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Soluble human interleukin-4 receptor is produced by activated T cells under the control of metalloproteinases

T Jung1, N Schrader, M Hellwig

  • 1Department of Dermatology, University of Göttingen, Germany. Thomas.Jung@Pharma.Novartis.Com

International Archives of Allergy and Immunology
|May 26, 1999
PubMed
Abstract

Insights

Human T cells actively produce soluble interleukin 4 receptors (sIL-4R) during immune responses, regulated by T cell receptor stimuli and cytokines. This inducible sIL-4R molecule antagonizes IL-4 activity, playing a key role in immune regulation.

Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • Soluble interleukin 4 receptors (sIL-4R) are found in biological fluids.
  • Human sIL-4R is thought to be produced by proteolytic cleavage of the cell surface receptor, unlike in mice.
  • The active production of human sIL-4R during immune responses remains unclear.

Purpose of the Study:

  • To investigate the production and regulation of soluble interleukin 4 receptors (sIL-4R) by human T cells.
  • To determine if sIL-4R is actively produced during immune responses.
  • To understand the role of sIL-4R as an immunoregulatory molecule.

Main Methods:

  • Human T cell subpopulations (CD4+, CD8+, CD45RA+, CD45R0+) were activated in vitro.
  • Soluble IL-4R (sIL-4R) levels in supernatants were measured.
  • Cell surface IL-4R expression was analyzed using flow cytometry and RT-PCR.

Main Results:

  • Recombinant sIL-4R inhibited IL-4-mediated T cell proliferation and IL-5 upregulation.
  • Activated T cells, including naive and memory subsets, produced high levels of sIL-4R with sustained kinetics.
  • T cell receptor engagement, IL-4, and interferon-gamma significantly enhanced sIL-4R production, while metalloproteinase inhibitors reduced shedding.

Conclusions:

  • Human T cells actively produce inducible soluble interleukin 4 receptors (sIL-4R) in response to T cell receptor stimuli, IL-4, and IFN-gamma.
  • Metalloproteinase activity is essential for the shedding of IL-4R.
  • Due to its IL-4-antagonizing properties, sIL-4R functions as a significant immunoregulatory molecule.

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