Article abstract
Nature Immunology 10, 823 - 830 (2009)
Published online: 21 June 2009 | doi:10.1038/ni.1761
The impact of negative selection on thymocyte migration in the medulla
Marie Le Borgne1,3,4, Ena Ladi1,4, Ivan Dzhagalov1, Paul Herzmark1, Ying Fang Liao1, Arup K Chakraborty2 & Ellen A Robey1
Abstract
Developing thymocytes are screened for self-reactivity before they exit the thymus, but how thymocytes scan the medulla for self antigens is unclear. Using two-photon microscopy, we observed that medullary thymocytes migrated rapidly and made frequent, transient contacts with dendritic cells. In the presence of a negative selecting ligand, thymocytes slowed, became confined to areas of approximately 30 
m in diameter and had increased contact with dendritic cells surrounding confinement zones. One third of polyclonal medullary thymocytes also showed confined, slower migration and may correspond to autoreactive thymocytes. Our data suggest that many autoreactive thymocytes do not undergo immediate arrest and death after encountering a negative selecting ligand but instead adopt an altered migration program while remaining in the medullary microenvironment.
- Division of Immunology, Department of Molecular and Cell Biology, University of California, Berkeley, California, USA.
- Department of Chemistry, Department of Chemical Engineering and Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
- Present address: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
- These authors contributed equally to this work.
Correspondence to: Ellen A Robey1 e-mail: erobey@berkeley.edu
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