Epithelial- and endothelial-cell specificity of renal graft infiltrating T cells.
Previously, we have shown that rejecting renal allografts are infiltrated by tissue-specific T cells that in vitro kill proximal tubular epithelial cells (PTEC), while donor-derived splenocytes are not affected. In the current unique study we assessed the reactivity of graft-infiltrating T cells (GIC) for three different donor-derived cell types. Cytotoxicity of GIC was tested against PTEC, as well as donor-derived gonadal vein endothelial cells (GOVEC) and splenocytes. T cells lysed PTEC, GOVEC and splenocytes expressing a mismatched donor HLA antigen, HLA-A29(19). Interestingly, PTEC and GOVEC, not splenocytes, expressing none of the donor HLA antigens were also killed. T cell clones, obtained by limiting dilution cloning of the GIC line, could be divided into different categories: clones recognizing both PTEC and GOVEC expressing the mismatched HLA-A29(19), clones recognizing either PTEC or GOVEC expressing the mismatched HLA-A29(19) and also clones specifically recognizing PTEC or GOVEC independent of donor HLA antigen expression. In conclusion, T cell clones with specificities for either epithelial or endothelial cells exist, leaving a role for tissue-specific antigens in allograft rejection.
Department of Nephrology, Leiden University Medical Center, The Netherlands.
J G
JG
Deckers
M R
MR
Daha
S W
SW
Van der Kooij
F J
FJ
Van der Woude
D000328:Adult; D000941:Antigens / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D004730:Endothelium, Vascular / Q000276:immunology / Q000473:pathology*; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology; D015234:HLA-A Antigens / Q000276:immunology; D006648:Histocompatibility / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology / Q000473:pathology*; D007687:Kidney Tubules, Proximal / Q000276:immunology / Q000473:pathology*; D013045:Species Specificity; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology; D014184:Transplantation, Homologous; D014680:Veins / Q000276:immunology / Q000473:pathology
D000941:Antigens; D017252:CD3 Complex; D015234:HLA-A Antigens; C035524:HLA-A29 antigen