Developmental regulation of Foxp3 expression during ontogeny

JD Fontenot, JL Dooley, AG Farr… - The Journal of …, 2005 - rupress.org
JD Fontenot, JL Dooley, AG Farr, AY Rudensky
The Journal of experimental medicine, 2005rupress.org
Thymectomy of neonatal mice can result in the development of autoimmune pathology. It
has been proposed that thymic output of regulatory T (T reg) cells is delayed during
ontogeny and that the development of autoimmune disease in neonatally thymectomized
mice is caused by the escape of self-reactive T cells before thymectomy without
accompanying T reg cells. However, the kinetics of T reg cell production within the thymus
during ontogeny has not been assessed. We demonstrate that the development of Foxp3 …
Thymectomy of neonatal mice can result in the development of autoimmune pathology. It has been proposed that thymic output of regulatory T (T reg) cells is delayed during ontogeny and that the development of autoimmune disease in neonatally thymectomized mice is caused by the escape of self-reactive T cells before thymectomy without accompanying T reg cells. However, the kinetics of T reg cell production within the thymus during ontogeny has not been assessed. We demonstrate that the development of Foxp3-expressing T reg cells is substantially delayed relative to nonregulatory thymocytes during ontogeny. Based on our data, we speculate that induction of Foxp3 in developing thymocytes and, thus, commitment to the T reg cell lineage is facilitated by a signal largely associated with the thymic medulla.
rupress.org