Breaking T cell tolerance to beta cell antigens by merocytic dendritic cells |
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Authors: | Jonathan D Katz Edith M Janssen |
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Affiliation: | (1) Division of Endocrinology, Department of Pediatrics, Cincinnati Children’s Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC 7021, Cincinnati, OH 45229-3039, USA;(2) Division of Molecular Immunology, Department of Pediatrics, Cincinnati Children’s Research Foundation, University of Cincinnati College of Medicine, 3333 Burnet Avenue, MLC 7021, Cincinnati, OH 45229-3039, USA |
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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. |
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