Journal
PLOS ONE
Volume 8, Issue 5, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0065616
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Funding
- Dutch Cancer Society [RUG 2009-4355, RUG2009-4542/RUG2011-5206, RUG2007-3784]
- Netherlands Organization for Scientific Research
- Melanoma Research Alliance
- Alexander von Humboldt Foundation
- European Community's Seventh Framework Programme (FP7) [215009]
- Grants-in-Aid for Scientific Research [25460592] Funding Source: KAKEN
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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.
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