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IFN-gamma and LPS differentially modulate class II MHC and B7-1 expression on murine renal tubular epithelial cells
1University of Pennsylvania School of Medicine, Department of Medicine, Renal-Electrolyte and Hypertension Division, Philadelphia, PA, USA.
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.