Thymus-blood protein interactions are highly effective in negative selection and regulatory T cell induction

J Immunol. 2009 Dec 15;183(12):7909-18. doi: 10.4049/jimmunol.0902632.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigen Presentation / genetics
  • Antigen Presentation / immunology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Chickens
  • Clone Cells
  • Dendritic Cells / enzymology
  • Dendritic Cells / immunology
  • Down-Regulation / genetics
  • Down-Regulation / immunology*
  • Female
  • Growth Inhibitors / antagonists & inhibitors
  • Growth Inhibitors / blood
  • Growth Inhibitors / metabolism*
  • Hybridomas
  • Immune Tolerance / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Muramidase / antagonists & inhibitors
  • Muramidase / blood
  • Muramidase / metabolism*
  • Ovalbumin / antagonists & inhibitors
  • Ovalbumin / blood
  • Ovalbumin / immunology
  • Receptors, Antigen, T-Cell / blood
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / metabolism
  • Spleen / cytology
  • Spleen / enzymology
  • Spleen / immunology
  • T-Lymphocytes, Regulatory / cytology*
  • T-Lymphocytes, Regulatory / enzymology
  • T-Lymphocytes, Regulatory / immunology*
  • Thymus Gland / cytology*
  • Thymus Gland / enzymology
  • Thymus Gland / immunology*
  • Up-Regulation / genetics
  • Up-Regulation / immunology

Substances

  • Growth Inhibitors
  • Receptors, Antigen, T-Cell
  • Ovalbumin
  • hen egg lysozyme (48-62)
  • Muramidase