The impact of negative selection on thymocyte migration in the medulla

Developing thymocytes are screened for self-reactivity before exiting 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 microns in diameter, and had increased contact with dendritic cells surrounding confinement zones. One third of polyclonal medullary thymocytes also exhibited confined, slower migration, and may correspond to auto-reactive thymocytes. Our data suggest that many auto-reactive thymocytes do not undergo immediate arrest and death upon encounter with a negative selecting ligand, but rather adopt an altered migration program while remaining within the medullary microenvironment.