title: MHC expression kinetics and immunogenicity of mesenchymal stromal cells after short-term IFN-gamma challenge.
abstract: OBJECTIVE
  Under the influence of interferon-gamma (IFN-gamma), mesenchymal stromal cells (MSCs) are conditional antigen-presenting cells, which have immunosuppressive potential. Apart from IFN-gamma 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-gamma in different clinical scenarios.
  
  
  METHODS
  Here, we demonstrated that IFN-gamma-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-gamma 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-gamma treatment for 8 days. High-dose IFN-gamma-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-gamma effects will adversely affect the immunoprivilege status and lifespan of MSCs.
authors: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
authors: Wing Keung
authors: WK
authors: Chan
authors: Allan Sik-Yin
authors: AS
authors: Lau
authors: James Chun-Bong
authors: JC
authors: Li
authors: Helen Ka-Wai
authors: HK
authors: Law
authors: Yu Lung
authors: YL
authors: Lau
authors: Godfrey Chi-Fung
authors: GC
authors: Chan
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D000949:Histocompatibility Antigens Class II / Q000032:analysis*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D008213:Lymphocyte Activation; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma