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

Details

Serval ID
serval:BIB_9E7371C18140
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Clonal deletion and the fate of autoreactive thymocytes that survive negative selection.
Journal
Nature Immunology
Author(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
Publication state
Published
Issued date
2012
Volume
13
Number
6
Pages
569-578
Language
english
Abstract
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.
Keywords
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
Create date
09/06/2012 17:50
Last modification date
20/08/2019 15:04
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