Nature Immunology
- 7, 1092 - 1100 (2006)
Published online: 3 September 2006; Corrected online: 29 September 2006 | doi:10.1038/ni1385
There is a Corrigendum (November 2006) associated with this Article.
Clonal deletion of thymocytes by circulating dendritic cells homing to the thymusRoberto Bonasio1, M Lucila Scimone1, Patrick Schaerli1, Nir Grabie2, Andrew H Lichtman2 & Ulrich H von Andrian11
The CBR Institute for Biomedical Research, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA. 2
Immunology Research Division and Vascular Research Division, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA.
Correspondence should be addressed to Ulrich H von Andrian uva@cbr.med.harvard.edu 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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