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Nat Immunol. 2006 Oct;7(10):1092-100. Epub 2006 Sep 3.

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

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The CBR Institute for Biomedical Research, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, 02115, USA.

Erratum in

  • Nat Immunol. 2006 Nov;7(11):1234.


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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