Tumor-derived macrophage migration inhibitory factor (MIF) inhibits T lymphocyte activation

Xiaocai Yan, Rimas J. Orentas*, Bryon D. Johnson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Macrophage migration inhibitory factor (MIF) is a multi-functional cytokine that is considered a pro-inflammatory cytokine. However, our studies show that MIF, when produced in super-physiological levels by a murine neuroblastoma cell line (Neuro-2a) exceeding those normally seen during an immune response, inhibits cytokine-, CD3-, and allo-induced T-cell activation. MIF is also able to inhibit T cells that have already received an activation signal. The T-cell inhibitory effects of culture supernatants from neuroblastoma cells were reversed when the cells were transfected with dicer-generated si-RNA to MIF. When T cells were activated in vitro by co-culture with interleukin (IL)-2 and IL-15 and analyzed for cytokine production in the presence or absence of MIF-containing culture supernatant, inhibition of T-cell proliferation and induced cell death were observed even as the treated T cells produced high levels of interferon-gamma (IFN-γ). The inhibitory effects of MIF were partially reversed when lymphocytes from IFN-γ knockout mice were tested. We propose that the high levels of MIF produced by neuroblastoma cause activation induced T-cell death through an IFN-γ pathway and may eliminate activated T cells from the tumor microenvironment and thus contribute to escape from immune surveillance.

Original languageEnglish (US)
Pages (from-to)188-198
Number of pages11
JournalCytokine
Volume33
Issue number4
DOIs
StatePublished - Feb 21 2006

Keywords

  • Cell activation
  • Cytokines
  • Migration inhibitory factor
  • T cells
  • Tumor immunity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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