Abstract
Galectin-9 (Gal-9) is known for induction of apoptosis in IFN-γ and IL-17 producing T-cells and amelioration of autoimmunity in murine models. On the other hand, Gal-9 induced IFN-γ positive T-cells in a sarcoma mouse model and in food allergy, suggesting that Gal-9 can have diametric effects on T-cell immunity. Here, we aimed to delineate the immunomodulatory effect of Gal-9 on human resting and ex vivo activated peripheral blood lymphocytes. Treatment of resting lymphocytes with low concentrations of Gal-9 (5-30 nM) induced apoptosis in ∼60% of T-cells after 1 day, but activated the surviving T-cells. These viable T-cells started to expand after 4 days with up to 6 cell divisions by day 7 and an associated shift from naïve towards central memory and IFN-γ producing phenotype. In the presence of T-cell activation signals (anti-CD3/IL-2) Gal-9 did not induce T-cell expansion, but shifted the CD4/CD8 balance towards a CD4-dominated T-cell response. Thus, Gal-9 activates resting T-cells in the absence of typical T-cell activating signals and promotes their transition to a TH1/C1 phenotype. In the presence of T-cell activating signals T-cell immunity is directed towards a CD4-driven response by Gal-9. Thus, Gal-9 may specifically enhance reactive immunological memory.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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CD4-Positive T-Lymphocytes / cytology
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / metabolism
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Cell Death / drug effects
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Dose-Response Relationship, Drug
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Galectins / pharmacology*
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Hepatitis A Virus Cellular Receptor 2
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Humans
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Immunologic Memory / drug effects
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / metabolism
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Lymphocyte Activation / drug effects*
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Membrane Proteins / metabolism
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Phenotype
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Receptors, Antigen, T-Cell / metabolism
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T-Lymphocytes, Helper-Inducer / cytology
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T-Lymphocytes, Helper-Inducer / drug effects*
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T-Lymphocytes, Helper-Inducer / metabolism
Substances
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Galectins
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HAVCR2 protein, human
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Hepatitis A Virus Cellular Receptor 2
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LGALS9 protein, human
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Membrane Proteins
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Receptors, Antigen, T-Cell
Grants and funding
This work was supported by Dutch Cancer Society grants RUG 2009-4355 (E.B.), RUG2009-4542/RUG2011-5206 (E.B/W.H.) and RUG2007-3784 (W.H.), the Netherlands Organization for Scientific Research (E.B.), the Melanoma Research Alliance (E.B.), the Alexander von Humboldt Foundation (E.B.) and the European Community’s Seventh Framework Programme (FP7/2007–2013) under grant agreement (grant number 215009) (P.E.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.