Cutting edge: merocytic dendritic cells break T cell tolerance to beta cell antigens in nonobese diabetic mouse diabetes.

Jonathan D. Katz, Jennifer K. Ondr, Robert Opoka, Zacharias Garcia, Edith M. Janssen

Research output: Contribution to journalArticle

Abstract

In type 1 diabetes, the breach of central and peripheral tolerance results in autoreactive T cells that destroy insulin-producing, pancreatic β cells. In this study, we identify a critical subpopulation of dendritic cells responsible for mediating both the cross-presentation of islet Ags to CD8+ T cells and the direct presentation of β cell Ags to CD4+ T cells. These cells, termed merocytic dendritic cells (mcDCs), are more numerous in the NOD mouse and, when Ag-loaded, rescue CD8+ T cells from peripheral anergy and deletion while stimulating islet-reactive CD4+ T cells. When purified from the pancreatic lymph nodes of overtly diabetic NOD mice, mcDCs break peripheral T cell tolerance to β cells in vivo and induce rapid onset type 1 diabetes in the young NOD mouse. Thus, the mcDC subset appears to represent the long-sought APC responsible for breaking peripheral tolerance to β cell Ags in vivo.

Original languageUndefined/Unknown
JournalPaediatrics and Child Health, East Africa
DOIs
Publication statusPublished - 15 Aug 2010

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