ICOS:B7RP-1 and other major costimulatory receptor–ligand pairs. ICOS is expressed mainly on activated T cells and resting memory cells while its ligand, B7RP-1, is constitutively expressed on APCs and also on fibroblasts and endothelial and epithelial cells. Like the CD28:B7-1/2 pathway, the ICOS-ICOSL pathway can enhance T-cell proliferation, CD154 expression, and cytokine production. Both in vitro and in vivo studies indicate that ICOS-ICOSL costimulation contributes to the production of the effector cytokines interferon γ (IFNγ), tumor necrosis factor α (TNFα), granulocyte-macrophage colony-stimulating factor (GMCSF), interleukin 4 (IL-4), IL-5, IL-13, and IL-10 but little IL-2. It is thought that ICOS-ICOSL costimulation may have a more critical role regulating T-helper 2 (TH₂)–cell differentiation than it does regulating T-cell expansion.^3 -5