Thymus-blood protein interactions are highly effective in negative selection and regulatory T cell induction.
Using hen egg-white lysozyme, the effect of blood proteins on CD4 thymic cells was examined. A small fraction of i.v. injected hen egg-white lysozyme rapidly entered the thymus into the medulla. There it was captured and presented by dendritic cells (DCs) to thymocytes from two TCR transgenic mice, one directed to a dominant peptide and a second to a poorly displayed peptide, both presented by MHC class II molecules I-A(k). Presentation by DC led to negative selection and induction of regulatory T cells, independent of epithelial cells. Presentation took place at very low levels, less than 100 peptide-MHC complexes per DC. Such low levels could induce negative selection, but even lower levels could induce regulatory T cells. The anatomy of the thymus-blood barrier, the highly efficient presentation by DC, together with the high sensitivity of thymic T cells to peptide-MHC complexes, results in blood protein Ags having a profound effect on thymic T cells.
Atibalentja
Danielle F
DF
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
Byersdorfer
Craig A
CA
Unanue
Emil R
ER
D000818:Animals; D017951:Antigen Presentation / Q000235:genetics / Q000276:immunology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002645:Chickens; D002999:Clone Cells; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology*; D005260:Female; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D006825:Hybridomas; D007108:Immune Tolerance / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009113:Muramidase / Q000037:antagonists & inhibitors / Q000097:blood / Q000378:metabolism*; D010047:Ovalbumin / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000097:blood / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology* / Q000201:enzymology / Q000276:immunology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D006131:Growth Inhibitors; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin; C517688:hen egg lysozyme (48-62); D009113:Muramidase