PMID- 17660838 OWN - NLM STAT- MEDLINE DCOM- 20071024 LR - 20070919 IS - 0268-3369 (Print) IS - 0268-3369 (Linking) VI - 40 IP - 7 DP - 2007 Oct TI - Marrow graft rejection by repeated transfusions of allogeneic donor spleen cells. PG - 691-8 AB - Many hematological diseases require long-term transfusion support, which causes production of donor-reactive antibodies in sensitized recipients. Sensitized patients are at an increased risk for graft rejection when they undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). Here, we established a highly sensitized murine model to investigate the mechanism of donor graft rejection. After BALB/c mice were repeatedly transfused with allogeneic spleen cells from C57BL/6 mice, there was a significant increase in complement-dependent cytotoxicity in the serum of sensitized mice. For transplantation, 1 x 10(7) bone marrow cells (BMCs) from C57BL/6 mice were injected into lethally irradiated recipient BALB/c mice. Sensitized mice died between 12 and 15 days post-transplantation, while non-sensitized mice remained alive after 28 days. The hematopoietic recovery rate declined over time in sensitized recipients. The homing trace assay showed a rapid disappearance of donor BMCs in the spleen and bone marrow of sensitized recipients. In addition, the recipient cells and antibodies in the sensitized serum were capable of inducing high level of cell- and complement-mediated cytotoxicity to the donor graft. Our finding may explain the impaired hematopoietic stem cell homing and poor hematopoietic engraftment observed in highly sensitized allo-HSCT patients. FAU - Xu, L H AU - Xu LH AD - Department of Pediatrics, Second Affiliated Hospital of Zhongshan University, Guangzhou, PR China. FAU - Fang, J P AU - Fang JP FAU - Huang, W G AU - Huang WG FAU - Xu, H G AU - Xu HG FAU - Weng, W J AU - Weng WJ FAU - Kao, G S AU - Kao GS FAU - Le, Y AU - Le Y LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20070730 PL - England TA - Bone Marrow Transplant JT - Bone marrow transplantation JID - 8702459 RN - 0 (Isoantibodies) SB - IM MH - Animals MH - Bone Marrow Transplantation/*immunology/mortality MH - Cell Transplantation/*adverse effects MH - Graft Rejection/*etiology MH - Humans MH - Isoantibodies/blood MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Mice, Inbred C57BL MH - Models, Animal MH - Spleen/*cytology MH - Tissue Donors MH - Transplantation, Homologous EDAT- 2007/07/31 09:00 MHDA- 2007/10/25 09:00 CRDT- 2007/07/31 09:00 PHST- 2007/07/31 09:00 [pubmed] PHST- 2007/10/25 09:00 [medline] PHST- 2007/07/31 09:00 [entrez] AID - 1705791 [pii] AID - 10.1038/sj.bmt.1705791 [doi] PST - ppublish SO - Bone Marrow Transplant. 2007 Oct;40(7):691-8. doi: 10.1038/sj.bmt.1705791. Epub 2007 Jul 30.