Autoreactive T cells bypass negative selection and respond to self-antigen stimulation during infection.

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Serval ID
serval:BIB_AE177F209BFD
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Autoreactive T cells bypass negative selection and respond to self-antigen stimulation during infection.
Journal
Journal of Experimental Medicine
Author(s)
Enouz S., Carrié L., Merkler D., Bevan M.J., Zehn D.
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Publication state
Published
Issued date
2012
Volume
209
Number
10
Pages
1769-1779
Language
english
Notes
Publication types: Journal Article
Abstract
Central and peripheral tolerance prevent autoimmunity by deleting the most aggressive CD8(+) T cells but they spare cells that react weakly to tissue-restricted antigen (TRA). To reveal the functional characteristics of these spared cells, we generated a transgenic mouse expressing the TCR of a TRA-specific T cell that had escaped negative selection. Interestingly, the isolated TCR matches the affinity/avidity threshold for negatively selecting T cells, and when developing transgenic cells are exposed to their TRA in the thymus, only a fraction of them are eliminated but significant numbers enter the periphery. In contrast to high avidity cells, low avidity T cells persist in the antigen-positive periphery with no signs of anergy, unresponsiveness, or prior activation. Upon activation during an infection they cause autoimmunity and form memory cells. Unexpectedly, peptide ligands that are weaker in stimulating the transgenic T cells than the thymic threshold ligand also induce profound activation in the periphery. Thus, the peripheral T cell activation threshold during an infection is below that of negative selection for TRA. These results demonstrate the existence of a level of self-reactivity to TRA to which the thymus confers no protection and illustrate that organ damage can occur without genetic predisposition to autoimmunity.
Pubmed
Web of science
Open Access
Yes
Create date
01/11/2012 19:40
Last modification date
20/08/2019 16:17
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