A TRANSGENIC WINDOW ON PERIPHERAL T-CELL TOLERANCE
- Author(s)
- Miller, JFAP;
- Journal Title
- IMMUNOLOGY AND CELL BIOLOGY
- Publication Type
- Journal Article
- Abstract
- There is convincing evidence for the imposition of self-tolerance by means of the clonal deletion of self-reactive T cells within the thymus. Since not all self components may be encountered there, the question must be asked whether tolerance can occur post-thymically. To test this, we have used transgenic technology to direct expression of a 'non-self gene, H-2K(b), to the insulin-producing beta-cells of the pancreas in mice. These 'RIP-K(b)' transgenic mice were specifically tolerant of H-2K(b)-bearing skin grafts. To test the fate of potentially reactive H-2K(b)-specific T cells in these tolerant mice, the RIP-K(b) mice were mated to a second series of transgenic mice with rearranged T cell receptor (TCR) genes encoding an H-2K(b)-specific TCR to produce' double transgenic' offspring. The TCR was detectable by a clonotype-specific antibody. Although there was some evidence of intrathymic deletion of those T cells that expressed the highest density of the H-2K(b)-specific TCR, lower density cells were present in the periphery. These may have been either indifferent to the H-2K(b) molecule expressed on the beta-cells or functionally silenced by it. Further experiments are planned to determine which of these two situations exists.
- Publisher
- BLACKWELL SCIENCE
- Keywords
- MICE; MECHANISM; ANTIGENS
- Publisher's Version
- https://doi.org/10.1038/icb.1992.7
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1992-02-01 12:00:00