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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 (TCM) and effector‐memory T cells (TEM) pools after adoptive transfer of sorted CD8+ T cells from naïve, TCM and TEM 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 naïve 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 TCM and TEM fractions, and leading to repopulation of each pool with progeny of its own kind.