Tissue-specific characteristics of cytotoxic graft-infiltrating T cells during renal allograft rejection

Background. The alloresponse after renal transplantation was studied using alloreactive T cells generated in vivo (from renal biopsies) and in vitro (from mixed kidney lymphocyte cultures). Methods. Tissue specificity of graft-infiltrating T cells (GIC) was investigated using donor-derived proximal tubular epithelial cells (PTEC) and splenocytes as targets in cytotoxicity assays. Results. The outgrowth of cytotoxic T cells was associated with histologically proven interstitial rejection. GIC were categorized into four groups: (1) GIC cytotoxic for both PTEC and splenocytes (n=30), (2) noncytotoxic GIC (n=8), (3) GIC recognizing only splenocytes (n=1), and (4) GIC specifically recognizing PTEC (n=7). Similar tissue-specific T cells could be generated in vitro using mixed kidney lymphocyte cultures. Cytotoxicity of GIC from biopsies with moderate to severe rejection was CD8 independent, whereas cytotoxicity toward splenocytes was CD8 dependent. Conclusions. Our results show that polyclonal cytotoxic T-cell responses with tissue-specific characteristics are elicited during rejection episodes after renal transplantation.