Skewed T-cell differentiation in patients with indolent non-Hodgkin lymphoma reversed by ex vivo T-cell culture with gammac cytokines.
Blood
; 107(2): 602-9, 2006 Jan 15.
Article
em En
| MEDLINE
| ID: mdl-16150945
The unfavorable clinical evolution in indolent non-Hodgkin lymphomas suggests defective control of neoplastic growth by the immune system. To address this issue, we evaluated phenotype, function, and maturation profile of CD4(+) and CD8(+) T cells from peripheral-blood, lymph nodes, or bone marrow of patients with B-cell non-Hodgkin lymphoma (NHL) at diagnosis. T cells from these patients frequently showed an activated but apoptosis-prone phenotype with low frequency of tumor-reactive T cells showing a TH2/Tc2 functional profile in the response to autologous tumor. In peripheral blood or in lymph nodes and bone marrow, and, in comparison to healthy donors, patients' T cells showed a skewed differentiation toward Tnaive and Tcentral memory stages, with low expression of granzyme B and perforin. T-cell culture with autologous tumor in the presence of IL-2, IL-15, and autologous bone marrow-derived cells led to massive T-cell expansion and to differentiation of cytotoxic factor(+) CD8(+) T cells releasing IFN-gamma and killing autologous B-cell tumor in an HLA-class I-restricted fashion. These results suggest impaired T-cell differentiation to effector stage in patients with B-cell NHL, but indicate that T-cell responsiveness to gammac cytokines is retained, thus allowing to promote generation of antitumor T cells for immune intervention.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Linfócitos T Citotóxicos
/
Diferenciação Celular
/
Citocinas
/
Linfoma de Células B
/
Receptores de Interleucina-7
Limite:
Adult
/
Humans
Idioma:
En
Revista:
Blood
Ano de publicação:
2006
Tipo de documento:
Article