Article abstract
Nature Immunology 8, 351 - 358 (2007)
Published online: 25 February 2007 | doi:10.1038/ni1444
Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells
Katharina Aschenbrenner1, Louise M D'Cruz1,3, Elisabeth H Vollmann1,3, Maria Hinterberger1, Jan Emmerich1, Lee Kim Swee2, Antonius Rolink2 & Ludger Klein1
Abstract
The parameters specifying whether autoreactive CD4+ thymocytes are deleted (recessive tolerance) or differentiate into regulatory T cells (dominant tolerance) remain unresolved. Dendritic cells directly delete thymocytes, partly through cross-presentation of peripheral antigens 'promiscuously' expressed in medullary thymic epithelial cells (mTECs) positive for the autoimmune regulator Aire. It is unclear if and how mTECs themselves act as antigen-presenting cells during tolerance induction. Here we found that an absence of major histocompatibility class II molecules on mTECs resulted in fewer polyclonal regulatory T cells. Furthermore, targeting of a model antigen to Aire+ mTECs led to the generation of specific regulatory T cells independently of antigen transfer to dendritic cells. Thus, 'routing' of mTEC-derived self antigens may determine whether specific thymocytes are deleted or enter the regulatory T cell lineage.
- Research Institute of Molecular Pathology, 1030 Vienna, Austria.
- Department of Clinical and Biological Sciences, Center for Biomedicine, University of Basel, CH-4051 Basel, Switzerland.
- Present addresses: Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093, USA (L.M.D.) and The CBR Institute for Biomedical Research, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA (E.H.V.).
Correspondence to: Ludger Klein1 e-mail: klein@imp.univie.ac.at
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