MHC class II upregulation and colocalization with Fas in experimental models of immune-mediated bone marrow failure.
Exp Hematol
; 39(8): 837-49, 2011 Aug.
Article
em En
| MEDLINE
| ID: mdl-21635935
OBJECTIVE: To test the hypothesis that γ-interferon (IFN-γ) promotes major histocompatibility complex (MHC) class II expression on bone marrow (BM) cell targets that facilitate T-cell-mediated BM destruction in immune-mediated BM failure. MATERIALS AND METHODS: Allogeneic lymph node (LN) cells were infused into MHC- or minor histocompatibility antigen-mismatched hosts to induce BM failure. MHC class II and Fas expression and cell apoptosis were analyzed by flow cytometry. MHC class II-Fas colocalization was detected by ImageStream Imaging Flow Cytometry and other cell-to-cell associations were visualized by confocal microscopy. T-cell-mediated BM cell apoptosis and effects of IFN-γ on MHC class II-Fas colocalization on normal BM cells were studied using cell culture in vitro followed by conventional and imaging flow cytometry. RESULTS: BM failure animals had significantly upregulated MHC class II expression on CD4(-)CD8(-)CD11b(-)CD45R(-) residual BM cells and significantly increased MHC class II-Fas colocalization on BM CD150(+) and CD34(+) hematopoietic cells. MHC class II(+)Fas(+) BM cells were closely associated with CD4(+) T cells in the BM of affected animals, and they were significantly more responsive to T-cell-mediated cell apoptosis relative to MHC class II(-)Fas(-) BM cells. Infusion of IFN-γ-deficient LN cells into minor histocompatibility antigen-mismatched recipients resulted in no MHC class II-Fas upregulation and no clinically overt BM failure. Treatment with recombinant IFN-γ significantly increased both MHC class II-Fas coexpression and colocalization on normal BM cells. CONCLUSIONS: Elevation of the inflammatory cytokine IFN-γ-stimulated MHC class II expression and MHC class II-Fas colocalization, which may facilitate T-cell-mediated cell destruction.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças da Medula Óssea
/
Linfócitos T
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Antígenos de Histocompatibilidade Classe II
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Receptor fas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article