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 language | English (US) |
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Pages (from-to) | 188-198 |
Number of pages | 11 |
Journal | Cytokine |
Volume | 33 |
Issue number | 4 |
DOIs | |
State | Published - 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