MHC expression kinetics and immunogenicity of mesenchymal stromal cells after short-term IFN-gamma challenge.
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.
Chan
Wing Keung
WK
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong.
Lau
Allan Sik-Yin
AS
Li
James Chun-Bong
JC
Law
Helen Ka-Wai
HK
Lau
Yu Lung
YL
Chan
Godfrey Chi-Fung
GC
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
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma