TY - JOUR
T1 - Relationship between CCR5 and acute graft-versus-host disease in murine bone marrow transplantation
AU - Wang, Zhao
AU - Murphy, William J
PY - 2006/10
Y1 - 2006/10
N2 - This study was aimed to eveluate the role of CCR5 on donor cells in recipient models received intensive conditioning, so as provide the scientific evidence for clinical application of allo-HSCT. Lethally irradiated BALB/c mice received allogeneic bone marrow transplants from C57BL/6 mice. Mice divided into 4 groups according to receiving variant donor cells: B6 CCR5 KO group, receiving C57BL/6 CCR5(-/-) mice bone marrow cells and splenocytes; B6 WT BMC group, receiving C57BL/6 mice bone marrow cells and splenocytes; B6 CCR5 KO BMC group, receiving C57BL/6 CCR5(-/-) bone marrow cells alone; B6 WT BMC group, receiving C57BL/6 mice bone marrow cells alone. The result showed that compared to B6 WT BMC group, B6 CCR5 KO group succumbed to acute GVHD at an accelerated rate. Donor CD8(+) T cells expanded to a significantly greater extent in recipients of CCR5 KO, compared with B6 WT control cells. T cells recovered from recipients of CCR5 KO cells produced more IFN-gamma and TNF-alpha and proliferated to a T-cell at a significantly higher level than T cells from recipients of WT cells, indicating that CCR5 plays a role in downregualting donor alloreative CD8(+) T-cells expansion. Histological assessment of the mice indicated pathological lesions in the kidneys and a greater degree of liver pathological changes in mice that received CCR5 KO donor grafts. It is concluded that the knock-out of CCR5 on donor cells results in increase of GVHD and donor CD8(+) T cell expansion, as well as hepatic and renal lesions in allo-HSCT, which indicates that CCR5 is very important in allo-BMT.
AB - This study was aimed to eveluate the role of CCR5 on donor cells in recipient models received intensive conditioning, so as provide the scientific evidence for clinical application of allo-HSCT. Lethally irradiated BALB/c mice received allogeneic bone marrow transplants from C57BL/6 mice. Mice divided into 4 groups according to receiving variant donor cells: B6 CCR5 KO group, receiving C57BL/6 CCR5(-/-) mice bone marrow cells and splenocytes; B6 WT BMC group, receiving C57BL/6 mice bone marrow cells and splenocytes; B6 CCR5 KO BMC group, receiving C57BL/6 CCR5(-/-) bone marrow cells alone; B6 WT BMC group, receiving C57BL/6 mice bone marrow cells alone. The result showed that compared to B6 WT BMC group, B6 CCR5 KO group succumbed to acute GVHD at an accelerated rate. Donor CD8(+) T cells expanded to a significantly greater extent in recipients of CCR5 KO, compared with B6 WT control cells. T cells recovered from recipients of CCR5 KO cells produced more IFN-gamma and TNF-alpha and proliferated to a T-cell at a significantly higher level than T cells from recipients of WT cells, indicating that CCR5 plays a role in downregualting donor alloreative CD8(+) T-cells expansion. Histological assessment of the mice indicated pathological lesions in the kidneys and a greater degree of liver pathological changes in mice that received CCR5 KO donor grafts. It is concluded that the knock-out of CCR5 on donor cells results in increase of GVHD and donor CD8(+) T cell expansion, as well as hepatic and renal lesions in allo-HSCT, which indicates that CCR5 is very important in allo-BMT.
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M3 - Article
C2 - 17096892
AN - SCOPUS:38049001598
VL - 14
SP - 934
EP - 940
JO - Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology
JF - Zhongguo shi yan xue ye xue za zhi / Zhongguo bing li sheng li xue hui = Journal of experimental hematology / Chinese Association of Pathophysiology
SN - 1009-2137
IS - 5
ER -