CD4 and CD8 T cells require different membrane gangliosides for activation
2012
Nagafuku, Masakazu | Okuyama, Kaori | Onimaru, Yuri | Suzuki, Akemi | Odagiri, Yuta | Yamashita, Tadashi | Iwasaki, Katsunori | Fujiwara, Michihiro | Takayanagi, Motoaki | Ohno, Isao | Inokuchi, Jin-ichi
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.
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