CD4+CD25+ Treg regulate the contribution of CD8+ T-cell subsets in repopulation of the lymphopenic environment

Peripheral T-cell expansion is of major relevance for immune function after lymphopenia. In order to promote regeneration, the process should result in a peripheral T-cell pool with a similar subpopulation structure as before lymphopenia. We investigated the repopulation of the CD8(+) central-memory T cells (T-CM) and effector-memory T cells (T-EM) pools after adoptive transfer of sorted CD8(+) T cells from naive, T-CM and T-EM subsets into T-cell-deficient hosts. We show that the initial kinetics of expansion are distinct for each subset and that the contribution to the repopulation of the CD8(+) T-cell pool by the progeny of each subset is not a mere function of its initial expansion. We demonstrate that CD4(+)CD25(+) Treg play a major role in the repopulation of the CD8(+) T-cell pool and that CD8(+) T-cell subsets impact on each other. In the absence of CD4(+)CD25(+) Treg, a small fraction of naive CD8(+) T cells strongly proliferates, correlating with further expansion and differentiation of co-expanding CD8(+) T cells. CD4(+)CD25(+) Treg suppress these responses and lead to controlled repopulation, contributing decisively to the maintenance of recovered T-CM and T-EM fractions, and leading to repopulation of each pool with progeny of its own kind.