Figure 2.

Activation of anti-Tregs boosts immunity in vitro. Anti-Tregs are able to boost specific immunity against virus or tumor antigens in human peripheral blood mononuclear cells (PBMC). When stimulating PBMC with a known HLA-restricted, viral T cell epitope and interleukin-2 (IL-2), virus-specific T cells (green) begin to expand. The activation of anti-Tregs by the costimulation with an anti-Treg epitope (bottom), eg, programmed death-ligand 1 (PD-L1) or indoleamine 2,3-dioxygenase (IDO) peptides, facilitates further expansion of virus-specific T cells and a decrease in the numbers of Tregs (red), compared with cultures costimulated with an irrelevant control peptide, eg, an HIV peptide epitope (top). This “supportive” effect of anti-Tregs on immune effector cells may well be mediated in several direct and indirect manners, which may depend on the anti-Treg antigen. Of note, IDO⁺ cells may well be immune suppressive by other means than by the expression of IDO. Hence, the IDO⁺ cells may in addition express, eg, Arginase, PD-L1, and immune regulatory cytokines (eg, interleukin-10 and transforming growth factor (TGF)–β). IDO-specific anti-Tregs may therefore not only reduce IDO-mediated suppression directly but in addition further immune suppression mediated by IDO⁺ regulatory cells.