Down-regulation of T cell receptors on self-reactive T cells as a novel mechanism for extrathymic tolerance induction.
By generating two types of transgenic mice we have investigated how extrathymic events can contribute to self tolerance. The major histocompatibility complex class I gene Kb was expressed under the control of the glial fibrillary acidic protein promoter in cells of neuroectodermal origin outside the thymus. These mice were tolerant to Kb. When crossed to transgenic mice expressing a Kb-specific T cell receptor (TCR), clonotype+, CD8+CD4- mature T cells could be detected in normal numbers in the thymus of the double-transgenic mice but were strongly reduced in spleen and lymph nodes in comparison with TCR single-transgenic mice. After isolation of clonotype negative splenic T cells and activation in vitro, reappearance of the clonotype+, CD8+CD4- cells was observed. These results indicate that down-regulation of TCR and CD8 molecules on the antigen-specific T cells is a novel mechanism, by which peripheral tolerance to this antigen can occur.
Schönrich
G
G
Institute of Immunology and Genetics, German Cancer Research Center, Heidelberg.
Kalinke
U
U
Momburg
F
F
Malissen
M
M
Schmitt-Verhulst
A M
AM
Malissen
B
B
Hämmerling
G J
GJ
Arnold
B
B
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics; D017252:CD3 Complex; D015536:Down-Regulation; D005260:Female; D015332:Gene Rearrangement, alpha-Chain T-Cell Antigen Receptor; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D005805:Genes, MHC Class I; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics*; D006085:Graft Survival; D006239:Haplotypes; D007108:Immune Tolerance / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016038:Skin Transplantation / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D005904:Glial Fibrillary Acidic Protein; D011948:Receptors, Antigen, T-Cell