Induction of Mixed Chimerism for Reversal of Autoimmunity in Type 1 Diabetes
نویسندگان
چکیده
Type 1 diabetes (T1D) results from autoimmune attack of insulin-producing pancreatic islet β cells. T1D autoimmunity is associated with particular MHC or HLA types in mouse or humans. T1D autoimmunity arises from defects in both central negative selection and peripheral regulation of autoreactive T cells as well as intrinsic defects of B cells. Current therapies that target at improving peripheral tolerance of autoreactive T cells or depleting B cells have not yielded significant therapeutic effects in reversal of autoimmunity in T1D patients. Induction of mixed chimerism with bone marrow cells from non-autoimmune donors has been recently indicated to be a curative therapy for reversal of autoimmunity in T1D. In this review, we have summarized and discussed T1D related abnormalities in the hematopoietic compartment, regimens that induce mixed chimerism in the T1D animal model of non-obese diabetic (NOD) mice, and how mixed chimerism corrects central negative selection and peripheral tolerance of autoreactive T and B cells. Induction of Mixed Chimerism for Reversal of Autoimmunity in Type 1 Diabetes
منابع مشابه
Mixed hematopoietic chimerism allows cure of autoimmune diabetes through allogeneic tolerance and reversal of autoimmunity.
Bone marrow transplantation from diabetes-resistant strains with complete replacement of the recipient immune system by the allogeneic donor has led to tolerance to donor islets and cure of diabetes in a mouse model of type 1 diabetes. However, the ability to tolerize host T-cells of diabetic NOD mice is unknown. We demonstrate that nonmyeloablative conditioning achieves mixed hematopoietic chi...
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Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system with demyelination, axon damage, and paralysis. Induction of mixed chimerism with allogeneic donors has been shown to not cause graft-versus-host disease (GVHD) in animal models and humans. We have reported that induction of MHC-mismatched mixed chimerism can cure autoimmunity in autoimmune NOD mice, but...
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OBJECTIVE Induction of mixed or complete chimerism via hematopoietic cell transplantation (HCT) from nonautoimmune donors could prevent or reverse type 1 diabetes (T1D). In clinical settings, HLA-matched HCT is preferred to facilitate engraftment and reduce the risk for graft versus host disease (GVHD). Yet autoimmune T1D susceptibility is associated with certain HLA types. Therefore, we tested...
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Autoimmune type 1 diabetes (T1D) and other autoimmune diseases are associated with particular MHC haplotypes and expansion of autoreactive T cells. Induction of MHC-mismatched but not -matched mixed chimerism by hematopoietic cell transplantation effectively reverses autoimmunity in diabetic nonobese diabetic (NOD) mice, even those with established diabetes. As expected, MHC-mismatched mixed ch...
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The mechanism by which mixed chimerism reverses autoimmunity in type 1 diabetes has not been defined. NOD mice have a well-characterized defect in the production of myeloid progenitors that is believed to contribute significantly to the autoimmune process. We therefore investigated whether chimerism induces a correction of this defect. Mixed chimerism restored production of myeloid progenitors ...
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