Relationship between CCR5 and acute graft-versus-host disease in murine bone marrow transplantation.
- Author:
Zhao WANG
1
;
William J MURPHY
Author Information
1. Department of Hematology, Beijing Friendship Hospital, Capital University of Medicine Science, China. zhaowww263@yahoo.com
- Publication Type:Journal Article
- MeSH:
Animals;
Bone Marrow Transplantation;
adverse effects;
CD8-Positive T-Lymphocytes;
cytology;
immunology;
transplantation;
Female;
Graft vs Host Disease;
metabolism;
Mice;
Mice, Inbred BALB C;
Mice, Inbred C57BL;
Receptors, CCR5;
genetics;
physiology
- From:
Journal of Experimental Hematology
2006;14(5):934-940
- CountryChina
- Language:English
-
Abstract:
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.
