Infectious Tolerance: Human CD25(+) Regulatory T Cells Convey Suppressor Activity to Conventional CD4(+) T Helper Cells

Regulatory CD4(+)CD25(+) T cells (Treg) are mandatory for maintaining immunologic self-tolerance. We demonstrate that the cell-cell contact–mediated suppression of conventional CD4(+) T cells by human CD25(+) Treg cells is fixation resistant, independent from membrane-bound TGF-β but requires activation and protein synthesis of CD25(+) Treg cells. Coactivation of CD25(+) Treg cells with Treg cell–depleted CD4(+) T cells results in anergized CD4(+) T cells that in turn inhibit the activation of conventional, freshly isolated CD4(+) T helper (Th) cells. This infectious suppressive activity, transferred from CD25(+) Treg cells via cell contact, is cell contact–independent and partially mediated by soluble transforming growth factor (TGF)-β. The induction of suppressive properties in conventional CD4(+) Th cells represents a mechanism underlying the phenomenon of infectious tolerance. This explains previously published conflicting data on the role of TGF-β in CD25(+) Treg cell–induced immunosuppression.