Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes
Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes
复制标题
DOI：
10.1016/j.immuni.2008.01.011
复制
发表时间：
2008-03-01
期刊：
影响因子：
32.4
通讯作者：
van der Bruggen, Pierre
中科院分区：
文献类型：
--
作者：
Demotte, Nathalie;Stroobant, Vincent;van der Bruggen, Pierre
抗原刺激后数天，人溶细胞性T淋巴细胞（CTL）克隆表现出其效应活性和其与人白细胞抗原（HLA）-肽四聚体的结合降低。我们观察到，当处于这种状态时，CTL失去了T细胞受体（TCR）和CD 8的共定位。用半乳糖凝集素二糖配体恢复效应子功能和TCR-CD 8共定位，表明TCR与半乳糖凝集素的结合在TCR与CD 8的距离中起作用。这些发现似乎适用于体内，因为观察到TCR远离无反应性的人肿瘤浸润淋巴细胞上的CD 8。这些淋巴细胞在用半乳糖凝集素二糖配体离体处理后恢复效应子功能和TCR-CD 8共定位。TCR和CD 8分子的分离可能是肿瘤和其他慢性刺激条件下无反应性的一个主要机制。
For several days after antigenic stimulation, human cytolytic T lymphocyte (CTL) clones exhibit a decrease in their effector activity and in their binding to human leukocyte antigen (HLA)-peptide tetramers. We observed that, when in this state, CTLs lose the colocalization of the T cell receptor (TCR) and CD8. Effector function and TCR-CD8 colocalization were restored with galectin disaccharide ligands, suggesting that the binding of TCR to galectin plays a role in the distancing of TCR from CD8. These findings appear to be applicable in vivo, as TCR was observed to be distant from CD8 on human tumor-infiltrating lymphocytes, which were anergic. These lymphocytes recovered effector functions and TCR-CD8 colocalization after ex vivo treatment with galectin disaccharide ligands. The separation of TCR and CD8 molecules could be one major mechanism of anergy in tumors and other chronic stimulation conditions.