Clonal deletion and the fate of autoreactive thymocytes that survive negative selection.

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Etat: Public
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ID Serval
serval:BIB_9E7371C18140
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Clonal deletion and the fate of autoreactive thymocytes that survive negative selection.
Périodique
Nature Immunology
Auteur⸱e⸱s
Pobezinsky L.A., Angelov G.S., Tai X., Jeurling S., Van Laethem F., Feigenbaum L., Park J.H., Singer A.
ISSN
1529-2916 (Electronic)
ISSN-L
1529-2908
Statut éditorial
Publié
Date de publication
2012
Volume
13
Numéro
6
Pages
569-578
Langue
anglais
Résumé
Clonal deletion of autoreactive thymocytes is important for self-tolerance, but the intrathymic signals that induce clonal deletion have not been clearly identified. We now report that clonal deletion during negative selection required CD28-mediated costimulation of autoreactive thymocytes at the CD4(+)CD8(lo) intermediate stage of differentiation. Autoreactive thymocytes were prevented from undergoing clonal deletion by either a lack of CD28 costimulation or transgenic overexpression of the antiapoptotic factors Bcl-2 or Mcl-1, with surviving thymocytes differentiating into anergic CD4(-)CD8(-) double-negative thymocytes positive for the T cell antigen receptor αβ subtype (TCRαβ) that 'preferentially' migrated to the intestine, where they re-expressed CD8α and were sequestered as CD8αα(+) intraepithelial lymphocytes (IELs). Our study identifies costimulation by CD28 as the intrathymic signal required for clonal deletion and identifies CD8αα(+) IELs as the developmental fate of autoreactive thymocytes that survive negative selection.
Mots-clé
Animals, Antigens, CD28/immunology, Antigens, CD4/immunology, Antigens, CD8/immunology, Cell Differentiation/immunology, Clonal Deletion/immunology, Flow Cytometry, Immune Tolerance/immunology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Receptors, Antigen, T-Cell/immunology, Signal Transduction/immunology, Thymocytes/cytology, Thymocytes/immunology, Thymus Gland/cytology, Thymus Gland/immunology
Pubmed
Web of science
Création de la notice
09/06/2012 17:50
Dernière modification de la notice
30/04/2021 6:13
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