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Epithelial- and endothelial-cell specificity of renal graft infiltrating T cells
J G Deckers1, M R Daha, S W Van der Kooij
1Department of Nephrology, Leiden University Medical Center, The Netherlands.
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.
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.