title: CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression.
abstract: Expression of co-inhibitory molecules is generally associated with T-cell dysfunction in chronic viral infections such as HIV or HCV. However, their relative contribution in the T-cell impairment remains unclear. In the present study, we have evaluated the impact of the expression of co-inhibitory molecules such as 2B4, PD-1 and CD160 on the functions of CD8 T-cells specific to influenza, EBV and CMV. We show that CD8 T-cell populations expressing CD160, but not PD-1, had reduced proliferation capacity and perforin expression, thus indicating that the functional impairment in CD160(+) CD8 T cells may be independent of PD-1 expression. The blockade of CD160/CD160-ligand interaction restored CD8 T-cell proliferation capacity, and the extent of restoration directly correlated with the ex vivo proportion of CD160(+) CD8 T cells suggesting that CD160 negatively regulates TCR-mediated signaling. Furthermore, CD160 expression was not up-regulated upon T-cell activation or proliferation as compared to PD-1. Taken together, these results provide evidence that CD160-associated CD8 T-cell functional impairment is independent of PD-1 expression.
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Selena
authors.initials: S
authors.lastname: Viganò
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Riddhima
authors.initials: R
authors.lastname: Banga
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Florence
authors.initials: F
authors.lastname: Bellanger
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Céline
authors.initials: C
authors.lastname: Pellaton
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Alex
authors.initials: A
authors.lastname: Farina
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Comte
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland; Swiss Vaccine Research Institute, Lausanne University Hospital, University of Lausanne, Lausanne, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Harari
authors.affiliation: Division of Immunology and Allergy, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
authors.forename: Matthieu
authors.initials: M
authors.lastname: Perreau
mesh_terms: D015703:Antigens, CD / Q000378:metabolism*; D015153:Blotting, Western; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000378:metabolism; D016174:Hepacivirus / Q000502:physiology; D006526:Hepatitis C / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C114505:CD160 protein, human; D058851:GPI-Linked Proteins; D061026:Programmed Cell Death 1 Receptor; D011971:Receptors, Immunologic