Evidence That Functional Deletion of Donor-Reactive T Lymphocytes in Kidney Allograft Recipients Can Occur at the Level of Cytotoxic T Cells, Il-2-Producing T Cells, or Both

Zanker, B; Jooss-Rüdiger, J; He, Franz; Wagner, Heinz‐Theo; Kabelitz, Dieter

doi:10.1097/00007890-199309000-00025

Cited by 24 publications

(4 citation statements)

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“…Our data on donor-specific hyporeactive CTLp confirm earlier results obtained in patients with well-functioning kidney or heart allografts [16,35]. Additionally, Zanker et al [24] described 19 kidney transplant recipients of whom only a few developed reduced T-cell reactivity; three patients developed reduced HTLpf, one patient reduced CTLpf, and two patients reduced HTLpf and CTLpf. De Haan et al [23,36] found a decrease in donor-specific CTLp 1-2 years after liver and lung transplantation compared with before transplantation, but this decrease did not correlate with decreased HTLp.…”

Section: Discussionsupporting

confidence: 90%

“…Some studies have described T-cell reactivity before (no immunosuppression) and after transplantation (high dose immunosuppression) [16,[21][22][23][24]. To date, only a few studies have measured T-cell reactivity before (high dose immunosuppression) and after tapering (low dose immunosuppression) immunosuppression, although in a small number of patients [17,20,25,26].…”

Section: Introductionmentioning

confidence: 99%

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Down-regulated donor-specific T-cell reactivity during successful tapering of immunosuppression after kidney transplantation

Besouw¹,

Mast²,

Kuiper³

et al. 2002

Clinical and Experimental Immunology

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SUMMARY Stable cadaveric renal transplant patients were routinely converted from cyclosporin A (CsA) to either azathioprine (AZA) or mycophenolate mofetil (MMF) 1 year after transplantation to reduce the side effects of long-term immunosuppressive therapy. Thereafter, the AZA and MMF dose was gradually tapered to 50% at 2 years after transplantation. We questioned whether a reduction of immunosuppressive treatment results in a rise of donor-specific T-cell reactivity. Before transplantation (no immunosuppression), 1 year (high dose immunosuppression) and 2 years (low dose immunosuppression) after transplantation, the T-cell reactivity of peripheral blood mononuclear cells (PBMC) against donor and third-party spleen cells was tested in mixed lymphocyte cultures (MLC) and against tetanus toxoid (TET) to test the general immune response. We also measured the frequency of donor and third-party reactive helper (HTLpf) and cytotoxic (CTLpf) T-lymphocyte precursors in a limiting dilution assay. Donor-specific responses, calculated by relative responses (RR = donor/third-party reactivity), were determined. Comparing responses after transplantation during high dose immunosuppression with responses before transplantation (no immmunosuppression), the donor-specific MLC-RR (P = 0·04), HTLp-RR (P = 0·04) and CTLp-RR (P = 0·09) decreased, while the TET-reactivity did not change. Comparing the responses during low dose with high dose immunosuppression, no donor- specific differences were found in the MLC-RR, HTLp-RR and CTLp-RR, although TET-reactivity increased considerably (P = 0·0005). We observed a reduction in donor-specific T-cell reactivity in stable patients after renal transplantation during in vivo high dose immunosuppression. Tapering of the immunosuppressive load had no rebound effect on the donor-specific reactivity, while it allowed recovery of the response to nominal antigens.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Down-regulated donor-specific T-cell reactivity during successful tapering of immunosuppression after kidney transplantation

Besouw¹,

Mast²,

Kuiper³

et al. 2002

Clinical and Experimental Immunology

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“…Thus in most cases close collaboration between clinical and experimental departments is necessary, and because such collaboration seems to be rare, only very few patients have been monitored by LDA. Evidence for a predictive value of CTLp frequencies after transplantation is provided mainly by two studies of one group (5,6 All T-cell frequencies were measured before transplantation and at least twice after transplantation. In contrast to our study, there was no strict time schedule for the investigation after transplantation.…”

Section: Discussionmentioning

confidence: 99%

Failure of in vitro T‐cell assays to predict clinical outcome after human kidney transplantation

Steinmann

Kaden

May

et al. 1994

Clinical Laboratory Analysis

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Allotransplant rejection is a T-cell-dependent reaction. Functional in vitro T-cell assays are being used widely for donor-recipient matching in bone marrow transplantation and have recently been used in some centres for transplant monitoring. In order to assess tolerance induction after clinical transplantation, we measured the T-cell response of the host against donor spleen cells of 33 kidney transplant patients before and every 3 months after transplantation over a period of 18 months. The T-cell reactivity before transplantation was not significantly different in any of the assays in rejecting and non-rejecting patients. In the classical mixed lymphocyte culture (MLC), a donor-specific loss of reactivity was seen only in a patient with a CMV-associated irreversible transplant rejection. One patient with chronic rejection acquired a very high MLC response against donor spleen cells and a high response against third-party cells. Little or nonspecific changes were seen in the MLCs of all other patients. Using the method of limiting dilution analysis (LDA), we found a significant reduction of donor-specific cytotoxic T-cell precursors (CTL-p) within the first 3 months after transplantation in most patients with high antidonor CTL-p frequencies before transplantation. The reduction of donor-specific CTL-p was seen in patients with rejection episodes as well as in patients without. Thus we conclude, in contrast to others, that MLC and CTL-p LDA have no predictive value on the outcome of clinical transplantation.

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“…Several studies have demonstrated that a reduction in circulating CTL is associated with stable engraftment [2,3,9]. Interestingly, our study suggests that in patients with stable engraftment who remained free from GVD, no consistent reduction in circulating pCTL numbers was observed over time.…”

Section: Discussionmentioning

confidence: 46%

Donor-specific CTL frequencies in peripheral blood in relation to graft vascular disease after clinical heart transplantation

Besouw¹,

Daane²,

Kuiper³

et al. 1998

Transplant Int

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Cellular mechanisms may play a role in the development of graft vascular disease (GVD). We previously demonstrated that G V D correlated with an increase of donor-specific T-helper 1 cytokine production by graft-infiltrating lymphocytes but not by peripheral blood mononuclear cells (PBMC). These T-helper 1 cytokines aid the generation of cytotoxic T-lymphocytes (CTL). In the present report, we investigated whether there is a relationship between the frequency of donor-specific CTL precursors (pCTL) in PBMC and the development of GVD. We tested PBMC samples of five patients with GVD and five patients without GVD in the periods 3-6 months, 1 year, and 3 years after heart transplantation. At all time points, GVD was not related to the number of pCTL. In conclusion, donor-specific cellular tests in peripheral blood could not be related to GVD. Apparently, donor-specific reactions associated with the induction of GVD can only be monitored in the graft.

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Evidence That Functional Deletion of Donor-Reactive T Lymphocytes in Kidney Allograft Recipients Can Occur at the Level of Cytotoxic T Cells, Il-2-Producing T Cells, or Both

Cited by 24 publications

References 0 publications

Down-regulated donor-specific T-cell reactivity during successful tapering of immunosuppression after kidney transplantation

Down-regulated donor-specific T-cell reactivity during successful tapering of immunosuppression after kidney transplantation

Failure of in vitro T‐cell assays to predict clinical outcome after human kidney transplantation

Donor-specific CTL frequencies in peripheral blood in relation to graft vascular disease after clinical heart transplantation

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