Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes

被引：155

作者：

Demotte, Nathalie ^{[1
,2
]}

Stroobant, Vincent ^{[1
,2
]}

Courtoy, Pierre J. ^{[3
]}

Van Der Smissen, Patrick ^{[3
]}

Colau, Didier ^{[1
,2
]}

Luescher, Immanuel F. ^{[4
]}

Hivroz, Claire ^{[5
]}

Nicaise, Julie ^{[1
,2
]}

Squifflet, Jean-Luc ^{[6
]}

Mourad, Michel ^{[7
]}

Godelaine, Danile ^{[1
,2
]}

Boon, Thierry ^{[1
,2
]}

van der Bruggen, Pierre ^{[1
,2
]}

机构：

[1] Ludwig Inst Canc Res, B-1200 Brussels, Belgium

[2] Catholic Univ Louvain, Inst Cell Pathol, Cell Genet Unit, B-1200 Brussels, Belgium

[3] Catholic Univ Louvain, Inst Cell Pathol, Cell Biol Unit, B-1200 Brussels, Belgium

[4] Ludwig Inst Canc Res, CH-1066 Epalinges, Switzerland

[5] Inst Curie, INSERM, U653, F-75005 Paris, France

[6] Catholic Univ Louvain, Clin Univ St Luc, Dept Gynaecol, B-1200 Brussels, Belgium

[7] Catholic Univ Louvain, Clin Univ St Luc, Dept Transplant Surg, B-1200 Brussels, Belgium

来源：

IMMUNITY | 2008年 / 28卷 / 03期

关键词：

D O I：

10.1016/j.immuni.2008.01.011

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：414 / 424

页数：11

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