Division of Glycopathology, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Sendai 981-8558, Japan.
Proc Natl Acad Sci U S A. 2012 Feb 7;109(6):E336-42. doi: 10.1073/pnas.1114965109. Epub 2012 Jan 17.
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.
T 细胞活化的初始事件涉及 T 细胞受体进入脂筏。神经节苷脂是脂筏的主要组成部分。在研究神经节苷脂缺陷型小鼠中的 T 细胞活化时，我们观察到 CD4(+)和 CD8(+)T 细胞激活需要不同的神经节苷脂亚群。GM3 合成酶缺陷型小鼠（GM3 衍生的神经节苷脂缺乏）中 CD4(+)T 细胞的激活严重受损，而 CD8(+)T 细胞的激活则正常。相反，在 GM2/GD2 合成酶缺陷型小鼠（仅表达 GM3 和 GD3）的细胞中，CD4(+)T 细胞的激活正常，而 CD8(+)T 细胞的激活则不足。用相应缺失的神经节苷脂补充细胞可恢复正常激活。GM3 合成酶缺陷型小鼠不会发展实验性哮喘。CD4(+)T 和 CD8(+)T 细胞中神经节苷脂种类的不同表达模式，可能在功能独特的脂筏中，定义了每个 T 细胞亚群的免疫功能。控制神经节苷脂的表达将为针对特定 T 细胞亚群的治疗免疫疾病提供一种策略。
