title: IFN-gamma and LPS differentially modulate class II MHC and B7-1 expression on murine renal tubular epithelial cells.
abstract: BACKGROUND
  We have investigated inducible class II major histocompatibility complex (MHC) and B7 expression on primary murine renal tubular epithelial cells, called F1K cells, and examined their role in activating nephritogenic T cells derived from kidneys of animals with autoimmune glomerulonephritis.
  
  
  METHODS
  Class II MHC, class II transactivator, and costimulatory molecule expression were evaluated in untreated and cytokine-treated F1K cells by Northern hybridization and flow cytometry. Cell-surface B7-1 expression was evaluated in vitro by immunoprecipitation and in vivo by immunohistochemistry. T-cell activation studies were then performed to assess the functional significance of B7-1 expression on F1K cells.
  
  
  RESULTS
  Coincubation of F1K cells with interferon (IFN)-gamma and lipopolysaccharide (LPS) significantly decreased IFN-gamma-induced class II MHC expression, by both fluorescence-activated cell sorting and Northern analyses. LPS-mediated inhibition of class II MHC in this setting was effected through a decrease in class II transactivator mRNA levels in treated F1K cells. By contrast, IFN-gamma and LPS coincubation induced B7-1 but not B7-2 expression in F1K cells, as detected by Northern analysis, flow cytometry, and immunoprecipitation. In addition, renal tubular staining for B7-1 was apparent in kidneys isolated from IFN-gamma+LPS-treated recipient mice, as well as mice with autoimmune glomerulonephritis. Further studies evaluated the interaction of F1K cells and MR1.3, a nephritogenic CD4+ Th2 clone derived from kidneys of animals with autoimmune glomerulonephritis. Cytokine production assays revealed that F1K cells activated MR1.3 cells if they were pretreated with both IFN-gamma and LPS 48 hours prior to exposure to nephritogenic T cells.
  
  
  CONCLUSIONS
  These studies are the first description of a differential regulation of class II MHC and B7-1 expression in renal tubular epithelial cells mediated by IFN-gamma and LPS. Such findings indicate that discrete proinflammatory stimuli could potentiate antigen-presenting capabilities of renal tubular epithelial cells in vivo and further suggest a direct role of such nonprofessional antigen-presenting cells in modulating renal immune responses.
authors.affiliation: University of Pennsylvania School of Medicine, Department of Medicine, Renal-Electrolyte and Hypertension Division, Philadelphia, PA, USA.
authors.forename: N
authors.initials: N
authors.lastname: Banu
authors.forename: C M
authors.initials: CM
authors.lastname: Meyers
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D018122:B7-1 Antigen / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000276:immunology / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology*; D007684:Kidney Tubules / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D018122:B7-1 Antigen; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D007371:Interferon-gamma