title: Epstein-Barr virus-specific CD8(+) T lymphocytes from diffuse large B cell lymphoma patients are functionally impaired.
abstract: Epstein-Barr virus (EBV) is a persistent virus with oncogenic capacity that has been implicated in the development of aggressive B cell lymphomas, primarily in immunosuppressed individuals, although it can be present in immunocompetent individuals. Changes in the function and clonal diversity of T lymphocytes might be implied by viral persistence and lymphoma development. The aim of the present study was to evaluate the frequency, phenotype, function and clonotypical distribution of EBV-specific T cells after peripheral blood stimulation with a virus lysate in newly diagnosed patients with diffuse large B cell lymphoma (DLBCL) aged more than 50 years without prior histories of clinical immunosuppression compared with healthy controls. Our results showed impaired EBV-specific immune responses among DLBCL patients that were associated primarily with decreased numbers of central and effector memory CD8(+) T lymphocytes. In contrast to healthy controls, only a minority of the patients showed CD4(+)/tumour necrosis factor (TNF)-α(+) T cells expressing T cell receptor (TCR)-Vβ17 and CD8(+)/TNF-α(+) T cells with TCR-Vβ5·2, Vβ9 and Vβ18 in response to EBV. Notably, the production of TNF-α was undetectable among TCR-Vβ5·3(+), Vβ11(+), Vβ12(+), Vβ16(+) and Vβ23(+) CD8(+) T cells. In addition, we observed decreased numbers of CD4(+)/TNF-α(+) and CD8(+)/TNF-α(+), CD8(+)/interleukin (IL)-2(+) and CD8(+)/TNF-α(+)/IL-2(+) T lymphocytes in the absence of T cells capable of producing TNF-α, IL-2 and IFN-γ after EBV stimulation simultaneously. Moreover, DLBCL patients displayed higher IL-10 levels both under baseline conditions and after EBV stimulation. These findings were also observed in patients with positive EBV viral loads. Prospective studies including a large number of patients are needed to confirm these findings.
authors.affiliation: Grupo De Inmunobiología Y Biología Celular Departamento De Microbiología Facultad De Ciencias Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: D
authors.initials: D
authors.lastname: Cárdenas
authors.affiliation: Grupo De Inmunobiología Y Biología Celular Departamento De Microbiología Facultad De Ciencias Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: G
authors.initials: G
authors.lastname: Vélez
authors.affiliation: Servicio General De Citometría Y Departamento De Medicina, Centro De Investigación Del Cáncer (Instituto De Biología Molecular Y Celular Del Cáncer and IBSAL; CSIC-USAL), Universidad De Salamanca, Salamanca, España.
authors.forename: A
authors.initials: A
authors.lastname: Orfao
authors.affiliation: Servicio De Hematología Hospital Universitario San Ignacio-Centro De Oncología Javeriano.
authors.forename: M V
authors.initials: MV
authors.lastname: Herrera
authors.affiliation: Servicio De Hematología Hospital Universitario San Ignacio-Centro De Oncología Javeriano.
authors.forename: J
authors.initials: J
authors.lastname: Solano
authors.affiliation: Departamento de Patología, Pontificia Universidad Javeriana, Hospital Universitario San Ignacio.
authors.forename: M
authors.initials: M
authors.lastname: Olaya
authors.affiliation: Departamento de Patología, Pontificia Universidad Javeriana, Hospital Universitario San Ignacio.
authors.forename: A M
authors.initials: AM
authors.lastname: Uribe
authors.affiliation: Grupo De Patología Fundación Santa Fe De Bogotá
authors.forename: C
authors.initials: C
authors.lastname: Saavedra
authors.affiliation: Servicio De Hematología Fundación Santa Fe De Bogotá, Bogotá, Colombia.
authors.forename: M
authors.initials: M
authors.lastname: Duarte
authors.affiliation: Servicio De Hematología Fundación Santa Fe De Bogotá, Bogotá, Colombia.
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez
authors.affiliation: Fundación Cardiovascular De Colombia, Floridablanca, Colombia.
authors.forename: M
authors.initials: M
authors.lastname: López
authors.affiliation: Grupo De Inmunobiología Y Biología Celular Departamento De Microbiología Facultad De Ciencias Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: S
authors.initials: S
authors.lastname: Fiorentino
authors.affiliation: Grupo De Inmunobiología Y Biología Celular Departamento De Microbiología Facultad De Ciencias Pontificia Universidad Javeriana, Bogotá, Colombia.
authors.forename: S
authors.initials: S
authors.lastname: Quijano
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D005260:Female; D005434:Flow Cytometry; D004854:Herpesvirus 4, Human / Q000276:immunology* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D018655:Lymphocyte Count; D016403:Lymphoma, Large B-Cell, Diffuse / Q000097:blood / Q000276:immunology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D019562:Viral Load / Q000276:immunology
chemical_list: D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: EBV; TCR-Vβ repertoire; diffuse large B cell lymphoma; memory and effector T lymphocytes; soluble cytokines