Epstein-Barr virus-specific CD8(+) T lymphocytes from diffuse large B cell lymphoma patients are functionally impaired.
Clin Exp Immunol
; 182(2): 173-83, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-26174440
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)-Vß17 and CD8(+)/TNF-α(+) T cells with TCR-Vß5·2, Vß9 and Vß18 in response to EBV. Notably, the production of TNF-α was undetectable among TCR-Vß5·3(+), Vß11(+), Vß12(+), Vß16(+) and Vß23(+) 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.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfoma Difuso de Grandes Células B
/
Herpesvirus Humano 4
/
Linfócitos T CD8-Positivos
/
Infecções por Vírus Epstein-Barr
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article