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Cell Immunol ; 320: 56-61, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-28916112

RESUMEN

Related studies demonstrate that type 1 diabetes (T1D) is caused by ß-cell antigen specific autoreactive CD8+ T cells. ChgA has recently been identified as the autoantigen in NOD mice and T1D patients. Therefore, attenuating the activation of ChgA specific CD8+ T cells might be a promising target for T1D therapy. The negative co-stimulatory PD-L1 inhibits T cell mediated alloimmunity and induces tolerance. In this experiment, a novel mimovirus encoding ChgA10-19 peptide with PD-L1 was constructed. The NOD.ß2m null HHD mice were administrated with mimovirus transduced DCs. After immunization, the activation and proliferation of CD8+ T cells were detected, diabetes incidence and pancreatic tissue destruction were also analyzed. The results demonstrated that transduced DCs attenuated CD8+ T cell activation and proliferation. In addition, transduced DCs inhibited CD8+ T response to ChgA stimulation, and ameliorated the severity of diabetes. These data suggested that mimovirus transduced DCs might provide novel clues for T1D therapy.


Asunto(s)
Autoantígenos/inmunología , Antígeno B7-H1/inmunología , Linfocitos T CD8-positivos/inmunología , Cromogranina A/inmunología , Células Dendríticas/inmunología , Diabetes Mellitus Tipo 1/terapia , Mimiviridae , Fragmentos de Péptidos , Productos del Gen tat del Virus de la Inmunodeficiencia Humana , Animales , Autoantígenos/genética , Antígeno B7-H1/genética , Proliferación Celular , Células Cultivadas , Cromogranina A/genética , Células Dendríticas/trasplante , Diabetes Mellitus Tipo 1/inmunología , Femenino , Ingeniería Genética , Vectores Genéticos/genética , Humanos , Tolerancia Inmunológica , Células Secretoras de Insulina/inmunología , Activación de Linfocitos , Ratones , Ratones Endogámicos NOD , Mimiviridae/genética , Fragmentos de Péptidos/genética , Transducción Genética , Productos del Gen tat del Virus de la Inmunodeficiencia Humana/genética
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