International Immunology Advance Access originally published online on June 20, 2005
International Immunology 2005 17(6):749-758; doi:10.1093/intimm/dxh257
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Structure and function of lipid rafts in human activated T cells
1 Department of Immunobiology, Medical Technology and Science, Osaka University Graduate School of Medicine, 1-7, Yamadaoka, Suita, Osaka 565-0871, Japan
2 Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Hokkaido, Japan
3 Biomembrane Research Group, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
4 Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan
5 Core Research for Evolutional Science and Technology program, Japan Science and Technology Corporation, Saitama, Japan
Correspondence to: A. Kosugi; E-mail: kosugi{at}nature.email.ne.jp
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.
Keywords: Cbp, cholesterol, GM1, negative regulation, TCR signaling
Transmitting editor: A. Singer
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