Selection of Foxp3+ regulatory T cells specific for self antigen expressed and presented by Aire+ medullary thymic epithelial cells.
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.
Aschenbrenner
Katharina
K
Research Institute of Molecular Pathology, 1030 Vienna, Austria.
D'Cruz
Louise M
LM
Vollmann
Elisabeth H
EH
Hinterberger
Maria
M
Emmerich
Jan
J
Swee
Lee Kim
LK
Rolink
Antonius
A
Klein
Ludger
L
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004847:Epithelial Cells / Q000276:immunology; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology*; D006388:Hemagglutinins / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D017634:Self Tolerance / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology*; D000096927:AIRE Protein
D001324:Autoantigens; D051858:Forkhead Transcription Factors; D006388:Hemagglutinins; D000949:Histocompatibility Antigens Class II; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors; D000096927:AIRE Protein; C498833:Foxp3 protein, mouse