Clonal deletion and the fate of autoreactive thymocytes that survive negative selection.
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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
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
30/04/2021 6:13