OX40–Mediated Cosignal Enhances the Maturation of Naive Human CD4+ T Cells into High IL–4–Producing Effectors

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Abstract
Our previous studies have indicated that naive human CD4+ T cells of neonatal or adult origin may be the initial source of IL–4 which is required for their development into Th2 effectors. In addition to minute amounts of IL–4, anti–CD3/B7.1–activated naive cells also release readily detectable levels of IL–13 and IFN–γ. The production of IL–4 and IL–13 by naive T cells is differentially regulated by TGF–β and IL–12. Shortly after activation, naive T cells express surface OX40, a TNF–R family member whose ligand (OX40L) is constitutively expressed on a subset of dendritic cells. Engagement of OX40 on activated naive T cells increases their expression of IL–4 and IL–13, suppresses that of IFN–γ and promotes their development into Th2–like effectors.