Immunity：逆转肿瘤浸润淋巴细胞免疫无能

来源：Immunity 作者：无发布时间：2008-06-06

浸润肿瘤组织中的CD8+  T细胞会出现免疫无能从而失去抗肿瘤的能力。在抗原刺激后，CD8+  T细胞也会在一段时间处于免疫无能的状态。

比利时布鲁塞尔路德维格肿瘤研究所的科学家Van  der  Bruggen及其同事研究发现，免疫无能的CD8+  T细胞不仅分泌的IFN-γ大量减少，而且与四聚体的结合能力大大下降。FRET实验表明，与四聚体亲和力低的细胞膜表面的TCR和CD8位置不再重叠而是处于分离状态，却出现了TCR与galectin的位置重叠。相反，与四聚体亲和力高的细胞膜表面的TCR和CD8的位置重叠，并且TCR和CD8均不与galectin重叠。经galectin的二糖配体处理，免疫无能的CD8+  T细胞不仅膜表面的TCR和CD8重新同位化，而且恢复了对四聚体的亲和力以及高表达IFN-γ。因此，galectin与TCR结合促使TCR和CD8分离，从而导致细胞的免疫无能。研究还发现，肿瘤浸润的CD8+  T细胞也出现了TCR和CD8的位置分离。同样，经galectin的二糖配体处理，这些肿瘤浸润CD8+  T细胞膜表面的TCR和CD8位置的同位化，以及它们的功能都得到了恢复。研究人员指出，使用galectin的二糖配体治疗肿瘤患者也许可以恢复CD8+  T细胞的抗肿瘤作用。

相关论文发表在《免疫》（Immunity）杂志上。（科学新闻杂志  王炯坤/编译）

原始出处：

Immunity, Vol 28, 414-424, 14 March 2008

Article

Restoring the Association of the T Cell Receptor with CD8 Reverses Anergy in Human Tumor-Infiltrating Lymphocytes

Nathalie Demotte,1,2 Vincent Stroobant,1,2 Pierre J. Courtoy,3 Patrick Van Der Smissen,3 Didier Colau,1,2 Immanuel F. Luescher,4 Claire Hivroz,5 Julie Nicaise,1,2 Jean-Luc Squifflet,6 Michel Mourad,7 Danièle Godelaine,1,2 Thierry Boon,1,2 and Pierre van der Bruggen1,2,

1 Ludwig Institute for Cancer Research, 1200 Brussels, Belgium
2 Cellular Genetics Unit, Institute of Cellular Pathology, Université catholique de Louvain, 1200 Brussels, Belgium
3 Cell Biology Unit, Institute of Cellular Pathology, Université catholique de Louvain, 1200 Brussels, Belgium
4 Ludwig Institute for Cancer Research, 1066 Epalinges, Switzerland
5 INSERM U653, Institut Curie, 75005 Paris, France
6 Department of Gynaecology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, 1200 Brussels, Belgium
7 Department of Transplant Surgery, Cliniques universitaires Saint-Luc, Université catholique de Louvain, 1200 Brussels, Belgium

Corresponding author
Pierre van der Bruggen
pierre.vanderbruggen@bru.licr.org

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.

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