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Genet Mol Res ; 14(3): 11444-55, 2015 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-26436385

RESUMO

We determined whether genetically engineered immature dendritic cells (imDCs) mediated by lentiviral vectors alleviate acute graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation (allo-BMT) in mice. We introduced the mouse chemokine receptor 7 (Ccr7) gene into the bone marrow-derived imDCs of C57BL/6 mice to construct genetically engineered imDCs. A 1:1 mixture of bone marrow and spleen cells from the donors was injected into the recipients, which were divided into four groups: radiation, transplantation, empty vector, and transgenic imDC groups. Symptoms, clinical scores, GVHD pathological changes, and survival times and rates of recipients were recorded; secretion of IFN-γ and IL-4, and allogeneic chimerism rates were detected. The survival time of the transgenic imDC group (27.5 ± 7.55 days) was significantly longer than in the other three groups (P < 0.01). The GVHD score of the imDC group mice was significantly lower than in the transplantation and empty vector groups (P < 0.05), which meant that mice in the transgenic imDC group had the lightest pathology damage in the target organs. In the transplantation group, IFN-γ increased while IL-4 decreased. In contrast, IFN-γ decreased and IL-4 increased in both empty vector and trans-imDC groups, and the difference was significant in the latter (P < 0.01). Thirty days or more following transplantation, the allogeneic chimerism rate was still 95-100%, suggesting complete donor type implantation. Ccr7 transfection into imDCs suppressed occurrence and severity of acute GVHD after allo-BMT in mice; the mechanism might be associated with IFN-γ decrease and IL-4 increase.


Assuntos
Transplante de Medula Óssea , Células Dendríticas/imunologia , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/terapia , Animais , Movimento Celular , Proliferação de Células , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/patologia , Interferon gama/sangue , Interleucina-4/sangue , Lentivirus , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Especificidade de Órgãos , Análise de Sobrevida , Linfócitos T/citologia , Transplante Homólogo
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