Yard B A, Claas F H, Paape M E, Bruijn J A, Daha M R, van Es L A, van der Woude F J
Department of Nephrology, University Hospital Leiden, The Netherlands.
Nephrol Dial Transplant. 1994;9(7):805-10.
Acute interstitial rejection is an important clinical problem after cadaver kidney transplantation. Recently we have reported that six of 17 graft-infiltrating cell (GIC) lines isolated from kidneys undergoing such rejection episodes recognize graft-derived proximal tubular cells but not lymphoid cells from the same donor. In this study we characterized the specificity of one such GIC line in more detail. From this T-cell line, 18 cytotoxic T-cell (CTL) clones were isolated. Four of these were also cytotoxic against donor lymphoid cells. Nine tissue-specific clones were selected for further analysis. They all contained CD8+ and TCR alpha/beta+ cells and cytotoxicity by these cells was class I restricted. Only proximal tubular epithelial cells (PTEC) expressing HLA-A31 (an antigen present in the donor but absent in the recipient) were recognized by all clones. There were, however, three clones that did not lyse all HLA-A31+ PTEC lines, demonstrating recognition of an HLA-A31 tissue-associated polymorphism. Thus during rejection episodes after renal transplantation GIC may recognize various tissue-derived peptides bound to a mismatched HLA molecule on the cell surface of renal parenchymal cells. These GIC are likely to contribute to the observed destruction of tubuli during episodes of acute rejection after kidney transplantation.
急性间质性排斥反应是尸体肾移植后一个重要的临床问题。最近我们报道，从经历此类排斥反应的肾脏中分离出的17个移植物浸润细胞（GIC）系中有6个可识别移植物来源的近端肾小管细胞，但不能识别来自同一供体的淋巴细胞。在本研究中，我们更详细地描述了其中一个GIC系的特异性。从这个T细胞系中，分离出18个细胞毒性T细胞（CTL）克隆。其中4个对供体淋巴细胞也具有细胞毒性。选择了9个组织特异性克隆进行进一步分析。它们均含有CD8 +和TCRα/β +细胞，并且这些细胞的细胞毒性受I类分子限制。只有表达HLA - A31（供体中存在但受体中不存在的一种抗原）的近端肾小管上皮细胞（PTEC）能被所有克隆识别。然而，有3个克隆不能裂解所有HLA - A31 + PTEC系，这表明它们识别的是一种HLA - A31组织相关多态性。因此，在肾移植后的排斥反应期间，GIC可能识别与肾实质细胞表面错配的HLA分子结合的各种组织来源的肽段。这些GIC可能在肾移植后急性排斥反应期间导致观察到的肾小管破坏。
