Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 6272K) PDF+supp data (11422K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ohnmacht, C. Articles by Voehringer, D. Search for Related Content PubMed PubMed Citation Articles by Ohnmacht, C. Articles by Voehringer, D. Related Collections Related Article Social Bookmarking                            What's this?

¹ Institute for Immunology, Department of Medicine, University of Munich, 80336 Munich, Germany
² Institute of Molecular Virology, Antigen-specific Immunotherapy Clinical Cooperation Group, National Research Center for Environment and Health and Technische Universität München, 81675 Munich, Germany

CORRESPONDENCE David Voehringer: david.voehringer{at}med.uni-muenchen.de

Lack of immunological tolerance against self-antigens results in autoimmune disorders. During onset of autoimmunity, dendritic cells (DCs) are thought to be critical for priming of self-reactive T cells that have escaped tolerance induction. However, because DCs can also induce T cell tolerance, it remains unclear whether DCs are required under steady-state conditions to prevent autoimmunity. To address this question, we crossed CD11c-Cre mice with mice that express diphtheria toxin A (DTA) under the control of a loxP-flanked neomycin resistance (neo^R) cassette from the ROSA26 locus. Cre-mediated removal of the neo^R cassette leads to DTA expression and constitutive loss of conventional DCs, plasmacytoid DCs, and Langerhans cells. These DC-depleted (DC) mice showed increased frequencies of CD4 single-positive thymocytes and infiltration of CD4 T cells into peripheral tissues. They developed spontaneous autoimmunity characterized by reduced body weight, splenomegaly, autoantibody formation, neutrophilia, high numbers of Th1 and Th17 cells, and inflammatory bowel disease. Pathology could be induced by reconstitution of wild-type (WT) mice with bone marrow (BM) from DC mice, whereas mixed BM chimeras that received BM from DC and WT mice remained healthy. This demonstrates that DCs play an essential role to protect against fatal autoimmunity under steady-state conditions.

© 2009 Ohnmacht et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Related Article

Dendritic cells teach tolerance

Amy Maxmen
J. Exp. Med. 2009 206: 492. [Full Text] [PDF]

This article has been cited by other articles:

• St. Rose, M.-C., Qui, H. Z., Bandyopadhyay, S., Mihalyo, M. A., Hagymasi, A. T., Clark, R. B., Adler, A. J. (2009). The E3 Ubiquitin Ligase Cbl-b Regulates Expansion but Not Functional Activity of Self-Reactive CD4 T Cells. J. Immunol. 183: 4975-4983 [Abstract] [Full Text]  
• Darrasse-Jeze, G., Deroubaix, S., Mouquet, H., Victora, G. D., Eisenreich, T., Yao, K.-h., Masilamani, R. F., Dustin, M. L., Rudensky, A., Liu, K., Nussenzweig, M. C. (2009). Feedback control of regulatory T cell homeostasis by dendritic cells in vivo. JEM 206: 1853-1862 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS