title: Galectin-9 activates and expands human T-helper 1 cells.
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.
authors.affiliation: Department of Surgery, Translational Surgical Oncology, University Medical Center Groningen (UMCG), University of Groningen, Groningen, The Netherlands.
authors.forename: Marloes J M
authors.initials: MJ
authors.lastname: Gooden
authors.forename: Valerie R
authors.initials: VR
authors.lastname: Wiersma
authors.forename: Douwe F
authors.initials: DF
authors.lastname: Samplonius
authors.forename: Jurjen
authors.initials: J
authors.lastname: Gerssen
authors.forename: Robert J
authors.initials: RJ
authors.lastname: van Ginkel
authors.forename: Hans W
authors.initials: HW
authors.lastname: Nijman
authors.forename: Mitsuomi
authors.initials: M
authors.lastname: Hirashima
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Paul
authors.initials: P
authors.lastname: Eggleton
authors.forename: Wijnand
authors.initials: W
authors.lastname: Helfrich
authors.forename: Edwin
authors.initials: E
authors.lastname: Bremer
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D037161:Galectins / Q000494:pharmacology*; D000072597:Hepatitis A Virus Cellular Receptor 2; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D010641:Phenotype; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D037161:Galectins; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; C105032:LGALS9 protein, human; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell