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- Title
Clonal deletion and the fate of autoreactive thymocytes that survive negative selection.
- Authors
Pobezinsky, Leonid A; Angelov, Georgi S; Tai, Xuguang; Jeurling, Susanna; Van Laethem, François; Feigenbaum, Lionel; Park, Jung-Hyun; Singer, Alfred
- 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.
- Publication
Nature immunology, 2012, Vol 13, Issue 6, p569
- ISSN
1529-2916
- Publication type
Journal Article
- DOI
10.1038/ni.2292