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

Background. We have investigated inducible class II major histocompatibilit y complex (MHC) and B7 expression on primary murine renal tubular epithelia l cells, called F1K cells, and examined their role in activating nephritoge nic T cells derived from kidneys of animals with autoimmune glomerulonephri tis. Methods. Class II MHC, class II transactivator, and costimulatory molecule expression were evaluated in untreated and cytokine-treated F1K cells by No rthern hybridization and flow cytometry. Cell-surface B7-1 expression was e valuated in vitro by immunoprecipitation and in vivo by immunohistochemistr y. T-cell activation studies were then performed to assess the functional s ignificance of B7-1 expression on F1K cells. Results. Coincubation of F1K cells with interferon (IFN)-gamma and lipopoly saccharide (LPS) significantly decreased IFN-gamma-induced class II MHC exp ression, by both fluorescence-activated cell sorting and Northern analyses. LPS-mediated inhibition of class II MHC in this setting was effected throu gh 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 expre ssion in F1K cells, as detected by Northern analysis, flow cytometry, and i mmunoprecipitation. In addition, renal tubular staining for B7-1 was appare nt 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 derive d from kidneys of animals with autoimmune glomerulonephritis. Cytokine prod uction assays revealed that F1K cells activated MR1.3 cells if they were pr etreated with both IFN-gamma and LPS 48 hours prior to exposure to nephrito genic T cells. Conclusions. These studies are the first description of a differential regu lation of class II MHC and B7-1 expression in renal tubular epithelial cell s mediated by IFN-gamma and LPS. Such findings indicate that discrete proin flammatory stimuli could potentiate antigen-presenting capabilities of rena l tubular epithelial cells in vivo and further suggest a direct role of suc h nonprofessional antigen-presenting cells in modulating renal immune respo nses.