在小鼠骨髓移植中CCR5与急性移植物抗宿主病的相关性研究论文.docVIP

　　在小鼠骨髓移植中CCR5与急性移植物抗宿主病的相关性研究论文 【摘要】 本研究评价供者CCR5在经过强化预处理的骨髓移植动物模型受者体内的作用，为今后的异基因造血干细胞移植的临床应用提供科学依据。经过致死剂量照射的BALB/c小鼠接受异基因C57BL/6小鼠的骨髓移植。根据回输的细胞不同实验分为4组：B6 CCR5 KO组，受者接受C57BL/6 CCR5-/-小鼠骨髓和脾脏细胞；B6 C组，受者只接受C57BL/6 CCR5-/-小鼠骨髓细胞；B6 C组，受者只接受野生型C57BL/6小鼠骨髓细胞。结果表明：较之B6 T as selves), recruit other cells in the generation of organ damage［1,2］.This in part is the“cytokine storm” that fuels GVHD pathogenesis［3］. Multiple organs are affected in acute GVHD including the skin, gut, lungs, and liver. T contributes to the generation and pathology of GVHD in both man and mouse［4,5］, emphasizing the importance of models that can reflect the conditioning regimens used in clinical BMT. Chemokines are a diverse group of cytokines that modulate immune cell trafficking and function［6,7］. Due to the properties of chemokines,.freelokines may play a role in GVHD. Serody et al［8］ demonstrated reduced lethality in recipients of donor T cells from MIP-1α-deficient mice pared to ediated GVHD model. Recent reports also indicated that blockade of CCR5 using neutralizing antibodies could also protect from GVHD using a parent into F1 GVHD model［9］. This report and another using CCR5 KO mice in the same model indicated that CCR5 on cells played a role in augmenting the GVHD response and that blockade of this interaction could be used to prevent GVHD［9,10］. Hoechanism underlying this protection ay play a role in doe infectious disease models［11］, suggesting that this receptor-ligand interaction may exert diverse effects. The previous reports assessing the role of CCR5 expression on GVHD used a model in inistered. Chemokine production as arkedly influenced by inflammatory cytokines induced after total-body irradiation (TBI)［12,13］. T. Our results demonstrate that the absence of CCR5 on donor cells results in a significant increase in GVHD morbidity that the Animal Production Area (NCI at Frederick,Frederick,MD,USA). C57BL/6 CCR5-/- mice (B6 CCR5 KO) t Kuziel. All recipients atched females and onths