MHC expression kinetics and immunogenicity of mesenchymal stromal cells after short-term IFN-γ challenge
Received 14 February 2008; received in revised form 9 June 2008; accepted 17 June 2008. published online 21 August 2008.
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.
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China
Offprint requests to: Godfrey Chi-Fung Chan, M.D., Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, 102 Pokfulam Road, The University of Hong Kong, HKSAR, China
ABSTRACT