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Nociceptin/orphanin FQ modulates human T cell function in vitro

Paula S Waits1, Wendy M Purcell, Allison J Fulford

  • 1Faculty of Applied Sciences, Centre for Research in Biomedicine, University of the West of England, Coldharbour Lane, Frenchay, Bristol, BS16 1QY, UK.

Journal of Neuroimmunology
|March 17, 2004
PubMed

Insights

Nociceptin/orphanin FQ (N/OFQ) influences human T cell activation, enhancing proliferation and modulating TNF-alpha secretion. It also inhibits re-stimulated T cells by up-regulating CTLA-4, partly via prostaglandin synthesis.

Area of Science:

  • Immunology
  • Neuroendocrinology
  • Cellular Biology

Background:

  • The nociceptin/orphanin FQ (N/OFQ) peptide and its receptor (ORL-1) are widely expressed in immune cells.
  • The precise function of the N/OFQ system in immune responses, particularly T cell activation, remains largely undefined.

Purpose of the Study:

  • To investigate the role of N/OFQ in modulating human T cell activation and function.
  • To elucidate the mechanisms underlying N/OFQ's effects on T cells, including potential involvement of prostaglandins.

Main Methods:

  • Human T cells were treated with varying concentrations of N/OFQ.
  • T cell activation markers (e.g., CD28), proliferation, and TNF-alpha secretion were assessed.
  • CTLA-4 expression and prostaglandin synthesis were analyzed in response to N/OFQ stimulation.

Main Results:

  • N/OFQ (10(-14)-10(-12) M) upregulated activation markers like CD28, enhancing T cell proliferation and modulating TNF-alpha secretion.
  • On re-stimulated T cells, N/OFQ inhibited proliferation, correlating with increased CTLA-4 expression.
  • N/OFQ was found to induce prostaglandin synthesis, and some of its effects were partly prostaglandin-dependent.

Conclusions:

  • N/OFQ plays a significant modulatory role in human T cell activation and function.
  • The peptide influences T cell responses through mechanisms involving both activation and inhibition, potentially mediated by prostaglandin synthesis.

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