title: Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes.
abstract: 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.
authors.affiliation: Ludwig Institute for Cancer Research, 1200 Brussels, Belgium; Cellular Genetics Unit, Institute of Cellular Pathology, Université catholique de Louvain, 1200 Brussels, Belgium.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Demotte
authors.forename: Vincent
authors.initials: V
authors.lastname: Stroobant
authors.forename: Pierre J
authors.initials: PJ
authors.lastname: Courtoy
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Der Smissen
authors.forename: Didier
authors.initials: D
authors.lastname: Colau
authors.forename: Immanuel F
authors.initials: IF
authors.lastname: Luescher
authors.forename: Claire
authors.initials: C
authors.lastname: Hivroz
authors.forename: Julie
authors.initials: J
authors.lastname: Nicaise
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Squifflet
authors.forename: Michel
authors.initials: M
authors.lastname: Mourad
authors.forename: Danièle
authors.initials: D
authors.lastname: Godelaine
authors.forename: Thierry
authors.initials: T
authors.lastname: Boon
authors.forename: Pierre
authors.initials: P
authors.lastname: van der Bruggen
mesh_terms: D016827:CD8 Antigens / Q000276:immunology / Q000378:metabolism*; D045744:Cell Line, Tumor; D017635:Clonal Anergy / Q000276:immunology*; D005434:Flow Cytometry; D037161:Galectins / Q000378:metabolism; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism*; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000378:metabolism*
chemical_list: D016827:CD8 Antigens; D037161:Galectins; D006680:HLA Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell