CD4 and CD8 T cells require different membrane gangliosides for activation.
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.
Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
Masakazu
M
Nagafuku
Kaori
K
Okuyama
Yuri
Y
Onimaru
Akemi
A
Suzuki
Yuta
Y
Odagiri
Tadashi
T
Yamashita
Katsunori
K
Iwasaki
Michihiro
M
Fujiwara
Motoaki
M
Takayanagi
Isao
I
Ohno
Jin-ichi
J
Inokuchi
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002462:Cell Membrane / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005732:Gangliosides / Q000276:immunology*; D006967:Hypersensitivity / Q000150:complications / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000150:complications / Q000276:immunology / Q000473:pathology; D012799:Sialyltransferases / Q000172:deficiency / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D060168:Thymocytes / Q000166:cytology / Q000276:immunology
D000939:Epitopes; D005732:Gangliosides; D012799:Sialyltransferases; C021343:haematoside synthetase