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TSCOT+ thymic epithelial cell-mediated sensitive CD4 tolerance by direct presentation.

Authors :
Sejin Ahn
Gwanghee Lee
Soo Jung Yang
Deokjae Lee
Seunghyuk Lee
Hyo Sun Shin
Min Cheol Kim
Kee Nyung Lee
Douglas C Palmer
Marc R Theoret
Eric J Jenkinson
Graham Anderson
Nicholas P Restifo
Moon Gyo Kim
Source :
PLoS Biology, Vol 6, Iss 8, p e191 (2008)
Publication Year :
2008
Publisher :
Public Library of Science (PLoS), 2008.

Abstract

Although much effort has been directed at dissecting the mechanisms of central tolerance, the role of thymic stromal cells remains elusive. In order to further characterize this event, we developed a mouse model restricting LacZ to thymic stromal cotransporter (TSCOT)-expressing thymic stromal cells (TDLacZ). The thymus of this mouse contains approximately 4,300 TSCOT+ cells, each expressing several thousand molecules of the LacZ antigen. TSCOT+ cells express the cortical marker CDR1, CD40, CD80, CD54, and major histocompatibility complex class II (MHCII). When examining endogenous responses directed against LacZ, we observed significant tolerance. This was evidenced in a diverse T cell repertoire as measured by both a CD4 T cell proliferation assay and an antigen-specific antibody isotype analysis. This tolerance process was at least partially independent of Autoimmune Regulatory Element gene expression. When TDLacZ mice were crossed to a novel CD4 T cell receptor (TCR) transgenic reactive against LacZ (BgII), there was a complete deletion of double-positive thymocytes. Fetal thymic reaggregate culture of CD45- and UEA-depleted thymic stromal cells from TDLacZ and sorted TCR-bearing thymocytes excluded the possibility of cross presentation by thymic dendritic cells and medullary epithelial cells for the deletion. Overall, these results demonstrate that the introduction of a neoantigen into TSCOT-expressing cells can efficiently establish complete tolerance and suggest a possible application for the deletion of antigen-specific T cells by antigen introduction into TSCOT+ cells.

Subjects

Subjects :
Biology (General)
QH301-705.5

Details

Language :
English
ISSN :
15449173 and 15457885
Volume :
6
Issue :
8
Database :
Directory of Open Access Journals
Journal :
PLoS Biology
Publication Type :
Academic Journal
Accession number :
edsdoj.81f19f9f57a6460ca9d344ed62b73e38
Document Type :
article
Full Text :
https://doi.org/10.1371/journal.pbio.0060191