Proposed model of Foxp3 induction by malaria-infected RBCs.

<p>Upon exposure to malaria-infected RBCs, monocytes interact with CD4⁺ T cells via MHC class II (1), which induces IL-2 and IL-10 secretion from these cells (2). IL-2 contributes to the conversion of CD4⁺CD25⁻ into CD25^hiFoxp3^int cells (3). Additionally, CD4⁺ T cell-derived IL-2 in conjunction with monocyte and T cell-derived IL-10 and TGFβ acts on bystander CD4⁺CD25⁻ T cells as well as CD4⁺CD25⁺ nTregs, that have not interacted with monocytes and therefore received no signal through their TCR themselves (4). This drives/enhances Foxp3 expression in these cells, resulting in the generation of CD25^hiFoxp3^hi CD4 T cells (5). These CD25^hiFoxp3^hi CD4 T cells in turn regulate the production of the Th effector cytokines IFNγ, IL-4 and IL-17 by parasite-induced CD25^hiFoxp3^int CD4 T cells (6).