LPS-activated monocytes suppress T-cell immune responses and induce FOXP3+T cells through a COX-2-PGE2-dependent mechanism

Monocytes initiate innate immune responses and interact with T cells to induce antigen-specific immune responses by antigen presentation and secretion of humoral factors. We have previously shown that adaptive regulatory T cells inhibit T-cell effector functions in a cyclooxygenase (COX)-2-prostaglandin E-2 (PGE(2))-dependent manner and that PGE(2) converts resting CD4+CD25- T cells into FOXP3+ T cells with a suppressive phenotype. Here, we demonstrate that stimulation of monocytes with LPS leads to suppression of T-cell immune responses by a COX-2-PGE(2)-dependent mechanism that is reversible with COX-2 inhibitors as well as PGE(2)-neutralizing antibody and cAMP antagonist. Furthermore, we show that LPS-activated monocytes induce FOXP3 expression in resting CD4+CD25- T cells by the same pathway. These results suggest that monocytes are able to efficiently suppress T-cell immune responses in a regulatory manner and elicit an inhibitory immune profile.