Increased T-cell responses to Epstein-Barr virus with high viral load in patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma

Leuk Lymphoma. 2015 Apr;56(4):1072-8. doi: 10.3109/10428194.2014.938326. Epub 2014 Aug 13.

Abstract

The immunological status of patients with Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL) without obvious immunodeficiency has not been elucidated. A multicenter prospective study was conducted to assess pretreatment T-cell responses to EBV, EBV-DNA load and anti-EBV antibody in these patients. The proliferative and interferon (IFN)-γ-producing capacity of T-cells in response to autologous B-lymphoblastoid cell lines was determined using carboxyfluorescein diacetate succinimidyl ester (CFSE)-based assay. Frequencies of EBV-specific CD4+ T-cells in patients with EBV+ DLBCL (n = 13) were significantly higher than in healthy controls (HCs) (n = 16) after both ex vivo and in vitro stimulation. Frequencies of EBV-specific CD8+ T-cells in patients with EBV+ DLBCL tended to be higher than in HCs after in vitro stimulation. Patients with EBV+ DLBCL also showed increased immunoglobulin G (IgG) responses to lytic EBV-encoded antigens. Pretreatment plasma EBV-DNA level was significantly higher in patients with EBV+ DLBCL than in patients with EBV- DLBCL or HCs. In conclusion, EBV-specific T-cells showed increased reactivity, accompanied by higher levels of plasma virus DNA in patients with EBV+ DLBCL.

Keywords: EBV-DNA load; EBV-positive diffuse large B-cell lymphoma; IFN-γ secretion; T-cell proliferation; immune response.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Viral / immunology
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Proliferation
  • Cells, Cultured
  • DNA, Viral / blood
  • DNA, Viral / genetics
  • DNA, Viral / immunology
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Infections / virology
  • Female
  • Flow Cytometry
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / immunology*
  • Herpesvirus 4, Human / physiology
  • Host-Pathogen Interactions / immunology
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / therapeutic use
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Lymphocyte Count
  • Lymphoma, Large B-Cell, Diffuse / complications
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / immunology*
  • Male
  • Middle Aged
  • Prospective Studies
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Viral Load / immunology*

Substances

  • Antibodies, Viral
  • DNA, Viral
  • Immunoglobulin G
  • Interferon-gamma