Cultured rat kidney parenchymal components are damaged by cytotoxic lymphocytes produced in MLC

Donor-specific cytotoxic lymphocytes (CTL) can be recovered from rejecting allografts both in animal models and in humans. These allograft infiltrating CTL expressing specific cytotoxicity to relevant MHC-restricted target cells in vitro most likely constitute the major effector arm during rejection. Effector cells with similar phenotype, specificity and function can be produced in mixed lymphocyte cultures (MLC). Despite the pivotal importance of CTL in allograft rejection, there is limited information about the susceptibility of different parenchymal graft cells to CTL-mediated damage. We used cultured rat glomerular epithelial cells (GEPC), glomerular mesangial cells (GMC), tubular cells (TC) and heart endothelial cells (HEC) as distinct parenchymal target components in 4 h Chromium release assays. All of these graft components were damaged by CTL produced in 6-day MLC (specific release: 10-25%). Three-day gamma-interferon (IFN-G) treatment enhanced MHC class I and II surface expression on all our targets and increased their susceptibility for CTL-mediated lysis in our experiments (specific release: 20-60%).