GRAFT-INFILTRATING CELLS CAN RECOGNIZE TISSUE-SPECIFIC ANTIGENS ON PROXIMAL TUBULAR EPITHELIAL-CELLS DURING ACUTE RENAL-ALLOGRAFT REJECTION

The immune response during renal allograft rejection may be directed a gainst renal-specific antigens. We conducted a study to demonstrate ti ssue-specific recognition of proximal tubular epithelial cells (PTEC) by graft-infiltrating cells (GIC). Both PTEC and GIC were isolated fro m the same biopsy. Of the T cell lines generated from 25 biopsies only 5 lines showed no or low cytotoxicity against donor PTEC. Three lines were cytotoxic towards donor PTEC, but not against PHA-stimulated spl enocytes, suggesting tissue specificity of GIC. To study the tissue sp ecificity more in detail we performed a limiting dilution of one of th e tissue-specific GIC lines. We obtained 18 cytotoxic T cell (CTL) clo nes, five of these clones were cytotoxic against donor PHA blasts, dem onstrating not only the polyclonal nature of the T cell line, but also that tissue specificity was not due to an intrinsic non-susceptibilit y of PHA blasts. Nine tissue-specific clones were selected for further analysis. All tissue-specific clones were CD8(+) and T cell receptor (TCR) alpha/beta(+). Cytotoxicity of all clones could be inhibited wit h CD3, CD8, anti-MHC class I and CD18 monoclonal antibody (MoAb). Only PTEC expressing HLA-A31 were recognized by these clones. However, the re were three clones that did not lyse all HLA-A31-expressing PTEC lin es, suggesting recognition of a HLA-A31, tissue-associated polymorphis m. These results show for the first time that human renal-specific ant igens may be recognized by GIC in vitro. These GIC are likely to contr ibute to the observed destruction of tubuli during episodes of acue re jection.