Breaking T cell tolerance to beta cell antigens by merocytic dendritic cells



In type 1 diabetes (T1D), a break in central and peripheral tolerance results in antigen-specific T cells destroying insulin-producing, pancreatic beta cells. Herein, we discuss the critical sub-population of dendritic cells responsible for mediating both the cross-presentation of islet antigen to CD8+ T cells and the direct presentation of beta cell antigen to CD4+ T cells. These cells, termed merocytic dendritic cells (mcDC), are more numerous in non-obese diabetic (NOD), and antigen-loaded mcDC rescue CD8+ T cells from peripheral anergy and deletion, and stimulate islet-reactive CD4+ T cells. When purified from the pancreatic lymph nodes of overtly diabetic NOD mice, mcDC can break peripheral T cell tolerance to beta cell antigens in vivo and induce rapid onset T cell-mediated T1D in young NOD mouse. Thus, the mcDC subset appears to represent the long-sought critical antigen-presenting cell responsible for breaking peripheral tolerance to beta cell antigen in vivo.


Type 1 diabetes NOD mice Merocytic dendritic cells Tolerance 



Type 1 diabetes




T cell receptor


Antigen-presenting cell


Dendritic cell(s)


Fms-like tyrosine kinase 3


FLT3 ligand


Merocytic dendritic cells


Natural killer dendritic cells


T helper cell type 1/T cytotoxic cell type 1


Plasmacytoid dendritic cells


Conventional dendritic cells


Pancreatic lymph nodes


Common lymphoid precursors


Common myeloid precursors


Non-obese diabetic


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Copyright information

© Springer Basel AG 2011

Authors and Affiliations

  1. 1.Division of Endocrinology, Department of Pediatrics, Cincinnati Children’s Research FoundationUniversity of Cincinnati College of MedicineCincinnatiUSA
  2. 2.Division of Molecular Immunology, Department of Pediatrics, Cincinnati Children’s Research FoundationUniversity of Cincinnati College of MedicineCincinnatiUSA

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