IL-2R alpha on one cell can present IL-2 to IL-2R beta/gamma(c) on another cell to augment IL-2 signaling

Abstract

IL-2Ralpha augments IL-2 signaling. Although this is generally believed to occur only when the three known components of IL-2R are associated within a single cell membrane, we demonstrate here an intercellular interaction. Cocultivation of cells individually expressing chimerae incorporating the extracellular domain of IL-2Ralpha alone with cells expressing chimerae of IL-2Rbeta alone permitted IL-2 dose-dependent oligomerization of the chimerae. Likewise, native IL-2Ralpha-bearing cells augmented the IL-2 proliferative response of ex vivo large granular lymphocytic leukemia cells expressing IL-2Rbeta/gamma(c) but lacking IL-2Ralpha. In both cases, the response was inhibitable by an Ab to IL-2Ralpha. Intercellular augmentation of cytokine effects, acting in trans, has important implications for biology and medicine.