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

Abstract

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.

Maturation of Lymphocyte Immunophenotypes and Memory T Helper Cell Differentiation During Development in Mice

“…Thus, profiles of the two studies are congruent. These data, measured as proportions of total lymphocytes and absolute numbers, indicate and support other reports (Gabor et al, 1997;Modigliani et al, 1994), that thymic exportation of T cells exponentially increases between d3 and dl0. The increase in spleen cellularity during the neonatal period, therefore, is primarily due to thymic exportation rather than in situ proliferation (Modigliani et al, 1994).…”

Linkage analysis of variations in CD4:CD8 T cell subsets between C57BL/6 and DBA/2

“…These results indicated that the ratios of CD4 to CD8 in the organ in which most ␣␤TCR + T cells are generated, the thymus, do not necessarily predict ratios in the periphery, an observation that has been reported before. 17 Consequently the CD4:CD8 values in the thymus and periphery are almost certainly controlled by different genes, at least in the strain combination studied here.…”

“…For example, depletion of peripheral CD4 + T cells does not lead to increased production of CD4 + cells by the thymus. 17 Therefore it is likely that genes other than those thought to affect T cell maturation; for example, genes that act exclusively on mature T cells; may also affect the ratio of CD4:CD8 T cells in the periphery.…”

Phosphatidylinositol 3-Kinase Regulates the CD4/CD8 T Cell Differentiation Ratio

“…2E; p ϭ 0.007), indicating that CD4 ϩ thymocytes exit the thymus more efficiently in Tg mice. As an alternative approach, FITC was injected into the thymus of Wt and p65 PI3K Tg mice; 48 h postinjection, we examined the appearance of FITClabeled recent thymic emigrants in the periphery (29,30,33). The number of FITC-labeled CD4 ϩ thymic emigrants was consistently higher in p65 PI3K Tg than in Wt littermates ( Fig.…”

“…Briefly, BrdU was administrated for 8 days in drinking water to wild type (Wt) and p65 PI3K Tg mice, and then the presence of spleen T cells incorporating BrdU low was examined by flow cytometry. Intrathymic FITC injections and analysis of recent thymic emigrants were as described (29,30). Cells were analyzed on an EPICS XL using System II software (Coulter, Miami, FL).…”