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Publication : Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus.

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.
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