The impact of negative selection on thymocyte migration in the medulla

Marie Le Borgne, Ena Ladi, Ivan Dzhagalov, Paul Herzmark, Ying Fang Liao, Arup K. Chakraborty, Ellen A. Robey*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

115 Scopus citations

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 μm 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.

Original languageEnglish
Pages (from-to)823-830
Number of pages8
JournalNature Immunology
Volume10
Issue number8
DOIs
StatePublished - 2009

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