Dissociation of thymic positive and negative selection in transgenic mice expressing major histocompatibility complex class I molecules exclusively on thymic cortical epithelial cells.

Details

Serval ID
serval:BIB_824B26D36FB8
Type
Article: article from journal or magazin.
Collection
Publications
Title
Dissociation of thymic positive and negative selection in transgenic mice expressing major histocompatibility complex class I molecules exclusively on thymic cortical epithelial cells.
Journal
Blood
Author(s)
Capone M., Romagnoli P., Beermann F., MacDonald H.R., van Meerwijk J.P.
ISSN
0006-4971
Publication state
Published
Issued date
2001
Peer-reviewed
Oui
Volume
97
Number
5
Pages
1336-1342
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Thymic positive and negative selection of developing T lymphocytes confronts us with a paradox: How can a T-cell antigen receptor (TCR)-major histocompatibility complex (MHC)/peptide interaction in the former process lead to transduction of signals allowing for cell survival and in the latter induce programmed cell death or a hyporesponsive state known as anergy? One of the hypotheses put forward states that the outcome of a TCR-MHC/peptide interaction depends on the cell type presenting the selecting ligand to the developing thymocyte. Here we describe the development and lack of self-tolerance of CD8(+) T lymphocytes in transgenic mice expressing MHC class I molecules in the thymus exclusively on cortical epithelial cells. Despite the absence of MHC class I expression on professional antigen-presenting cells, normal numbers of CD8(+) cells were observed in the periphery. Upon specific activation, transgenic CD8(+) T cells efficiently lysed syngeneic MHC class I(+) targets in vitro and in vivo, indicating that thymic cortical epithelium (in contrast to medullary epithelium and antigen-presenting cells of hematopoietic origin) is incapable of tolerance induction. Thus, compartmentalization of the antigen-presenting cells involved in thymic positive selection and tolerance induction can (at least in part) explain the positive/negative selection paradox.
Keywords
Animals, Autoantigens/immunology, CD8-Positive T-Lymphocytes/metabolism, Cytotoxicity Tests, Immunologic, Epithelial Cells/immunology, Epithelial Cells/metabolism, Histocompatibility Antigens Class I/immunology, Histocompatibility Antigens Class I/metabolism, Humans, Keratin-14, Keratins/genetics, Mice, Mice, Mutant Strains, Mice, Transgenic/immunology, Promoter Regions, Genetic, Selection, Genetic, Thymus Gland/cytology, beta 2-Microglobulin/genetics
Pubmed
Web of science
Open Access
Yes
Create date
11/02/2010 11:17
Last modification date
08/05/2019 21:12
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