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Tumor-derived macrophage migration inhibitory factor (MIF) inhibits T lymphocyte activation. Cytokine 2006 Feb 21;33(4):188-98

Date

03/09/2006

Pubmed ID

16522371

Pubmed Central ID

PMC2018658

DOI

10.1016/j.cyto.2006.01.006

Scopus ID

2-s2.0-33646468680   26 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-gamma). The inhibitory effects of MIF were partially reversed when lymphocytes from IFN-gamma knockout mice were tested. We propose that the high levels of MIF produced by neuroblastoma cause activation induced T-cell death through an IFN-gamma pathway and may eliminate activated T cells from the tumor microenvironment and thus contribute to escape from immune surveillance.

Author List

Yan X, Orentas RJ, Johnson BD

Author

Bryon D. Johnson PhD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Death
Cell Line, Tumor
Cells, Cultured
Humans
Interferon-gamma
Interleukin-15
Interleukin-2
Lymphocyte Activation
Macrophage Migration-Inhibitory Factors
Mice
Mice, Inbred Strains
Mice, Knockout
Neoplasms
RNA, Small Interfering
T-Lymphocytes
jenkins-FCD Prod-399 190a069c593fb5498b7fcd942f44b7bc9cdc7ea1