T细胞中起信号传导平台的作用。已知在人类T细胞活化后，表面筏表达增加，这种增加的筏表达可能解释了有效的信号传导能力和减少对效应和/或活化T细胞共刺激的依赖性。然而，筏介导的激活T细胞的信号传导能力仍有待阐明。在本研究中，我们分析了人活化T细胞中脂筏的结构和功能。我们证明了筏蛋白成分在激活后随着脂质含量的增加而发生显著变化。用抗cd3和抗cd28抗体刺激的T细胞不仅表面单唾液神经节脂苷GM1表达增加，而且筏相关脂质如鞘磷脂、胆固醇和鞘脂糖的总量也增加。激活后增加的Raft蛋白包括Csk、Csk结合蛋白和Fyn，已知参与T细胞激活负调控的分子。与这些蛋白表达的增加一致，tcr介导的Ca2+反应，依赖于筏完整性的反应，在活化的T细胞中明显被抑制。因此，人活化T细胞中的脂筏的结构和功能似乎与幼稚T细胞中的脂筏有很大的不同。此外，人类活化的T细胞对TCR再刺激的信号传导具有相对抗性，至少是暂时的，尽管它们的筏表达增加了。
Lipid rafts, specialized membrane microdomains enriched in sphingolipids and cholesterol, have been shown to function as signaling platforms in T cells. Surface raft expression is known to be increased in human T cells upon activation, and this increased raft expression may account for efficient signaling capability and decreased dependency for co-stimulation in effector and/or activated T cells. However, raft-mediated signaling ability in activated T cells remains to be clarified. In this study, we analyzed the structure and function of lipid rafts in human activated T cells. We demonstrated that raft protein constituents are dramatically changed after activation along with an increase in lipid contents. T cells stimulated with anti-CD3 plus anti-CD28 antibodies showed an increase not only in surface monosialoganglioside GM1 expression but also in total amounts of raft-associated lipids such as sphingomyelin, cholesterol and glycosphingolipids. Raft proteins increased after activation include Csk, Csk-binding protein and Fyn, the molecules known to be involved in negative regulation of T cell activation. Consistent with the increase in expression of these proteins, TCR-mediated Ca2+ response, a response dependent on raft integrity, was clearly inhibited in activated T cells. Thus, the structure and function of lipid rafts in human activated T cells seem to be quite distinct from those in naive T cells. Further, human activated T cells are relatively resistant to signaling, at least transiently, by TCR re-stimulation even though their raft expression is increased.