IFN-gamma and LPS differentially modulate class II MHC and B7-1 expression on murine renal tubular epithelial cells

Kidney Int. 1999 Jun;55(6):2250-63. doi: 10.1046/j.1523-1755.1999.00495.x.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology
  • B7-1 Antigen / metabolism*
  • Cells, Cultured
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology
  • Female
  • Graft vs Host Disease / immunology
  • Graft vs Host Disease / pathology
  • Histocompatibility Antigens Class II / metabolism*
  • Immunohistochemistry
  • Interferon-gamma / pharmacology*
  • Kidney Tubules / cytology
  • Kidney Tubules / drug effects*
  • Kidney Tubules / immunology*
  • Lipopolysaccharides / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred DBA
  • Recombinant Proteins
  • T-Lymphocytes / immunology


  • B7-1 Antigen
  • Histocompatibility Antigens Class II
  • Lipopolysaccharides
  • Recombinant Proteins
  • Interferon-gamma