The impact of negative selection on thymocyte migration in the medulla

• Published in: Nature immunology Vol. 10; no. 8; pp. 823 - 830
• Main Authors: Le Borgne, Marie, Ladi, Ena, Dzhagalov, Ivan, Herzmark, Paul, Liao, Ying Fang, Chakraborty, Arup K, Robey, Ellen A
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.08.2009; Nature Publishing Group
• Subjects: Animals; Autoimmunity; Biomedical and Life Sciences; Biomedicine; Cell Differentiation; Cell Movement; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - physiology; Forkhead Transcription Factors - metabolism; Immunology; Infectious Diseases; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microscopy; Physiological aspects; Properties; Receptors, Antigen, T-Cell - immunology; T cells; T-Lymphocytes - cytology; T-Lymphocytes - immunology; T-Lymphocytes - physiology; Thymus Gland - cytology; Thymus Gland - immunology; United States
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.1761

Self-reactive thymocytes are eliminated through negative selection in the thymic medulla. Robey and colleagues find that autoreactive thymocytes show slower and more confined migration than that of polyclonal thymocytes 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 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.