Successful prevention of autoimmune disease by transplantation of adequatenumber of fully allogeneic hematopoietic stem cells

Background. We have previously shown successful engraftment of allogeneic h ematopoietic stem cells (HSCs) when transplanted across the major histocomp atibility antigen barriers if transplanted along with a preparation of faci litator cells (osteoblasts). We have investigated whether or not fully allo geneic HSCs from healthy mouse donors prevent the development of autoimmuni ties in the autoimmune-prone W/B F1 mice. Methods. W/B F1 is a strain of mice that spontaneously develop autoimmuniti es, a coronary vascular disease, thrombocytopenia, and systemic lupus-like syndrome. The 6- to 8-week-old (before the onset of the disease) W/B F1 mic e have been transplanted with either a preparation of HSCs alone, or along with facilitator cells from MHC-incompatible autoimmune-resist ant BALB/c m ice, then followed to determine longterm survival and whether or not they d eveloped signs of the autoimmune disease. Results. The number of the transplanted HSCs acts as the determining factor in achieving successful and durable engraftment, Survival of the W/B F1 mi ce significantly improved by transplantation of increasing numbers of HSCs, either alone or along with facilitator cells, When W/B F1 mice were transp lanted with 2-5 million HSCs, more than 1-year survival was 100%, all the t ransplanted mice were fully engrafted with allogeneic HSCs, and were free o f signs of the autoimmune disease. Histological sections of the hearts, lun gs, and kidneys of the transplanted mice showed absence of the autoimmune-a ssociated pathology. Conclusions. We thus report herein the successful prevention of autoimmune disease by transplantation of a sufficiently large number of purified fully allogeneic HSCs in W/B F1 mice.