The Role of the Thymus and Recent Thymic Migrants in the Maintenance of the Adult Peripheral Lymphocyte Pool

TLDR

The thymus is essential for the initial seeding of T cells to the periphery, but its role in maintaining the adult T cell pool remains poorly defined. We investigated whether changes to the rate of T cell export could form part of the mechanism(s) controlling the homeostatic regulation of the size and composition of the peripheral T cell pool. We examined how variations in thymic export rate influence peripheral T cell homeostasis and tracked recent thymic emigrants to assess their acceptance into the normal mouse T cell pool. Using neonatal thymic grafts and thymectomy, we found that thymic export rate is constant regardless of supply level, keeping the peripheral T cell pool size stable; recent thymic emigrants are phenotypically mature but initially have a CD4/CD8 ratio twice that of resident cells, which falls after entry, indicating separate thymic and peripheral regulation; RTE preferentially enter the periphery, displacing resident cells and maintaining pool size, and their acceptance preserves repertoire diversity.

Abstract

The thymus is essential for the initial seeding of T cells to the periphery, but its role in maintaining the adult T cell pool remains poorly defined. We investigated whether changes to the rate of T cell export could form part of the mechanism(s) controlling the homeostatic regulation of the size and composition of the peripheral T cell pool. Using neonatal thymi grafted under the kidney capsule, we found that irrespective of whether the pool was oversupplied (by thymic grafts) or undersupplied (due to neonatal thymectomy), the thymic export rate was constant from both the host and graft thymus, and the periphery remained constant in size. Recent thymic emigrants (RTE) were also tracked to determine the extent of their acceptance into the T cell pool of a normal mouse. As a population, RTE are phenotypically mature, but were distinct from resident T cells in the periphery, being released in a CD4/CD8 ratio approximately twice that of established peripheral T cells. This export ratio is similar to that of T cells in the mature thymic compartment, but soon after entry into the periphery, the ratio falls, indicating separate thymic and peripheral regulation of the CD4/CD8 ratio. RTE may also be preferentially incorporated into the periphery, causing displacement of resident T cells, thus maintaining the size of the peripheral pool. Although not vital for the maintenance of a functional T cell pool, the acceptance of RTE in a "full" peripheral pool would ensure that the T cell receptor repertoire is kept diverse and that the T cell population encompasses a broad range of naive as well as memory T cells.