The impact of negative selection on thymocyte migration in the medulla.
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 microm 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.
Le Borgne
Marie
M
Department of Molecular and Cell Biology, University of California, Berkeley, USA.
Ladi
Ena
E
Dzhagalov
Ivan
I
Herzmark
Paul
P
Liao
Ying Fang
YF
Chakraborty
Arup K
AK
Robey
Ellen A
EA
D000818:Animals; D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D011948:Receptors, Antigen, T-Cell