| First Author | Cozzo Picca C | Year | 2011 |
| Journal | Proc Natl Acad Sci U S A | Volume | 108 |
| Issue | 36 | Pages | 14890-5 |
| PubMed ID | 21873239 | Mgi Jnum | J:176456 |
| Mgi Id | MGI:5291873 | Doi | 10.1073/pnas.1103810108 |
| Citation | Cozzo Picca C, et al. (2011) CD4+CD25+Foxp3+ regulatory T cell formation requires more specific recognition of a self-peptide than thymocyte deletion. Proc Natl Acad Sci U S A 108(36):14890-5 |
| abstractText | CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cells are generated during thymocyte development and play a crucial role in preventing the immune system from attacking the body's cells and tissues. However, how the formation of these cells is directed by T-cell receptor (TCR) recognition of self-peptide:major histocompatibility complex (MHC) ligands remains poorly understood. We show that an agonist self-peptide with which a TCR is strongly reactive can induce a combination of thymocyte deletion and CD4(+)CD25(+)Foxp3(+) Treg cell formation in vivo. A weakly cross-reactive partial agonist self-peptide could similarly induce thymocyte deletion, but failed to induce Treg cell formation. These studies indicate that CD4(+)CD25(+)Foxp3(+) Treg cell formation can require highly stringent recognition of an agonist self-peptide by developing thymocytes. They also refine the 'avidity' model of thymocyte selection by demonstrating that the quality of the signal mediated by agonist self-peptides, rather than the overall intensity of TCR signaling, can be a critical factor in directing autoreactive thymocytes to undergo CD4(+)CD25(+)Foxp3(+) Treg cell formation and/or deletion during their development. |
