CCR7-mediated migration of developing thymocytes to the medulla is essential for negative selection to tissue-restricted antigens

T Nitta, S Nitta, Y Lei, M Lipp… - Proceedings of the …, 2009 - National Acad Sciences
T Nitta, S Nitta, Y Lei, M Lipp, Y Takahama
Proceedings of the National Academy of Sciences, 2009National Acad Sciences
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 …
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.
National Acad Sciences