Intrathymic deletion of MHC class I-restricted cytotoxic T cell precursors by constitutive cross-presentation of exogenous antigen.
Cross-priming of cytotoxic T lymphocytes by professional antigen-presenting cells (APC) is a potential hazard to self tolerance because it exposes naive T cells to tissue-specific self antigens in the context of co-stimulatory signals. Here we show that cross-presentation of exogenous material occurs constitutively within the thymus. Although efficient cross-presentation is a property of relatively few APC it results in thymocyte deletion both in vitro and in vivo, suggesting that intrathymic cross-presentation can operate as an effective component of tolerance to circulating self antigens. The capacity of minor cell populations to mediate thymocyte deletion but not positive selection reflects an underlying difference in the biology of these two processes.
Merkenschlager
M
M
Lymphocyte Development Group, MRC Clinical Sciences Centre, London, Great Britain. mmerkens@rpms.ac.uk
Power
M O
MO
Pircher
H
H
Fisher
A G
AG
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000276:immunology; D004705:Endocytosis; D004847:Epithelial Cells / Q000276:immunology; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017154:Stromal Cells / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D018528:ATP-Binding Cassette Transporters; D015395:Histocompatibility Antigens Class I; C073119:TAP1 protein, human; C486171:Tap1 protein, mouse