Cellular and Molecular Life Sciences

, 68:2873

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

Review

DOI: 10.1007/s00018-011-0730-6

Cite this article as:
Katz, J.D. & Janssen, E.M. Cell. Mol. Life Sci. (2011) 68: 2873. doi:10.1007/s00018-011-0730-6

Abstract

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.

Keywords

Type 1 diabetesNOD miceMerocytic dendritic cellsTolerance

Abbreviations

T1D

Type 1 diabetes

Ag

Antigen(s)

TCR

T cell receptor

APC

Antigen-presenting cell

DC

Dendritic cell(s)

FLT3

Fms-like tyrosine kinase 3

FLT3L

FLT3 ligand

mcDC

Merocytic dendritic cells

IKDC

Natural killer dendritic cells

Th1/Tc1

T helper cell type 1/T cytotoxic cell type 1

pDC

Plasmacytoid dendritic cells

cDC

Conventional dendritic cells

PLN

Pancreatic lymph nodes

CLP

Common lymphoid precursors

CMP

Common myeloid precursors

NOD

Non-obese diabetic

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