Journal
CYTOTHERAPY
Volume 18, Issue 3, Pages 360-370Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.jcyt.2015.12.004
Keywords
apoptosis; delayed type hypersensitivity; galectin-1; immunosuppression; mesenchymal stromal cells; type I diabetes
Categories
Funding
- Hungarian Scientific Research Fund (OTKA) [PD75938]
- Janos Bolyai Research Fellowship of the Hungarian Academy of Sciences
- Hungarian Academy of Sciences Lendulet [LP2014-7/2014]
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Background aims. Mesenchymal stromal cells (MSCs) have powerful immunosuppressive activity. This function of MSCs is attributed to plethora of the expressed immunosuppressive factors, such as galectin-1 (Gal-1), a pleiotropic lectin with robust anti-inflammatory effect. Nevertheless, whether Gal-1 renders or contributes to the immunosuppressive effect of MSCs has not been clearly established. Therefore, this question was the focus of a complex study. Methods. MSCs were isolated from bone marrows of wild-type and Gal-1 knockout mice and their in vitro anti-proliferative and apoptosis-inducing effects on activated T cells were examined. The in vivo immunosuppressive activity was tested in murine models of type I diabetes and delayed-type hypersensitivity. Results. Both Gal-l-expressing and-deficient MSCs inhibited T-cell proliferation. Inhibition of T-cell proliferation by MSCs was mediated by nitric oxide but not PD-L1 or Gal-1. In contrast, MSC-derived Gal-1 triggered apoptosis in activated T cells that were directly coupled to MSCs, representing a low proportion of the T-cell population. Furthermore, absence of Gal-1 in MSCs did not affect their in vivo immunosuppressive effect. Conclusions. These results serve as evidence that Gal-1 does not play a role in the systemic immunosuppressive effect of MSCs. However, a local contribution of Gal-1 to modulation of T-cell response by direct cell-to-cell interaction cannot be excluded. Notably, this study serves a good model to understand how the specificity of a pleiotropic protein depends on the type and localization of the producing effector cell and its target.
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