Key Points sLeX defines separation in Th lineage–specific polarization among memory T cells. sLeX enriches for Th2/Tc2- and Th17-skewed memory CD4+T cells. sLeX identifies a subset of CD40L-expressing CD8+T cells with poor cytotoxicity. Sialyl Lewis X (sLeX) regulates T cell trafficking from the vasculature into skin and sites of inflammation, thereby playing a critical role in immunity. In healthy persons, only a small proportion of human blood T cells express sLeX, and their function is not fully defined. Using a combination of biochemical and functional studies, we find that human blood sLeX+CD4+T cells comprise a subpopulation expressing high levels of Th2 and Th17 cytokines, chemokine receptors CCR4 and CCR6, and the transcription factors GATA-3 and RORγT. Additionally, sLeX+CD4+T cells exclusively contain the regulatory T cell population (CD127lowCD25high and FOXP3+) and characteristically display immune-suppressive molecules, including the coinhibitor receptors PD-1 and CTLA-4. Among CD8+T cells, sLeX expression distinguishes a subset displaying low expression of cytotoxic effector molecules, perforin and granzyme β, with reduced degranulation and CD57 expression and, consistently, marginal cytolytic capacity after TCR engagement. Furthermore, sLeX+CD8+T cells present a pattern of features consistent with Th cell–like phenotype, including release of pertinent Tc2 cytokines and elevated expression of CD40L. Together, these findings reveal that sLeX display is associated with unique functional specialization of both CD4+ and CD8+T cells and indicate that circulating T cells that are primed to migrate to lesional sites at onset of inflammation are not poised for cytotoxic function.

中文翻译：

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sLeX 表达描绘了人血液中枢 T 细胞和效应记忆 T 细胞的独特功能亚群

关键点 sLeX 定义了记忆 T 细胞之间 Th 谱系特异性极化的分离。sLeX 丰富了 Th2/Tc2 和 Th17 偏向的记忆 CD4+T 细胞。sLeX 鉴定出细胞毒性较差的表达 CD40L 的 CD8+T 细胞子集。Sialyl Lewis X (sLeX) 调节 T 细胞从脉管系统运输到皮肤和炎症部位，从而在免疫中发挥关键作用。在健康人中，只有一小部分人类血液T细胞表达sLeX，并且它们的功能尚未完全确定。通过结合生化和功能研究，我们发现人血 sLeX+CD4+T 细胞包含表达高水平 Th2 和 Th17 细胞因子、趋化因子受体 CCR4 和 CCR6 以及转录因子 GATA-3 和 RORγT 的亚群。此外，sLeX+CD4+T 细胞专门包含调节性 T 细胞群（CD127lowCD25high 和 FOXP3+），并典型地显示免疫抑制分子，包括共抑制剂受体 PD-1 和 CTLA-4。在 CD8+T 细胞中，sLeX 表达区分了一个细胞毒性效应分子、穿孔素和颗粒酶 β 低表达的亚群，脱粒和 CD57 表达减少，TCR 参与后始终保持边缘细胞溶解能力。此外，sLeX+CD8+T 细胞呈现出与 Th 细胞样表型一致的特征模式，包括相关 Tc2 细胞因子的释放和 CD40L 表达的升高。总之，这些发现揭示了 sLeX 展示与 CD4+ 和 CD8+T 细胞的独特功能特化相关，并表明在炎症发作时准备迁移到病变部位的循环 T 细胞并未准备好发挥细胞毒性功能。