Clonal deletion and the fate of autoreactive thymocytes that survive negative selection View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2012-06

AUTHORS

Leonid A Pobezinsky, Georgi S Angelov, Xuguang Tai, Susanna Jeurling, François Van Laethem, Lionel Feigenbaum, Jung-Hyun Park, Alfred Singer

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. More... »

PAGES

569

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ni.2292

DOI

http://dx.doi.org/10.1038/ni.2292

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1032395563

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/22544394


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