Journal
NATURE IMMUNOLOGY
Volume 10, Issue 8, Pages 823-U41Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1761
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Funding
- NIAID NIH HHS [R01 AI064227, R01 AI053039-02, R01 AI064227-04, R01 AI064227-01A2, R01 AI064227-03, R01 AI064227-02, R01 AI053039, R01 AI053039-01, R01 AI053039-04, R01 AI053039-03] Funding Source: Medline
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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 mu 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.
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