A NONDELETIONAL MECHANISM OF PERIPHERAL TOLERANCE IN T-CELL RECEPTOR TRANSGENIC MICE
- Author(s)
- Morahan, G; Hoffmann, MW; Miller, JFAP;
- Details
- Publication Year 1991-12,Volume 88,Issue #24,Page 11421-11425
- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- Publication Type
- Journal Article
- Abstract
- To investigate tolerance to extrathymic self molecules, we produced two groups of transgenic mice: one expressed the major histocompatibility complex molecule H-2K(b) in pancreatic beta-cells, and the other expressed rearranged T-cell receptor genes encoding an anti-H-2K(b) receptor. The transgenic T-cell receptor genes were shown to confer the correct specificity and to be expressed appropriately. T cells bearing this receptor were activated by H-2K(b) in vitro and in vivo, and they underwent negative selection in mice expressing H-2K(b) in the thymus. To determine the fate and function of these anti-H-2K(b) T cells in mice expressing H-2K(b) exclusively in the periphery, the two groups of transgenic mice were mated to produce double transgenic offspring. In these, transgene-expressing T cells were present in both thymus and periphery. Persisting T cells had not down-regulated either their antigen-specific receptors or their CD8 molecules. Despite the persistence of large numbers of potentially reactive T cells, the mice were tolerant of H-2K(b) in that they could not reject H-2K(b)-bearing skin grafts, although they did reject third-party grafts. The results show that peripheral T-cell tolerance, unlike that imposed in the thymus, does not involve deletion of T cells. The existence of T cells bearing receptors specific for self components raises the possibility that aberrant activation of such cells may lead to the development of autoimmune disease.
- Publisher
- NATL ACAD SCIENCES
- Keywords
- CLASS-II MHC; PANCREATIC BETA-CELLS; ANTIGEN RECEPTOR; EXPRESSION; MOLECULES; DELETION; REARRANGEMENT; INACTIVATION; SELECTION; GENES
- Publisher's Version
- https://doi.org/10.1073/pnas.88.24.11421
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 1991-12-01 12:00:00