MHC expression kinetics and immunogenicity of mesenchymal stromal cells after short-term IFN-γ challenge

Objective: Under the influence of interferon-γ (IFN-γ), mesenchymal stromal cells (MSCs) are conditional antigen-presenting cells, which have immunosuppressive potential. Apart from IFN-γ upregulation of major histocompatibility complexes class I and II (MHC-I and MHC-II) expression, the underlying kinetics and mechanisms have not been described previously. This information is helpful to delineate how human MSCs can be modulated by IFN-γ in different clinical scenarios. Materials and Methods: Here, we demonstrated that IFN-γ-treated MSCs underwent classical signal transduction pathway via phosphorylation of signal transducers and activators of transcription-1, activation of interferon regulatory factor-1, and class II transactivator comparable to that of primary human blood macrophages. Results: IFN-γ markedly induced expression of MHC-I instantly, while its effects on MHC-II were less dramatic and delayed up to 4 days. This is due to a slower intracellular transport of the MHC-II antigen to the membrane surface. More important is that MSCs showed a reduction in their proliferation by 50% without evidence of cell death after prolonged IFN-γ treatment for 8 days. High-dose IFN-γ-treated MSCs (500 U/mL) could initiate T-cell activation as indicated by expression of CD25 and proliferation of allogeneic T cells. Conclusions: The summative IFN-γ effects will adversely affect the immunoprivilege status and lifespan of MSCs.