Autoimmune diseases result from an aberrant response of the immune system that target self-tissues. Our understanding of normal immune development has been used to subvert this selfreactivity and involves exposing selfantigen to the developing immune system. This can be achieved through bone marrow derived cells, thus introducing potential clinical application. We have used the mouse model of multiple sclerosis to demonstrate that the transfer of bone marrow encoding a target autoantigen can be used to promote immune tolerance. The process of preconditioning recipients for hematopoietic stem cell transfer is critical for potential human translation. Thus, we have directly addressed if our model can also be applied in non-myeloablative and less toxic conditioning to promote tolerance and reverse established disease. Our studies to date indicate that this can indeed be achieved and that only low levels of chimerism are required to achieve tolerance.