However, mediators responsible for ameliorating respiratory viral-induced lung injuries remain unclear. In animal models, influenza H9N2 viral infection increases serum and lung chemokines responsible for lung leukocyte infiltration, including granulocyte–macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1 alpha (MIP-1α) and others, which are markedly reduced by intravenous administration of MSCs [16]. Increased levels of IFN-γ, typical of antiviral immune responses, alone or together with other pro-inflammatory cytokines, prompt MSC activation including the release of anti-inflammatory mediators. The importance of such IFN “licensing” of immunomodulating effects has been previously demonstrated in a model of graft versus host disease (GVHD), where the MSC-treated recipients of IFN-γ−/− T-cell grafts did not respond to cell therapy, evolving into fatal GVHD [17]. Unpublished data from COVID-19 patients in Italy suggest that high levels of IFN-γ are found and thus may influence systemically administered MSCs (Massimo Dominici, University Hospital of Modena and Reggio Emilia, Modena, Italy; personal communication). However, “licensed” MSCs can also suppress alloantigen-induced T-cell functions in vitro, potentially compromising antiviral responses needed for disease control. For example, MSCs suppress lymphocyte proliferation in response to the activation of influenza-specific T-cells in vitro [18]. Umbilical cord-derived MSCs (UC-MSCs) have also been shown to inhibit the cytotoxicity of specific T-cells against H1N1 influenza virus in vitro [19], leading perhaps to prolonged infection in recipients. This is in contrast to reports where, for example, in models of cytomegalovirus (CMV) infection, MSCs exert differential effects on alloantigen and virus-specific T-cells that retain the ability to proliferate, produce IFN-γ and kill CMV-infected cells in vitro [20].