MHC class II, antigen presentation and tumor necrosis factor in renal tubular epithelial cells.
Proximal tubular (PT) epithelial cells express MHC class II (Ia) antigens in immunologically-mediated renal injury. To study the role of PT as accessory cells, we generated several murine PT-like epithelial cell lines by transformation with origin-defective SV40 DNA. These transformed cell lines display typical alkaline phosphatase and gamma-glutamyl-transpeptidase enzyme activity, proliferation to epidermal growth factor (EGF) and sodium-dependent glucose uptake. Clonal lines of transformed tubular cells from both normal C3H/FeJ and autoimmune MRL-lpr mice do not constitutively express Ia antigens or mRNA for class II. However, stimulation with recombinant interferon-gamma(rIFN-gamma) induces Ia mRNA and surface product in the cell lines. These Ia-positive cells can process and present hen egg-white lysozyme (HEL) to antigen-specific Iak-restricted T cell hybrids. Unstimulated tubular cells do not express detectable IL-1 alpha, IL-1 beta, TNA-alpha, or IL-6 mRNA. However, stimulation with IL-1 alpha or LPS induces TNF-alpha transcripts. We conclude that these cell lines have characteristics most consistent with a proximal tubular origin. They also bear characteristics of accessory cells such as processing and presentation of antigen and TNF-alpha gene expression. We speculate that PT have the capacity to participate in the pathogenesis of immune renal injury.
Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
R P
RP
Wuthrich
L H
LH
Glimcher
M A
MA
Yui
A M
AM
Jevnikar
S E
SE
Dumas
V E
VE
Kelley
D002460:Cell Line; D002472:Cell Transformation, Viral; D002999:Clone Cells; D004847:Epithelial Cells; D004848:Epithelium / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression; D000949:Histocompatibility Antigens Class II / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007684:Kidney Tubules / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000949:Histocompatibility Antigens Class II; D014409:Tumor Necrosis Factor-alpha