A partial conditioning approach to achieve mixed chimerism in the rat: depletion of host natural killer cells significantly reduces the amount of total body irradiation required for engraftment.

摘要: Background Mixed allogeneic bone marrow chimerism induces tolerance to solid organ grafts. Although we previously reported that partially ablative conditioning with 700 cGy of total body irradiation (TBI) is sufficient allow for engraftment in mice, determined a minimum 1000 was required the rat. Because T cells and NK are critical graft rejection, our purpose examine whether targeting radioresistant and/or recipient hematopoietic microenvironment would reduce TBI dose rat marrow. Methods. Wistar Furth rats received either anti-NK3.2.3 monoclonal antibodies on days -3 -2, antilymphocyte serum day -5, combination both or no pretreatment. performed 0 were reconstituted 100×10 6 cell-depleted from ACI donors. Results. Engraftment readily achieved animals conditioned alone (12/12) level donor averaged 89%. At 900 only one eight recipients engrafted. In striking contrast, 11 12 pretreated anti-NK irradiated showed at mean 41%. No further enhancement could be when plus antibodies. chimeras exhibited stable multilineage donor-specific subsequent cardiac allografts. Conclusion. Specific host allows significant reduction engraftment.