title: Breaking T cell tolerance to beta cell antigens by merocytic dendritic cells.
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.
authors.affiliation: Division of Endocrinology, Department of Pediatrics, Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA. jonathan.katz@cchmc.org
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Katz
authors.forename: Edith M
authors.initials: EM
authors.lastname: Janssen
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D007108:Immune Tolerance; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD