MHC expression kinetics and immunogenicity of mesenchymal stromal cells after short-term IFN-gamma challenge.
Exp Hematol
; 36(11): 1545-55, 2008 Nov.
Article
en En
| MEDLINE
| ID: mdl-18715686
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. MATERIALS ANDMETHODS:
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.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antígenos de Histocompatibilidad Clase I
/
Antígenos de Histocompatibilidad Clase II
/
Interferón gamma
/
Células Madre Mesenquimatosas
Límite:
Humans
Idioma:
En
Revista:
Exp Hematol
Año:
2008
Tipo del documento:
Article
País de afiliación:
Hong Kong