First Author | Bonasio R | Year | 2006 |
Journal | Nat Immunol | Volume | 7 |
Issue | 10 | Pages | 1092-100 |
PubMed ID | 16951687 | Mgi Jnum | J:112629 |
Mgi Id | MGI:3662948 | Doi | 10.1038/ni1385 |
Citation | Bonasio R, et al. (2006) Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus. Nat Immunol 7(10):1092-100 |
abstractText | Dendritic cell (DC) presentation of self antigen to thymocytes is essential to the establishment of central tolerance. We show here that circulating DCs were recruited to the thymic medulla through a three-step adhesion cascade involving P-selectin, interactions of the integrin VLA-4 with its ligand VCAM-1, and pertussis toxin-sensitive chemoattractant signaling. Ovalbumin-specific OT-II thymocytes were selectively deleted after intravenous injection of antigen-loaded exogenous DCs. We documented migration of endogenous DCs to the thymus in parabiotic mice and after painting mouse skin with fluorescein isothiocyanate. Antibody to VLA-4 blocked the accumulation of peripheral tissue-derived DCs in the thymus and also inhibited the deletion of OT-II thymocytes in mice expressing membrane-bound ovalbumin in cardiac myocytes. These findings identify a migratory route by which peripheral DCs may contribute to central tolerance. |