Galvani Rômulo G, Lemos Ramon, Areal Rômulo B, Salvador Pollyanna A, Zamboni Dario S, Wanderley João Luiz M, Bonomo Adriana
Divisão de Medicina Experimental, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; Departamento de Imunologia, Instituto de Microbiologia Professor Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Divisão de Medicina Experimental, Coordenação de Pesquisa, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
PLoS One. 2015 Feb 2;10(2):e0118079. doi: 10.1371/journal.pone.0118079. eCollection 2015.
Graft versus host disease (GVHD) is the major limitation of allogeneic hematopoietic stem cell transplantation (HSCT) presenting high mortality and morbidity rates. However, the exact cause of death is not completely understood and does not correlate with specific clinical and histological parameters of disease. Here we show, by using a semi-allogeneic mouse model of GVHD, that mortality and morbidity can be experimentally separated. We injected bone marrow-derived dendritic cells (BMDC) from NOD2/CARD15-deficient donors into semi-allogeneic irradiated chimaeras and observed that recipients were protected from death. However, no protection was observed regarding clinical or pathological scores up to 20 days after transplantation. Protection from death was associated with decreased bacterial translocation, faster hematologic recovery and epithelial integrity maintenance despite mononuclear infiltration at day 20 post-GVHD induction with no skew towards different T helper phenotypes. The protected mice recovered from aGVHD and progressively reached scores compatible with healthy animals. Altogether, our data indicate that severity and mortality can be separate events providing a model to study transplant-related mortality.
移植物抗宿主病（GVHD）是异基因造血干细胞移植（HSCT）的主要限制因素，其死亡率和发病率很高。然而，确切的死亡原因尚未完全明确，且与疾病的特定临床和组织学参数无关。在此，我们通过使用GVHD的半同种异体小鼠模型表明，死亡率和发病率在实验中可以分离。我们将来自NOD2/CARD15缺陷供体的骨髓源性树突状细胞（BMDC）注射到经半同种异体照射的嵌合体中，观察到受体受到了死亡保护。然而，在移植后长达20天的时间里，在临床或病理评分方面未观察到保护作用。免受死亡与细菌易位减少、血液学恢复加快以及上皮完整性维持有关，尽管在GVHD诱导后第20天存在单核细胞浸润，且未偏向不同的辅助性T细胞表型。受保护的小鼠从急性移植物抗宿主病中恢复过来，并逐渐达到与健康动物相符的评分。总之，我们的数据表明严重程度和死亡率可能是独立的事件，为研究移植相关死亡率提供了一个模型。
