Numerous disease states, such as human allergic, autoimmune, and autoimmune diseases, and cancer, may be treated by targeting OX40/OX4OL. OX4OL inhibits the generation of Tr1 cells from naïve and memory CD4+ T cells. This unique function of OX4OL is not shared by two other costimulatory TNF-family members, GITR-ligand and 4-1BB-ligand. It has been shown that signaling the OX40-receptor on human T cells by antibodies, small molecules, or the OX4OL modulates the generation and function of IL-10 producing Foxp3+ Treg immunosuppressive T cells and blocks Foxp3+ Treg function. Further, provided are high throughput methods for identifying compounds that can inhibit the immunosuppressive function of IL-10 producing Tr1 cells.