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-1-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.