Differential control of immune cell homeostasis by Foxp3 ⁺ regulatory T cells in murine peripheral lymph nodes and spleen

Abstract

Foxp3 ⁺ regulatory T cells (Tregs) hamper efficient immune responses to tumors and chronic infections. Therefore, depletion of Foxp3 ⁺ Tregs has been proposed as therapeutic option to boost immune responses and to improve vaccinations. Although Treg-mediated control of T cell homeostasis is well established, Foxp3 ⁺ Treg interaction with other immune cell subsets is only incompletely understood. Thus, the present study aimed at examining dynamic effects of experimental Foxp3 ⁺ Treg depletion on a broad range of immune cell subsets, including B cells, natural killer cells, and myeloid cells. Striking differences were observed when peripheral lymph nodes (LN) and spleen were compared. B cells, for example, showed a massive and long-lasting accumulation only in LN but not in spleen of transiently Treg-depleted mice. In contrast, monocyte-derived dendritic cells, which are potent inducers of T cell responses, also accumulated selectively, but only transiently in LN, suggesting that this cell population is under very strict control of Foxp3 ⁺ Tregs. In summary, the observations described here provide insights into the dynamics of immune cells after selective depletion of Foxp3 ⁺ Tregs. This will allow a better prediction of the impact of Treg ablation in translational studies that aim at boosting immune responses and vaccinations.