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CD4 and CD8 T cells require different membrane gangliosides for activation.


ABSTRACT: 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.

SUBMITTER: Nagafuku M 

PROVIDER: S-EPMC3277553 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

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CD4 and CD8 T cells require different membrane gangliosides for activation.

Nagafuku Masakazu M   Okuyama Kaori K   Onimaru Yuri Y   Suzuki Akemi A   Odagiri Yuta Y   Yamashita Tadashi T   Iwasaki Katsunori K   Fujiwara Michihiro M   Takayanagi Motoaki M   Ohno Isao I   Inokuchi Jin-ichi J  

Proceedings of the National Academy of Sciences of the United States of America 20120117 6


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 fr  ...[more]

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