Abstract: Objective To evaluate the role of gene CCR5 on donor cells in models where intensive preconditioning of the recipient occurs,thus provide the scientific evidence for clinical experience of allo-HSCT.Methods Lethally irradiated BALB/C mice received C57BL/6 mice is allogeneic bone marrow transplants.We divided mice 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.Results Compared to B6 WT 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 vs WT control cells.T cells recovered from recipients of CCR5 KO cells roduced more IFN-γ and TNF-Αand proliferated to a T-cell mitogen at a significantly greater 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 kidney and a greater degree of liver pathological changes in mice that received CCR5 KO donor grafts.Conclusion The absence of gene CCR5 on donor cells results in increased GVHD and donor CD8⁺ T cells as well as hepatic and renal lesions in allo-HSCT,which indicated gene CCR5 is very important in allo-BMT.

Key words: CCR5, GVHD, allo-HSCT, CD8⁺ T-cell