Demotte Nathalie, Stroobant Vincent, Courtoy Pierre J, Van Der Smissen Patrick, Colau Didier, Luescher Immanuel F, Hivroz Claire, Nicaise Julie, Squifflet Jean-Luc, Mourad Michel, Godelaine Danièle, Boon Thierry, van der Bruggen Pierre
Ludwig Institute for Cancer Research, 1200 Brussels, Belgium; Cellular Genetics Unit, Institute of Cellular Pathology, Université catholique de Louvain, 1200 Brussels, Belgium.
Immunity. 2008 Mar;28(3):414-24. doi: 10.1016/j.immuni.2008.01.011.
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.
在抗原刺激后的数天里，人细胞毒性T淋巴细胞（CTL）克隆的效应子活性及其与人白细胞抗原（HLA）-肽四聚体的结合能力均会下降。我们观察到，处于这种状态时，CTL会失去T细胞受体（TCR）与CD8的共定位。半乳糖凝集素二糖配体可恢复效应子功能和TCR-CD8共定位，这表明TCR与半乳糖凝集素的结合在TCR与CD8的分离中起作用。这些发现似乎在体内也适用，因为在人肿瘤浸润淋巴细胞（这些细胞处于无反应状态）上观察到TCR与CD8分离。在用半乳糖凝集素二糖配体进行离体处理后，这些淋巴细胞恢复了效应子功能和TCR-CD8共定位。TCR和CD8分子的分离可能是肿瘤及其他慢性刺激条件下无反应状态的一种主要机制。
