Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.
PLoS One. 2011;6(7):e22560. doi: 10.1371/journal.pone.0022560. Epub 2011 Jul 28.
CD62L/L-selectin is a marker found on naïve T cells and further distinguishes central memory (Tcm, CD62L+) from effector memory (Tem, CD62L-) T cells. The regulation of CD62L plays a pivotal role in controlling the traffic of T lymphocytes to and from peripheral lymph nodes. CD62L is shed from the cell membrane following T cell activation, however, the physiological significance of this event remains to be elucidated. In this study, we utilized in vitro generated anti-tumor antigen T cells and melanoma lines as a model to evaluate the dynamics of CD62L shedding and expression of CD107a as a marker of lytic activity. Upon encounter, with matched tumor lines, antigen reactive T cells rapidly lose CD62L expression and this was associated with the acquisition of CD107a. By CD62L ELISA, we confirmed that this transition was mediated by the shedding of CD62L when T cells encountered specific tumor antigen. The introduction of a shedding resistant mutant of CD62L into the tumor antigen-reactive T cell line JKF6 impaired CD107a acquisition following antigen recognition and this was correlated with decreased lytic activity as measured by (51)Cr release assays. The linkage of the shedding of CD62L from the surface of anti-tumor T cells and acquisition of lytic activity, suggests a new function for CD62L in T cell effector functions and anti-tumor activity.
CD62L/L-选择素是一种在幼稚 T 细胞上发现的标志物，进一步将中央记忆 (Tcm，CD62L+)与效应记忆 (Tem，CD62L-)T 细胞区分开来。CD62L 的调节在控制 T 淋巴细胞进出外周淋巴结的迁移中起着关键作用。T 细胞活化后，CD62L 从细胞膜上脱落，然而，这一事件的生理意义仍有待阐明。在这项研究中，我们利用体外生成的抗肿瘤抗原 T 细胞和黑色素瘤系作为模型，评估 CD62L 脱落和 CD107a 表达作为溶细胞活性标志物的动态变化。当与匹配的肿瘤系相遇时，抗原反应性 T 细胞迅速失去 CD62L 表达，这与 CD107a 的获得有关。通过 CD62L ELISA，我们证实这种转变是由 T 细胞遇到特定肿瘤抗原时 CD62L 的脱落介导的。将 CD62L 的一种脱落抗性突变体引入肿瘤抗原反应性 T 细胞系 JKF6 中，会损害抗原识别后 CD107a 的获得，这与溶细胞活性的降低相关，如 (51)Cr 释放测定所测量的。抗肿瘤 T 细胞表面 CD62L 的脱落与溶细胞活性的获得之间的联系，提示 CD62L 在 T 细胞效应功能和抗肿瘤活性中具有新的功能。
