Open AccessElimination of insulitis and augmentation of islet β cell regeneration via induction of chimerism in overtly diabetic NOD mice
Author(s) -
Chunyan Zhang,
Ivan Todorov,
Chia-Lei Lin,
Mark A. Atkinson,
Fouad Kandeel,
Stephen J. Forman,
Defu Zeng
Publication year - 2007
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.0611101104
Subject(s) - insulitis , nod mice , nod , immunology , haematopoiesis , bone marrow , transplantation chimera , type 1 diabetes , regeneration (biology) , transplantation , islet , medicine , autoimmunity , cd8 , diabetes mellitus , biology , immune system , endocrinology , stem cell , hematopoietic cell , microbiology and biotechnology
Type 1 diabetes in both humans and nonobese diabetic (NOD) mice results from autoreactive T cell destruction of insulin-producing β cells. Cure of type 1 diabetes may require both reversal of autoimmunity and regeneration of β cells. Induction of chimerism via allogeneic hematopoietic cell transplantation has been shown to reestablish tolerance in both prediabetic and diabetic NOD mice. However, it is unclear whether this therapy augments β cell regeneration. Furthermore, this procedure usually requires total body irradiation conditioning of recipients. The toxicity of total body irradiation conditioning and potential for graft-versus-host disease (GVHD) limit the application of allogeneic hematopoietic cell transplantation for treating type 1 diabetes. Here we report that injection of donor bone marrow and CD4+ T cell-depleted spleen cells induced chimerism without causing GVHD in overtly diabetic NOD mice conditioned with anti-CD3/CD8 and that induction of chimerism in new-onset diabetic NOD mice led to elimination of insulitis, regeneration of host β cells, and reversal of hyperglycemia. Therefore, this radiation-free GVHD preventive approach for induction of chimerism may represent a viable means for reversing type 1 diabetes.