Medullary thymic epithelial cells induce tolerance to intracellular proteins.
The role of the medullary thymic epithelial cells in tolerance induction to MHC class I restricted self peptides has been analyzed by studying the beta-galactosidase (beta-gal)-specific cytotoxic T cell response of a transgenic mouse expressing beta-gal in the thymus, skin, and central nervous system (Tg beta-gal mouse). Our results showed that: 1) beta-gal expression in the thymus was limited in a subpopulation of medullary epithelial cells, and bone marrow-derived thymic cells were beta-gal-1; 2) Tg beta-gal mice did not mount an anti-beta-gal CTL response even in the presence of exogenous IL-2, while Tg beta-gal-->B6 chimeras responded to beta-gal as strongly as NTg beta-gal mice; 3) Tg beta-gal mice did not generate CTL against the immunodominant Kb-restricted beta-gal 497-504 peptide; 4) tolerance was due to the thymic epithelial cells that expressed beta-gal because nude mice grafted with thymus from Tg beta-gal mice were also unable to respond to beta-gal; 5) the Tg beta-gal mouse-derived beta-gal+ medullary epithelial TEC.X10 line presented the Kb-restricted beta-gal 497-504 epitope. In conclusion, these results demonstrate that medullary thymic epithelial cells induce a complete tolerance towards class I-restricted self peptides presented on their own surface.
Oukka
M
M
INSERM Unit 267, Paul Brousse Hospital, Villejuif, France.
Cohen-Tannoudji
M
M
Tanaka
Y
Y
Babinet
C
C
Kosmatopoulos
K
K
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000235:genetics; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D006183:H-2 Antigens / Q000235:genetics; D007108:Immune Tolerance; D007424:Intracellular Fluid / Q000201:enzymology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D001616:beta-Galactosidase / Q000235:genetics / Q000276:immunology
D000939:Epitopes; D006183:H-2 Antigens; D001616:beta-Galactosidase