Epstein–Barr virus-specific CD8+ T lymphocytes from diffuse large B cell lymphoma patients are functionally impaired Academic Article uri icon

abstract

  • SummaryEpstein–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

  • Cárdenas, D
  • Vélez, G
  • Orfao, A
  • Herrera, M V
  • Solano, J
  • Olaya, M
  • Uribe, A M
  • Saavedra, C
  • Duarte, M
  • Rodríguez, M
  • Lopez-Casillas, Marcos
  • Fiorentino, S
  • Quijano, S

publication date

  • 2015

number of pages

  • 10

start page

  • 173

end page

  • 183

volume

  • 182

issue

  • 2