RESEARCH ARTICLE
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.
Citation: Gooden MJM, Wiersma VR, Samplonius DF, Gerssen J, van Ginkel RJ, et al. (2013) Galectin-9 Activates and Expands Human T-Helper 1 Cells. PLoS ONE 8(5): e65616. doi:10.1371/journal.pone.0065616
Editor: Kjetil Tasken, University of Oslo, Norway
Received: February 19, 2013; Accepted: April 25, 2013; Published: May 31, 2013
Copyright: © 2013 Gooden et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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.
Competing interests: The authors have the following interests: Drs. Niki and Hirashima are board members of GalPharma Co., Ltd. The authors have a product in development: stable-form galectin-9. Name of the patent: NOVEL MODIFIED GALECTIN 9 PROTEINS AND USE THEREOF. Patent numbers: EP1736541, JP4792390, US8268324. There are no further patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
¶ These authors also contributed equally to this work.
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