Galectin-9 Activates and Expands Human T-Helper 1 Cells

Marloes J. M. Gooden, Valerie R. Wiersma, Douwe F. Samplonius, Jurjen Gerssen, Robert J. van Ginkel, Hans W. Nijman, Mitsuomi Hirashima, Toshiro Niki, Paul Eggleton, Wijnand Helfrich, Edwin Bremer*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Galectin-9 (Gal-9) is known for induction of apoptosis in IFN-gamma and IL-17 producing T-cells and amelioration of autoimmunity in murine models. On the other hand, Gal-9 induced IFN-gamma 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 similar to 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 naive towards central memory and IFN-gamma 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 T-H1/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.

Original languageEnglish
Article numbere65616
Number of pages11
JournalPLoS ONE
Volume8
Issue number5
DOIs
Publication statusPublished - 31-May-2013

Keywords

  • REGULATORY T-CELLS
  • ANTITUMOR IMMUNITY
  • DENDRITIC CELLS
  • BINDING LECTIN
  • TIM-3
  • SUPPRESSES
  • MICE
  • INFECTION
  • APOPTOSIS
  • ARTHRITIS

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