Restoring the association of the T cell receptor with CD8 reverses anergy in human tumor-infiltrating lymphocytes.
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.
Demotte
Nathalie
N
Ludwig Institute for Cancer Research, 1200 Brussels, Belgium; Cellular Genetics Unit, Institute of Cellular Pathology, Université catholique de Louvain, 1200 Brussels, Belgium.
Stroobant
Vincent
V
Courtoy
Pierre J
PJ
Van Der Smissen
Patrick
P
Colau
Didier
D
Luescher
Immanuel F
IF
Hivroz
Claire
C
Nicaise
Julie
J
Squifflet
Jean-Luc
JL
Mourad
Michel
M
Godelaine
Danièle
D
Boon
Thierry
T
van der Bruggen
Pierre
P
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*
D016827:CD8 Antigens; D037161:Galectins; D006680:HLA Antigens; D010455:Peptides; D011948:Receptors, Antigen, T-Cell