PMID- 18342010 OWN - NLM STAT- MEDLINE DCOM- 20080513 LR - 20210103 IS - 1097-4180 (Electronic) IS - 1074-7613 (Linking) VI - 28 IP - 3 DP - 2008 Mar TI - Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes. PG - 414-24 LID - 10.1016/j.immuni.2008.01.011 [doi] AB - 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. FAU - Demotte, Nathalie AU - Demotte N AD - Ludwig Institute for Cancer Research, 1200 Brussels, Belgium; Cellular Genetics Unit, Institute of Cellular Pathology, Universite catholique de Louvain, 1200 Brussels, Belgium. FAU - Stroobant, Vincent AU - Stroobant V FAU - Courtoy, Pierre J AU - Courtoy PJ FAU - Van Der Smissen, Patrick AU - Van Der Smissen P FAU - Colau, Didier AU - Colau D FAU - Luescher, Immanuel F AU - Luescher IF FAU - Hivroz, Claire AU - Hivroz C FAU - Nicaise, Julie AU - Nicaise J FAU - Squifflet, Jean-Luc AU - Squifflet JL FAU - Mourad, Michel AU - Mourad M FAU - Godelaine, Daniele AU - Godelaine D FAU - Boon, Thierry AU - Boon T FAU - van der Bruggen, Pierre AU - van der Bruggen P LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Immunity JT - Immunity JID - 9432918 RN - 0 (CD8 Antigens) RN - 0 (Galectins) RN - 0 (HLA Antigens) RN - 0 (Peptides) RN - 0 (Receptors, Antigen, T-Cell) SB - IM MH - CD8 Antigens/immunology/*metabolism MH - Cell Line, Tumor MH - Clonal Anergy/*immunology MH - Flow Cytometry MH - Galectins/metabolism MH - HLA Antigens/immunology MH - Humans MH - Lymphocyte Activation/immunology MH - Lymphocytes, Tumor-Infiltrating/immunology/*metabolism MH - Microscopy, Confocal MH - Microscopy, Electron, Scanning MH - Peptides/immunology MH - Receptors, Antigen, T-Cell/immunology/*metabolism MH - T-Lymphocytes, Cytotoxic/immunology/*metabolism EDAT- 2008/03/18 09:00 MHDA- 2008/05/14 09:00 CRDT- 2008/03/18 09:00 PHST- 2007/07/12 00:00 [received] PHST- 2007/12/18 00:00 [revised] PHST- 2008/01/09 00:00 [accepted] PHST- 2008/03/18 09:00 [pubmed] PHST- 2008/05/14 09:00 [medline] PHST- 2008/03/18 09:00 [entrez] AID - S1074-7613(08)00070-8 [pii] AID - 10.1016/j.immuni.2008.01.011 [doi] PST - ppublish SO - Immunity. 2008 Mar;28(3):414-24. doi: 10.1016/j.immuni.2008.01.011.