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- Title
Analysis of T cell lines from rejecting renal allografts.
- Authors
Yard, Benito A.; Kooymans-Couthino, Mariska; Reterink, Thomas; Van Den Elsen, Peter; Paape, Marion E.; Bruyn, Jan Antony; van Es, Leendert A.; Daha, Mohammed R.; Van Der Woude, Fokko J.
- Abstract
Acute rejection after renal allotransplantation is characterised by the presence of a mononuclear cell infiltrate in the interstitium with involvement of tubuli. In a previous study on renal histology we showed that tubular damage by graft infiltrating cells (GIC) is a sign of clinically significant rejection. We cultured proximal tubular epithelial ceils (PTEC) and T cells bearing the interleukin 2 (IL-2) receptor from biopsies after transplantation. In vitro outgrowth of T cells from the biopsy was significantly (P = 0.0014) related to histological signs of graft rejection. Of the T cell lines generated from 25 biopsies, only five lines showed no or low cytotoxicity against donor PTEC. Three cell lines were cytotoxic towards donor PTEC, but not against PHA stimulated donor splenocytes. suggesting tissue specificity of GIC. Treatment of PTEC with interferon (IFN) gamma for 72 hours to upregulate MHC class I and to induce MHC class II expression did not necessarily result in an increased susceptibility to lysis. However, three PTEC lines displayed an increment of susceptibility to lysis after IFN gamma treatment. Analysis of one T cell line from the same graft revealed a high percentage of CD4 positive cells, compatible with a class II restricted cytotoxicity. This was confirmed by blocking experiments using anti- CD4, anti-CD8. anti-class I, and anti-class II antibodies. Blocking experiments were done with 12 of these 25 lines. Anti-CD3 and anti-CD18 antibodies inhibited cytotoxicity in every case, showing that cytotoxicity was T cell mediated. The T cell lines generated from renal biopsies exhibited an oligo- or polyclonal character as determined by TCR Vβ gene usage by semi-quantitative PCR. but only three T cell lines showed a clear Vβ gene dominance. Oligoclonality of the T cell lines was not specifically associated with a well matched graft or a short time interval between transplantation and biopsy. Our results show (hat (he outgrowth of IL-2 dependent T cells from a biopsy correlated with (he occurrence of rejection. Outgrowing T cells may be oligoclonal or polyclonal. The in vitro lysis of PTEC is donor- and sometimes tissue-specific.
- Subjects
T cells; CELL lines; KIDNEY transplantation; HOMOGRAFTS; GRAFT rejection; EPITHELIAL cells; KIDNEY tubules
- Publication
Kidney International Supplement, 1993, Issue 39, pS-133
- ISSN
0098-6577
- Publication type
Article
- DOI
10.1111/1523-1755.ep15009057