CCR7-mediated migration of developing thymocytes to the medulla is essential for negative selection to tissue-restricted antigens.
Immature double-positive thymocytes are generated in the thymic cortex, and on positive selection, are induced to differentiate into mature single-positive thymocytes and relocate to the medulla. CCR7 is pivotal for cortex-to-medulla migration of positively selected thymocytes, and CCR7-mediated migration to the medulla is essential for establishing central tolerance, thereby, preventing tissue-specific autoimmunity. However, it was unclear how CCR7-mediated migration to the medulla affects the establishment of self-tolerance. Here, we show that the deletion of thymocytes specific for insulin-promoter-driven tissue-restricted antigens (TRAs) is significantly impaired in CCR7- or CCR7-ligand-deficient mice. These results indicate that CCR7-mediated migration to the medulla contributes to the negative selection of TRA-reactive thymocytes.
Nitta
Takeshi
T
Division of Experimental Immunology, Institute for Genome Research, University of Tokushima, Tokushima 770-8503, Japan.
Nitta
Sachiko
S
Lei
Yu
Y
Lipp
Martin
M
Takahama
Yousuke
Y
D000818:Animals; D000941:Antigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D007108:Immune Tolerance / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D054400:Receptors, CCR7 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000941:Antigens; C515371:Ccr7 protein, mouse; D011948:Receptors, Antigen, T-Cell; D054400:Receptors, CCR7