MEDULLARY THYMIC EPITHELIAL-CELLS INDUCE TOLERANCE TO INTRACELLULAR PROTEINS

The role of the medullary thymic epithelial cells in tolerance inducti on to MHC class I restricted self peptides has been analyzed by studyi ng the beta-galactosidase (beta-gal)-specific cytotoxic T cell respons e of a transgenic mouse expressing beta-gal in the thymus, skin, and c entral nervous system (Tg beta-gal mouse), Our results showed that: 1) beta-gal expression in the thymus was limited in a subpopulation of m edullary epithelial cells, and bone marrow-derived thymic cells were b eta-gal(-); 2) Tg beta-gal mice did not mount an anti-beta-gal CTL res ponse even in the presence of exogenous IL-2, while Tg beta-gal-->B6 c himeras responded to beta-gal as strongly as NTg beta-gal mice; 3) Tg beta-gal mice did not generate CTL against the immunodominant K-b-rest ricted beta-gal 397-504 peptide; 4) tolerance was due to the thymic ep ithelial 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 K-b-restrided beta-gal 497-504 epitope, In conc lusion, these results demonstrate that medullary thymic epithelial cel ls induce a complete tolerance towards class I-restricted self peptide s presented on their own surface.