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Leuk Lymphoma ; 55(5): 1144-50, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-23841510

RESUMO

Abstract Everolimus (RAD-001) has recently been used as an immunosuppressive drug to treat patients after hematopoietic stem cell transplant (HSCT), thereby reducing cyclosporine-related nephrotoxicity. We studied the immunomodulatory effect of everolimus on mitogen-stimulated and particularly cytomegalovirus (CMV)-specific cytotoxic T cells. Proliferation of CD4(+) and CD8(+) T cells stimulated with staphylococcal endotoxin B and phytohemagglutinin was strongly inhibited at very low doses. Proliferation of CMV-specific CD8(+) T cells could be completely suppressed. Similarly, the frequency of CMV-specific, cytokine-secreting and CD137-expressing CD8(+) T cells decreased in a dose-dependent manner. However, interferon-γ (IFN-γ) secretion by CMV-specific CD8(+) T cells remained unchanged, as could be demonstrated by intracellular cytokine staining. As reactivation of CMV plays a pivotal role in the outcome of patients after HSCT, attention must be paid to early detection and preemptive treatment of CMV reactivity in patients treated with everolimus.


Assuntos
Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Imunossupressores/farmacologia , Sirolimo/análogos & derivados , Especificidade do Receptor de Antígeno de Linfócitos T/efeitos dos fármacos , Especificidade do Receptor de Antígeno de Linfócitos T/imunologia , Linfócitos T CD8-Positivos/metabolismo , Everolimo , Humanos , Concentração Inibidora 50 , Interferon gama/biossíntese , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Fosfoproteínas/imunologia , Sirolimo/farmacologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismo , Proteínas da Matriz Viral/imunologia
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