title: MHC class II upregulation and colocalization with Fas in experimental models of immune-mediated bone marrow failure.
abstract: 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.
  
  
  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.
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1202, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Erie
authors.forename: Leigh
authors.initials: L
authors.lastname: Samsel
authors.forename: Tomoiku
authors.initials: T
authors.lastname: Takaku
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Desierto
authors.forename: Keyvan
authors.initials: K
authors.lastname: Keyvanfar
authors.forename: J Philip
authors.initials: JP
authors.lastname: McCoy
authors.forename: Neal S
authors.initials: NS
authors.lastname: Young
authors.forename: Jichun
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001855:Bone Marrow Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D019014:fas Receptor / Q000276:immunology* / Q000378:metabolism
chemical_list: D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D019014:fas Receptor; D007371:Interferon-gamma