| First Author | Pobezinsky LA | Year | 2012 |
| Journal | Nat Immunol | Volume | 13 |
| Issue | 6 | Pages | 569-78 |
| PubMed ID | 22544394 | Mgi Jnum | J:186451 |
| Mgi Id | MGI:5432326 | Doi | 10.1038/ni.2292 |
| Citation | Pobezinsky LA, et al. (2012) Clonal deletion and the fate of autoreactive thymocytes that survive negative selection. Nat Immunol 13(6):569-78 |
| abstractText | 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 alphabeta subtype (TCRalphabeta) that 'preferentially' migrated to the intestine, where they re-expressed CD8alpha and were sequestered as CD8alphaalpha(+) intraepithelial lymphocytes (IELs). Our study identifies costimulation by CD28 as the intrathymic signal required for clonal deletion and identifies CD8alphaalpha(+) IELs as the developmental fate of autoreactive thymocytes that survive negative selection. |
