End‐stage renal disease, dialysis, kidney transplantation and their impact on CD CD 4 + + T‐cell differentiation

摘要

Summary Premature aging of both CD 4 + regulatory T (Treg) and CD 4 + responder‐T (Tresp) cells in patients with end‐stage renal disease ( ESRD ) is expected to affect the success of later kidney transplantation. Both T‐cell populations are released from the thymus as inducible T‐cell co‐stimulator‐positive ( ICOS + ) and ICOS ? recent thymic emigrant ( RTE ) Treg/Tresp cells, which differ primarily in their proliferative capacities. In this study, we analysed the effect of ESRD and subsequent renal replacement therapies on the differentiation of ICOS + and ICOS ? RTE Treg/Tresp cells into ICOS + ? CD 31 ? or ICOS ? ? CD 31 ? memory Treg/Tresp cells and examined whether diverging pathways affected the suppressive activity of ICOS + and ICOS ? Treg cells in co‐culture with autologous Tresp cells. Compared with healthy controls, we found an increased differentiation of ICOS + RTE Treg/Tresp cells and ICOS ? RTE Treg cells through CD 31 + memory Treg/Tresp cells into CD 31 ? memory Treg/Tresp cells in ESRD and dialysis patients. In contrast, ICOS ? RTE Tresp cells showed an increased differentiation via ICOS ? mature naive ( MN ) Tresp cells into CD 31 ? memory Tresp cells. Thereby, the ratio of ICOS + Treg/ ICOS + Tresp cells was not changed, whereas that of ICOS ? Treg/ ICOS ? Tresp cells was significantly increased. This differentiation preserved the suppressive activity of both Treg populations in ESRD and partly in dialysis patients. After transplantation, the increased differentiation of ICOS + and ICOS ? RTE Tresp cells proceeded, whereas that of ICOS + RTE Treg cells ceased and that of ICOS ? RTE Treg cells switched to an increased differentiation via ICOS ? MN Treg cells. Consequently, the ratios of ICOS + Treg/ ICOS + Tresp cells and of ICOS ? Treg/ ICOS ? Tresp cells decreased significantly, reducing the suppressive activity of Treg cells markedly. Our data reveal that an increased tolerance‐inducing differentiation of ICOS + and ICOS ? Treg cells preserves the functional activity of Treg cells in ESRD patients, but this cannot be maintained during long‐term renal replacement therapy.