Role of LFA-1/ICAM-1 in interleukin-2-stimulated lymphocyte proliferation

F A Vyth-Dreese, T A Dellemijn, A Frijhoff, Y van Kooyk, C G Figdor

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Major adhesion routes between lymphoid cells involve the receptor/ligand pairs LFA-1/ICAM-1 and CD2/LFA-3, in addition to VLA or CD44 molecules. In this study we evaluated the role of these adhesion receptors in the proliferative response of lymphoid cells to interleukin-2 (IL-2). Blocking studies were performed with a panel of monoclonal antibodies (mAb) directed against these adhesion molecules. Selective inhibition of recombinant (r)IL-2-induced cell proliferation was observed with mAb directed against the alpha or beta subunit of LFA-1 or to its ligand ICAM-1. Interestingly, rIL-2-induced proliferation was also inhibited by NKI-L16, and anti-1 alpha antibody known to enhance cell-cell interaction. Resting lymphocytes were preferentially susceptible to the inhibition, particularly in an early phase of culture and when stimulated with a relatively low dose of rIL-2. By using mAb that specifically could block distinct rIL-2 activation pathways, LFA-1/ICAM-1 interaction was found to be required for p55 IL-2 receptor (IL-2R)-mediated interaction of rIL-2 with its high-affinity receptor, but not for p75 IL-2R-mediated responses. Furthermore, it was shown that the rIL-2 response of T lymphocytes, but not of natural killer cells, was dependent on LFA-1/ICAM-1 interaction. This suggests that LFA-1/ICAM-1 interaction is required for an optimal rIL-2 response of cells capable of IL-2 secretion. Our data provide evidence for the hypothesis that adhesion receptor-directed release of IL-2 may result in a locally high concentration of IL-2 that triggers high-affinity IL-2R signaling and up-regulates p55 IL-2R to enhance cytokine responsiveness.

Original languageEnglish
Pages (from-to)3292-9
Number of pages8
JournalEuropean journal of immunology
Issue number12
Publication statusPublished - Dec 1993


  • Antibodies, Monoclonal/immunology
  • Cell Adhesion Molecules/physiology
  • Cells, Cultured
  • Humans
  • Intercellular Adhesion Molecule-1
  • Interleukin-2/pharmacology
  • Killer Cells, Natural/drug effects
  • Lymphocyte Activation/drug effects
  • Lymphocyte Function-Associated Antigen-1/physiology
  • Receptors, Interleukin-2/physiology
  • Recombinant Proteins/pharmacology
  • T-Lymphocytes/drug effects

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