TY - JOUR
T1 - Thymus-blood protein interactions are highly effective in negative selection and regulatory T cell induction
AU - Atibalentja, Danielle F.
AU - Byersdorfer, Craig A.
AU - Unanue, Emil R.
PY - 2009/12/15
Y1 - 2009/12/15
N2 - 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-Ak. 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.
AB - 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-Ak. 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.
UR - http://www.scopus.com/inward/record.url?scp=76249088374&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.0902632
DO - 10.4049/jimmunol.0902632
M3 - Article
C2 - 19933868
AN - SCOPUS:76249088374
VL - 183
SP - 7909
EP - 7918
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -