Skip to main content

Volume 9 Supplement 2

AIDS Vaccine 2012

Tim-3-mediated signaling in NK cells may be modulated by increased Galectin-9 expression in HIV-1 infection


Natural Killer (NK) cells constitutively express high levels of Tim-3, an immunoregulatory molecule recently proposed to be a marker for mature and fully functional NK cells (Ndhlovu et al., 2012). Cytokines can induce Tim-3 expression on NK cells, and IFN-gamma production by Tim-3+ NK cells can be enhanced by exposure to Galectin-9 (Gleason et al. 2012), yet their ability to kill target cells is lost upon Tim-3 cross-linking. Moreover, up-regulation of Tim-3 on NK cells has been associated with reduced anti-viral properties in chronic hepatitis B infection (Ju et al., 2010). However, the impact of HIV-1 infection on Tim-3 expression on NK cells and on Tim-3-mediated NK cell function has not been studied yet.


Flow cytometry was used to analyze Tim-3 and intracellular galectin-9 expression in subjects with acute and chronic HIV-1 infection, in HIV-1 elite (VL <50 copies/ml) and viremic controllers (VL <2000 copies/ml), and in HIV-1 negative subjects. Plasma levels of Galectin-9 were quantified by ELISA.


HIV-1 infection was associated with reduced expression of Tim-3 on NK cells, as early as in acute infection, and could be normalized by HAART. Importantly, percentages of Tim-3+ CD56dim NK cells correlated with CD4+ cell counts in untreated patients. Plasma concentrations of Galectin-9 were higher in HIV-1-infected individuals than in controls. Interestingly, Galectin-9 expression in immune cells was significantly elevated in acute infection, with monocytes and dendritic cells displaying the highest levels, which correlated with viral loads. In vitro, Galectin-9 triggered NK cell activation and Tim-3 down-regulation on NK cells.


Further investigations are warranted to determine whether increased Galectin-9 production alters Tim-3 function and contributes to NK cell impaired activity in chronic HIV-1 infection. Defining the role of NK cell receptors in the control of HIV-1 will offer novel therapeutic targets to manipulate and improve future HIV-1 vaccine strategies.

Author information

Authors and Affiliations


Rights and permissions

This article is published under license to BioMed Central Ltd. 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 work is properly cited.

Reprints and Permissions

About this article

Cite this article

Jost, S., Moreno-Nieves, U., Garcia Beltran, W. et al. Tim-3-mediated signaling in NK cells may be modulated by increased Galectin-9 expression in HIV-1 infection. Retrovirology 9 (Suppl 2), P173 (2012).

Download citation

  • Published:

  • DOI:


  • Natural Killer Cell
  • Natural Killer Cell Function
  • Natural Killer Cell Receptor
  • Kill Target Cell
  • CD56dim Natural Killer Cell