CD4 and CD8 T cells require different membrane gangliosides for activation
CD4 and CD8 T cells require different membrane gangliosides for activation
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DOI：
10.1073/pnas.1114965109
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发表时间：
2012-02-07
影响因子：
11.1
通讯作者：
Inokuchi, Jin-ichi
中科院分区：
文献类型：
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作者：
Nagafuku, Masakazu;Okuyama, Kaori;Inokuchi, Jin-ichi
T细胞活化的初始事件涉及T细胞受体进入脂筏的运动。神经节苷脂是脂筏的主要成分。在研究神经节苷脂缺乏小鼠的T细胞活化时，我们观察到CD 4（+）和CD 8（+）T细胞需要不同的神经节苷脂亚群才能活化。缺乏GM 3衍生神经节苷脂的GM 3转移酶缺失小鼠的CD 4（+）T细胞活化严重受损，而CD 8（+）T细胞活化正常。相反，在来自GM 2/GD 2转肽酶缺失小鼠的细胞中，仅表达GM 3和GD 3，CD 4（+）T细胞活化是正常的，而CD 8（+）T细胞活化是缺陷的。用相应缺失的神经节苷脂补充细胞恢复正常激活。GM 3 β-淀粉酶缺失小鼠不发生实验性哮喘。CD 4（+）T和CD 8（+）T细胞中神经节苷脂种类的不同表达模式，可能在独特功能的脂筏中，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提供靶向特定T细胞亚群以治疗免疫性疾病的策略。
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 sub-populations to treat immune diseases.