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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jonathan D KatzEdith M Janssen

Abstract

In type 1 diabetes, the breach of central and peripheral tolerance results in autoreactive T cells that destroy insulin-producing, pancreatic beta 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 beta 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 beta 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 beta cell Ags in vivo.

References

Mar 19, 1996·Proceedings of the National Academy of Sciences of the United States of America·I AndréD Mathis
Jan 7, 1997·Proceedings of the National Academy of Sciences of the United States of America·M O KurrerJ D Katz
Aug 17, 1999·Journal of Leukocyte Biology·P A MorelM Feili-Hariri
Dec 14, 2001·Nature·D MathisC Benoist
May 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Raymond J SteptoeLeonard C Harrison
Jun 1, 2002·International Immunology·Simon J Prasad, Christopher C Goodnow
Oct 23, 2002·The Journal of Experimental Medicine·Gabrielle T BelzWilliam R Heath
Oct 4, 2003·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Benjamin D EhstMarc K Jenkins
Nov 19, 2003·The Journal of Experimental Medicine·Shannon TurleyDiane Mathis
Mar 30, 2004·European Journal of Immunology·Anja RoosCees van Kooten
Mar 18, 2005·Annual Review of Immunology·Mark S Anderson, Jeffrey A Bluestone
May 17, 2005·Nature Immunology·Zhengfan JiangBruce Beutler
Jun 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gabrielle T BelzWilliam R Heath
Oct 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vijay SaxenaJonathan D Katz
Aug 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Qing LiHugh O McDevitt

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Citations

Jun 1, 2011·Cellular and Molecular Life Sciences : CMLS·Jonathan D Katz, Edith M Janssen
Feb 14, 2012·Proceedings of the National Academy of Sciences of the United States of America·Martin A KriegelRichard A Flavell
Jan 1, 2012·The Review of Diabetic Studies : RDS·Kate L GrahamThomas W H Kay
Apr 29, 2016·Mediators of Inflammation·Jared KlarquistEdith M Janssen
Dec 25, 2012·Oncoimmunology·Jared S Klarquist, Edith M Janssen
Mar 8, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cindy AudigerSylvie Lesage
May 14, 2018·Immunology and Cell Biology·Cindy Audiger, Sylvie Lesage
May 29, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cindy AudigerSylvie Lesage
Jan 23, 2016·Journal of Leukocyte Biology·Chie Hotta-Iwamura, Kristin V Tarbell
Aug 8, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Claire A ChougnetEdith M Janssen
Apr 18, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Na YinJonathan S Bromberg
Nov 12, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jared KlarquistEdith M Janssen
Sep 1, 2018·Frontiers in Immunology·Charles J KrogerRoland M Tisch
Sep 6, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cindy Audiger, Sylvie Lesage

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