SEA antagonizes the imatinib-meditated inhibitory effects on T cell activation via the TCR signaling pathway.
Biomed Res Int
; 2014: 682010, 2014.
Article
en En
| MEDLINE
| ID: mdl-24524084
ABSTRACT
The BCR-ABL kinase inhibitor imatinib is highly effective in the treatment of chronic myeloid leukemia (CML). However, long-term imatinib treatment induces immunosuppression, which is mainly due to T cell dysfunction. Imatinib can reduce TCR-triggered T cell activation by inhibiting the phosphorylation of tyrosine kinases such as Lck, ZAP70, LAT, and PLC γ 1 early in the TCR signaling pathway. The purpose of this study was to investigate whether the superantigen SEA, a potent T cell stimulator, can block the immunosuppressive effects of imatinib on T cells. Our data show that the exposure of primary human T cells and Jurkat cells to SEA for 24 h leads to the upregulation of the Lck and ZAP70 proteins in a dose-dependent manner. T cells treated with SEA prior to TCR binding had increased the tyrosine phosphorylation of Lck, ZAP70, and PLC γ 1. Pretreatment with SEA prevents the inhibitory effects of imatinib on TCR signaling, which leads to T cell proliferation and IL-2 production. It is conceivable that SEA antagonizes the imatinib-mediated inhibition of T cell activation and proliferation through the TCR signaling pathway.
Texto completo:
1
Bases de datos:
MEDLINE
Métodos Terapéuticos y Terapias MTCI:
Terapias_mente_y_cuerpo
/
Meditacion
Asunto principal:
Piperazinas
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Pirimidinas
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Benzamidas
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Receptores de Antígenos de Linfocitos T
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Transducción de Señal
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Enterotoxinas
Idioma:
En
Revista:
Biomed Res Int
Año:
2014
Tipo del documento:
Article
País de afiliación:
China