IL-2R alpha on one cell can present IL-2 to IL-2R beta/gamma(c) on another cell to augment IL-2 signaling.
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.
Eicher
D M
DM
Metabolism Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Waldmann
T A
TA
D000276:Adjuvants, Immunologic / Q000502:physiology*; D017951:Antigen Presentation / Q000235:genetics; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics; D002450:Cell Communication / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D018920:Coculture Techniques; D006801:Humans; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism*; D007424:Intracellular Fluid / Q000378:metabolism; D019169:Jurkat Cells; D007945:Leukemia, Lymphoid / Q000378:metabolism; D008213:Lymphocyte Activation; D008565:Membrane Proteins / Q000235:genetics; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000378:metabolism / Q000528:radiation effects; D014162:Transfection / Q000276:immunology; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000952:Antigens, Polyomavirus Transforming; D007376:Interleukin-2; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; C054979:antigen T cell receptor, zeta chain