First Author | Nagafuku M | Year | 2012 |
Journal | Proc Natl Acad Sci U S A | Volume | 109 |
Issue | 6 | Pages | E336-42 |
PubMed ID | 22308377 | Mgi Jnum | J:182621 |
Mgi Id | MGI:5316179 | Doi | 10.1073/pnas.1114965109 |
Citation | Nagafuku M, et al. (2012) CD4 and CD8 T cells require different membrane gangliosides for activation. Proc Natl Acad Sci U S A 109(6):E336-42 |
abstractText | Initial events of T-cell activation involve movement of the T-cell receptor into lipid rafts. Gangliosides are major components of lipid rafts. While investigating T-cell activation in ganglioside-deficient mice, we observed that CD4(+) and CD8(+) T cells required different ganglioside subsets for activation. Activation of CD4(+) T cells from GM3 synthase-null mice, deficient in GM3-derived gangliosides, is severely compromised, whereas CD8(+) T-cell activation is normal. Conversely, in cells from GM2/GD2 synthase-null mice, expressing only GM3 and GD3, CD4(+) T-cell activation is normal, whereas CD8(+) T-cell activation is deficient. Supplementing the cells with the corresponding missing gangliosides restores normal activation. GM3 synthase-null mice do not develop experimental asthma. Distinct expression patterns of ganglioside species in CD4(+) T and CD8(+) T cells, perhaps in uniquely functional lipid rafts, define immune functions in each T-cell subset. Control of ganglioside expression would offer a strategy targeting for specific T-cell subpopulations to treat immune diseases. |