Mixed hematopoietic chimerism allows cure of autoimmune diabetes through allogeneic tolerance and reversal of autoimmunity.

Induction of Mixed Chimerism for Reversal of Autoimmunity in Type 1 Diabetes

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 periphe...

Allogeneic hematopoietic chimerism in mice treated with sublethal myeloablation and anti-CD154 antibody: absence of graft-versus-host disease, induction of skin allograft tolerance, and prevention of recurrent autoimmunity in islet-allografted NOD/Lt mice.

We describe a tolerance-based stem cell transplantation protocol that combines sublethal radiation with transient blockade of the CD40-CD154 costimulatory pathway using an anti-CD154 antibody. With this protocol, we established hematopoietic chimerism in BALB/c mice transplanted with fully allogeneic C57BL/6 bone marrow. The percentage of donor-origin mononuclear cells in recipients was more th...

MHC-mismatched mixed chimerism augments thymic regulatory T-cell production and prevents relapse of EAE in mice.

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...

Mixed Hematopoietic Chimerism Allows Cure of Autoimmune Glomerulonephritis: Its Potential and Risks

MHC-mismatched chimerism is required for induction of transplantation tolerance in autoimmune nonobese diabetic recipients.

In nonautoimmune recipients, induction of mixed and complete chimerism with hematopoietic progenitor cells from MHC (HLA)-matched or -mismatched donors are effective approaches for induction of organ transplantation immune tolerance in both animal models and patients. But it is still unclear whether this is the case in autoimmune recipients. With the autoimmune diabetic NOD mouse model, we repo...