Molecular mechanisms for the regulation of T cell signals by sphingoglycolipids

分析了复杂神经节苷脂缺乏（GM2/GD2合成酶基因破坏）小鼠的T细胞发育和功能。GM1、asialo-GM1和gGD1b是野生型小鼠T细胞上表达的代表性神经节苷类，在突变型小鼠T细胞上完全检测到。突变小鼠脾脏和胸腺的大小和细胞数量明显减少。当用白细胞介素-2 （IL-2）培养脾脏细胞时，与野生型相比，突变型脾脏细胞的增殖能力降低。相比之下，用豆豆蛋白A或抗cd3交联刺激的增殖没有明显的差异。突变型和野生型小鼠IL-2受体α、β和γ的表达水平几乎相等，T细胞活化后α链的上调也相似。IL-2处理后，突变体脾脏细胞中JAK1、JAK3和STAT5的激活降低，c-fos表达延迟和减少，提示突变体小鼠IL-2信号减弱可能是由于缺乏复杂神经节苷类对IL-2受体功能的调节。

T cell development and function in complex ganglioside-lacking (GM2/GD2 synthase gene-disrupted) mice were analyzed. GM1, asialo-GM1 and gGD1b were representative gangliosides expressed on T cells of the wild type mice, and completely detected on those of mutant mice. The sizes and cell numbers of the mutant mice spleen and thymus were apparently reduced. When spleen cells were cultured with interleukin-2 (IL-2), those from the mutant showed reduced proliferation compared to those from the wild type. In contrast, proliferation by stimulation with concanavalin A or anti-CD3 cross-linking did not exhibit definite differences. Expression levels of IL-2 receptor α, β and γ were almost equivalent, and up-regulation of α chain after T cell activation were also similar between the mutant and wild type mice. Activation of JAK1, JAK3 and STAT5 after IL-2 treatment was reduced, and c-fos expression was delayed and reduced in the spleen cells of the mutant, suggesting that the IL-2 signal was attenuated in the mutant mice probably due to the modulation of the function of IL-2 receptors by the lack of complex gangliosides.