生物谷報(bào)道：浸潤(rùn)腫瘤組織中的CD8+ T細(xì)胞會(huì)出現(xiàn)免疫無(wú)能從而失去抗腫瘤的能力,。在抗原刺激后,，CD8+ T細(xì)胞也會(huì)在一段時(shí)間處于免疫無(wú)能的狀態(tài),。
比利時(shí)布魯塞爾路德維格腫瘤研究所的科學(xué)家Van der Bruggen及其同事研究發(fā)現(xiàn)，免疫無(wú)能的CD8+ T細(xì)胞不僅分泌的IFN-γ大量減少,，而且與四聚體的結(jié)合能力大大下降,。FRET實(shí)驗(yàn)表明，與四聚體親和力低的細(xì)胞膜表面的TCR和CD8位置不再重疊而是處于分離狀態(tài),，卻出現(xiàn)了TCR與galectin的位置重疊,。相反，與四聚體親和力高的細(xì)胞膜表面的TCR和CD8的位置重疊,，并且TCR和CD8均不與galectin重疊,。經(jīng)galectin的二糖配體處理，免疫無(wú)能的CD8+ T細(xì)胞不僅膜表面的TCR和CD8重新同位化,，而且恢復(fù)了對(duì)四聚體的親和力以及高表達(dá)IFN-γ,。因此，galectin與TCR結(jié)合促使TCR和CD8分離，從而導(dǎo)致細(xì)胞的免疫無(wú)能,。研究還發(fā)現(xiàn),，腫瘤浸潤(rùn)的CD8+ T細(xì)胞也出現(xiàn)了TCR和CD8的位置分離。同樣,，經(jīng)galectin的二糖配體處理,，這些腫瘤浸潤(rùn)C(jī)D8+ T細(xì)胞膜表面的TCR和CD8位置的同位化，以及它們的功能都得到了恢復(fù),。研究人員指出,，使用galectin的二糖配體治療腫瘤患者也許可以恢復(fù)CD8+ T細(xì)胞的抗腫瘤作用。
相關(guān)論文發(fā)表在《免疫》（Immunity）雜志上,。（科學(xué)新聞雜志 王炯坤/編譯）
生物谷推薦原始出處：
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
[email protected]
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.
