title: Structure and function of lipid rafts in human activated T cells.
abstract: 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 Ca(2+) 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.
authors.affiliation: Department of Immunobiology, Medical Technology and Science, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
authors.forename: Shizue
authors.initials: S
authors.lastname: Tani-ichi
authors.forename: Koji
authors.initials: K
authors.lastname: Maruyama
authors.forename: Nami
authors.initials: N
authors.lastname: Kondo
authors.forename: Masakazu
authors.initials: M
authors.lastname: Nagafuku
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kabayama
authors.forename: Jin-ichi
authors.initials: J
authors.lastname: Inokuchi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Shimada
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Ohno-Iwashita
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Sunao
authors.initials: S
authors.lastname: Kawano
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kosugi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism; D000906:Antibodies; D000911:Antibodies, Monoclonal; D020013:Calcium Signaling / Q000276:immunology; D002478:Cells, Cultured; D002784:Cholesterol / Q000276:immunology / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000276:immunology / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D008563:Membrane Lipids / Q000276:immunology / Q000378:metabolism*; D021962:Membrane Microdomains / Q000276:immunology*; D008565:Membrane Proteins / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell; D013107:Sphingolipids / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019061:src-Family Kinases / Q000276:immunology / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000906:Antibodies; D000911:Antibodies, Monoclonal; D008563:Membrane Lipids; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D013107:Sphingolipids; D005677:G(M1) Ganglioside; D002784:Cholesterol; D019061:src-Family Kinases