PDF(Pubmed)
Abstract：
Sialic acids are found as terminal sugars on glycan structures on cellular surfaces. T cells carry these sialoglycans abundantly, and they are thought to serve multiple functions in cell adhesion, cell migration, and protection from complement attack. We studied the role of sialoglycans on T cells in a mouse model with a T cell-specific deletion of cytidine monophosphate-sialic acid synthase (CMAS), the enzyme that is crucial for the synthesis of sialoglycans. These mice showed a T-cell deficiency in peripheral lymphoid organs. Many T cells with an undeleted Cmas allele were found in the periphery, suggesting that they escaped the Cre-mediated deletion. The remaining peripheral T cells of T cell-specific Cmas KO mice had a memory-like phenotype. Additional depletion of the complement factor C3 could not rescue the phenotype, showing that the T-cell defect was not caused by a host complement activity. Cmas-deficient T cells showed a high level of activated caspase 3, indicating an ongoing apoptosis. In bone marrow chimeric cellular transfer experiments, we observed a strong competitive disadvantage of Cmas-deficient T cells compared to wild-type T cells. These results show that sialoglycans on the surface of T cells are crucial for T-cell survival and maintenance. This function has not been recognized before and is similar to the function of sialoglycans on B cells.
摘要：
唾液酸作为末端糖存在于细胞表面上的聚糖结构上。T细胞大量携带这些唾液酸聚糖，它们被认为在细胞粘附中具有多种功能，细胞迁移，保护免受补充攻击。我们研究了唾液酸聚糖在小鼠模型中对T细胞的作用，该模型具有胞苷一磷酸-唾液酸合酶（CMAS）的T细胞特异性缺失，对唾液酸聚糖合成至关重要的酶。这些小鼠在外周淋巴器官中表现出T细胞缺乏。在外围发现了许多具有未删除的Cmas等位基因的T细胞，表明他们逃脱了Cre介导的缺失.T细胞特异性CmasKO小鼠的其余外周T细胞具有记忆样表型。补体因子C3的额外消耗不能挽救表型，表明T细胞缺陷不是由宿主补体活性引起的。Cmas缺陷型T细胞显示高水平的活化的半胱天冬酶3,表明正在进行的细胞凋亡。在骨髓嵌合细胞转移实验中，与野生型T细胞相比，我们观察到Cmas缺陷型T细胞具有很强的竞争劣势。这些结果表明，T细胞表面的唾液酸聚糖对于T细胞的存活和维持至关重要。此功能以前尚未被识别，并且类似于唾液酸聚糖在B细胞上的功能。
