title: The co-receptor BTLA negatively regulates human Vγ9Vδ2 T-cell proliferation: a potential way of immune escape for lymphoma cells.
abstract: Vγ9Vδ2 cells, the major γδ T-cell subset in human peripheral blood, represent a T-cell subset that displays reactivity against microbial agents and tumors. The biology of Vγ9Vδ2 T cells remains poorly understood. We show herein that the interaction between B- and T-lymphocyte attenuator (BTLA) and herpesvirus entry mediator (HVEM) is a major regulator of Vγ9Vδ2 T-cell proliferation control. BTLA was strongly expressed at the surface of resting Vγ9Vδ2 T cells and inversely correlated with T-cell differentiation. BTLA-HVEM blockade by monoclonal antibodies resulted in the enhancement of Vγ9Vδ2 T-cell receptor-mediated signaling, whereas BTLA-HVEM interaction led to a decrease in phosphoantigen-mediated proliferation by inducing a partial S-phase arrest. Our data also suggested that BTLA-HVEM might participate in the control of γδ T-cell differentiation. In addition, the proliferation of autologous γδ T cells after exposition to lymphoma cells was dramatically reduced through BTLA-HVEM interaction. These data suggest that HVEM interaction with BTLA may play a role in lymphomagenesis by interfering with Vγ9Vδ2 T-cell proliferation. Moreover, BTLA stimulation of Vγ9Vδ2 T cells appears as a new possible mechanism of immune escape by lymphoma cells.
authors.affiliation: Institut National de la Santé et de la Recherche Scientifique, U1068, Centre de Recherche en Cancérologie de Marseille-Immunity & Cancer, 27 Bd Lei Roure, Marseille, France. j.gertner-dardenne@hotmail.fr
authors.forename: Julie
authors.initials: J
authors.lastname: Gertner-Dardenne
authors.forename: Cyril
authors.initials: C
authors.lastname: Fauriat
authors.forename: Florence
authors.initials: F
authors.lastname: Orlanducci
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Thibult
authors.forename: Sonia
authors.initials: S
authors.lastname: Pastor
authors.forename: Jude
authors.initials: J
authors.lastname: Fitzgibbon
authors.forename: Reda
authors.initials: R
authors.lastname: Bouabdallah
authors.forename: Luc
authors.initials: L
authors.lastname: Xerri
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D002453:Cell Cycle; D002454:Cell Differentiation; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D053240:Receptors, Tumor Necrosis Factor, Member 14 / Q000276:immunology; D016196:S Phase; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D019139:Tumor Escape; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; C482586:BTLA protein, human; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D053240:Receptors, Tumor Necrosis Factor, Member 14; D014409:Tumor Necrosis Factor-alpha