Thymic T cell export is not influenced by the peripheral T cell pool.

The peripheral T cell pool is maintained both by export of naive T cells from the thymus and by post-thymic expansion of activated/memory T cells. However, it is not known whether the thymus can alter its output following peripheral T cell depletion. Using intrathymic injection of fluorescein isothiocyanate to detect recent thymic emigrants (RTE), we directly tested whether the thymus is able to alter the number of RTE or the CD4:CD8 ratio of RTE emigrating to the periphery in response to in vivo depletion of total peripheral T cells or CD4 T cells, respectively. Depletion of peripheral T cells was achieved with anti-Thy-1 or anti-CD4, at doses that did not affect thymocyte numbers. Depletion of greater than 70% of peripheral T cells by treatment with anti-Thy-1 in vivo did not alter the number or cell cycle status of RTE trafficking to lymph nodes or spleen during the peripheral reconstitution phase (6, 9, 12 days). Similarly, depletion of the majority of CD4 T cells, which significantly reduced the peripheral CD4:CD8 T cell ratio, did not alter the total number or the proportion of CD4+ CD8- RTE in peripheral lymphoid organs. These data clearly indicate that thymic output is not influenced by downstream alterations in peripheral T cell pool size or CD4:CD8 ratio. Rather we contend that thymic T cell export is internally regulated by as yet undefined mechanisms.