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

J Immunol. 1998 Nov 15;161(10):5430-7.

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.

MeSH terms

  • Adjuvants, Immunologic / physiology*
  • Antigen Presentation* / genetics
  • Antigens, Polyomavirus Transforming / genetics
  • Cell Communication / genetics
  • Cell Communication / immunology
  • Cell Line
  • Coculture Techniques
  • Humans
  • Interleukin-2 / immunology*
  • Interleukin-2 / metabolism*
  • Intracellular Fluid / metabolism
  • Jurkat Cells
  • Leukemia, Lymphoid / metabolism
  • Lymphocyte Activation
  • Membrane Proteins / genetics
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Interleukin-2 / genetics
  • Receptors, Interleukin-2 / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / genetics
  • Signal Transduction / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes / radiation effects
  • Transfection / immunology
  • Tumor Cells, Cultured

Substances

  • Adjuvants, Immunologic
  • Antigens, Polyomavirus Transforming
  • Interleukin-2
  • Membrane Proteins
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • antigen T cell receptor, zeta chain