Homing of immature thymocytes to the subcapsular microenvironment within the thymus is not an absolute requirement for T cell development.

Abstract

T cell development is thought to occur in distinct microenvironments within the thymus. Namely, the subcapsular zone, the cortex and the medulla have been described to support expansion of the immature thymocyte pool, positive selection of useful specificities and elimination of potentially self-reactive specificities, respectively. Consistent with this model, thymocytes show a highly ordered migration pattern and move into these niches in the expected sequence. Here we show that the chemokine receptor CCR9 plays a nonredundant role in the homing of immature thymocytes to the subcapsular zone. In CCR9-deficient mice, T cells in early stages of development do not accumulate in their physiological microenvironment underneath the thymic capsule and are instead homogeneously distributed across the thymic cortex. Remarkably, this abnormality does not result in a detectable defect in T cell development in CCR9-deficient mice, suggesting that the transit of immature thymocytes through the subcapsular microenvironment is not an absolute requirement for proper T cell development.