title: The activatory receptor 2B4 is expressed in vivo by human CD8+ effector alpha beta T cells.
abstract: The membrane receptor 2B4 is a CD2 family member that is involved in lymphocyte activation. A fraction of human CD8+ alphabeta T cells up-regulate 2B4 in vivo, and here we demonstrate that this correlates with the acquisition of effector cell properties such as granzyme B and perforin expression, rapid IFN-gamma production, and down-regulation of the lymph node homing chemokine receptor CCR7. In PBLs from healthy donors, cytomegalovirus-specific effector T cells were 2B4 positive, whereas naive melanoma Ag (Melan-A/melanoma Ag recognized by T cells-1)-specific T cells were 2B4 negative. In melanoma patients, Melan-A-specific T cells up-regulated 2B4 in parallel with in vivo differentiation. This occurred in PBLs after vaccination with Melan-A peptides and in tumor-infiltrated lymph nodes, likely through disease-associated activation of Melan-A-specific T cells. Thus, 2B4 expression correlates with CD8+ T cell differentiation in vivo.
authors.affiliation: Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. daniel.speiser@hospvd.ch
authors.forename: D E
authors.initials: DE
authors.lastname: Speiser
authors.forename: M
authors.initials: M
authors.lastname: Colonna
authors.forename: M
authors.initials: M
authors.lastname: Ayyoub
authors.forename: M
authors.initials: M
authors.lastname: Cella
authors.forename: M J
authors.initials: MJ
authors.lastname: Pittet
authors.forename: P
authors.initials: P
authors.lastname: Batard
authors.forename: D
authors.initials: D
authors.lastname: Valmori
authors.forename: P
authors.initials: P
authors.lastname: Guillaume
authors.forename: D
authors.initials: D
authors.lastname: Liénard
authors.forename: J C
authors.initials: JC
authors.lastname: Cerottini
authors.forename: P
authors.initials: P
authors.lastname: Romero
mesh_terms: D015703:Antigens, CD; D000951:Antigens, Neoplasm; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D018984:Epitopes, T-Lymphocyte / Q000032:analysis; D053804:Granzymes; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation; D058965:MART-1 Antigen; D008545:Melanoma / Q000276:immunology / Q000628:therapy; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D009363:Neoplasm Proteins / Q000276:immunology / Q000627:therapeutic use; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D011971:Receptors, Immunologic / Q000096:biosynthesis*; D012697:Serine Endopeptidases / Q000096:biosynthesis; D000071176:Signaling Lymphocytic Activation Molecule Family; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D015703:Antigens, CD; D000951:Antigens, Neoplasm; C084093:CD244 protein, human; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D058965:MART-1 Antigen; C548667:MLANA protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D052899:Pore Forming Cytotoxic Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic; D000071176:Signaling Lymphocytic Activation Molecule Family; D054353:Perforin; D007371:Interferon-gamma; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases