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Modulation of human monocytes by Escherichia coli heat‐labile enterotoxin B‐subunit; altered cytokine production and its functional consequences
Author(s) -
Turcanu Victor,
Hirst Timothy R.,
Williams Neil A.
Publication year - 2002
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2002.01429.x
Subject(s) - heat labile enterotoxin , cytokine , t cell , monocyte , enterotoxin , biology , immunology , microbiology and biotechnology , immune system , escherichia coli , biochemistry , gene
Summary In murine systems, the B subunit of Escherichia coli heat‐labile enterotoxin (EtxB) is a potent immunomodulator capable of suppressing Th1‐mediated autoimmune diseases. This results from its ability to bind cell surface receptors, principally GM1‐ganglioside, and as a consequence down‐regulate the pathological T helper type 1 (Th1) response. The capacity of EtxB to alter human T‐cell responses has not been investigated. Here we show that EtxB, but not the receptor non‐binding mutant EtxB (G33D), triggers the release of interleukin (IL)‐10, IL‐6 and tumour necrosis factor‐α (TNF‐α) by human monocytes. The production of IL‐8, transforming growth factor‐β (TGF‐β) or IL‐12 was not enhanced by EtxB. Indeed, EtxB was shown to inhibit IL‐12 secretion in monocytes stimulated with interferon‐γ (IFN‐γ) and lipopolysaccharide (LPS) by an IL‐10‐independent mechanism. When EtxB‐treated monocytes were used as antigen presenting cells in an allogeneic mixed lymphocyte reaction (MLR), IL‐10 and IFN‐γ production were increased in comparison to levels seen in cultures stimulated with untreated monocytes; proliferation was unaltered. This modulation of the T‐cell response was not only evident in the primary MLR triggered by EtxB‐treated monocytes, but also upon restimulation of the responding T cells with fresh untreated monocytes; indicating that presentation by EtxB‐treated monocytes leads to altered T‐cell differentiation. Sorting experiments showed that IL‐10 secreting T cells from the MLR cultures were strong suppressors of T‐cell proliferation following their addition into a fresh primary MLR.