Fig. 2. Regulatory T-cell cascade following induction of Th3 type Tregs by oral antigen or oral anti-CD3.

A Th3 cell is a CD4⁺CD25⁻Foxp3⁻LAP⁺ cell that exists in the peripheral immune compartment and is triggered by TCR signaling in the gut by oral antigen. Following triggering in the gut, the Th3 cell secretes TGF-β. Secreted TGF-β acts to maintain naturally occurring CD4⁺CD25⁺Foxp3⁺ Tregs, suppress Th1 and Th2 responses, and in concert with IL-6 may induce Th17 responses. Secreted TGF-β from Th3 cells also acts on CD4⁺Foxp3⁻ cells and converts them to iTregs, which are Foxp3⁺CD25⁺LAP⁻. Depending on the milieu, these cells may become Foxp3⁺CD4⁺CD25⁺LAP⁺. These induced Tregs may also condition DCs to secrete IL-27 and in turn induce IL-10-secreting Tr1 cells.