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A de Vries-van der Zwan

Publications and source records attributed to A de Vries-van der Zwan.

8 recordsLinked to original sources
PubMed1998

An alternative conditioning regimen for induction of specific skin graft tolerance across full major histocompatibility complex barriers.

Previously, we developed a well-tolerated single-day protocol for induction of stable multilineage chimerism and permanent donor-specific tolerance across major histocompatibility complex (MHC) barriers, with preservation of the host's normal immune responses. In our murine model, recipient mice were treated with a single dose of anti-CD3, anti-CD4, low dose total body irradiation (TBI; 3-6 Gy) and allogeneic bone marrow cells. An alternative cytoreductive strategy that is well-recognized in bone marrow transplantation, but has not been evaluated extensively in organ allograft recipients, involves the use of a combined chemotherapeutic drug treatment. The present data show that conditioning with low dose TBI, in a MHC-disparate donor-recipient combination, can be successfully substituted by a combined single low-dose dimethyl myleran (DMM)/cyclophosphamide (CY) therapy, resulting in both stable, mixed chimerism and specific skin graft tolerance.

Animals↗
PubMed1998

Haematopoietic stem cells can induce specific skin graft acceptance across full MHC barriers.

Previously, we and others have demonstrated in several animal models that the establishment of stable haematopoietic chimerism through allogeneic bone marrow transfusion provides an effective means for the development of specific transplantation tolerance. However, a major limitation to the clinical application of allogeneic bone marrow transfusion in immunosuppressed recipients for induction of tolerance to solid grafts, is the risk of graft-versus-host disease (GVHD). Therefore, it is important to identify the cell population needed for the induction of mixed chimerism and tolerance. Haematopoietic stem cells have the capacity of self-renewal and multilineage differentiation, and have been shown to reduce the risk of GVHD. We studied transfusion of two rich sources of stem cells, namely allogeneic fetal liver cells and a subset of purified bone marrow-derived progenitor cells (c-kit+) into anti-T cell monoclonal antibody-treated, low-dose irradiated recipient mice. Our data revealed that stable multilineage mixed chimerism and permanent donor-specific tolerance for skin, even when transplanted directly following conditioning, can be successfully achieved in this way, with no signs of GVHD.

Animals↗
PubMed1998

Specific tolerance induction and organ transplantation.

Induction of tolerance to histocompatibility antigens of an organ donor would eliminate the need for long-term administration of nonspecific immunosuppressive drugs associated with an increased risk of infection and malignancies. Recently, we established a murine model in which recipient mice were treated with a single dose of anti-CD3, anti-CD4, low dose of total body irradiation (TBI) and allogeneic bone marrow cells. Our results clearly demonstrate that stable multilineage mixed chimerism, immunocompetence and permanent donor-specific skin graft tolerance across full major histocompatibility (MHC) barriers can be successfully achieved in this way. The observations that the preparative regimen and skin transplantation can be performed on the same day, and that a significant reduction in irradiation dose is sufficient in haploidentical donor-recipient combinations (MHC-sharing effect), bring our protocol closer to clinical use.

Animals↗
PubMed1997

Specific tolerance induction and transplantation: a single-day protocol.

Bone marrow transfusion is a well-established method for induction of mixed hematopoietic chimerism and donor-specific tolerance in animal models. This procedure, however, is inapplicable in clinical transplantation using cadaveric donors due to the interval (1 week to 7 months) between tolerance induction and organ transplantation. For clinical use, it is essential that allografts be placed at the time of bone marrow transfusion. In the present study, we performed skin transplantation within 1 hour after a nonlethal conditioning regimen. Recipient mice were treated with anti-CD3, anti-CD4, low-dose total body irradiation (3 to 6 Gy TBI) and fully mismatched or haploidentical donor bone marrow cells. Stable multilineage chimerism and specific T-cell nonresponsiveness developed. Donor skin grafts were permanently accepted. These results suggest that this single day protocol has clear potential for application in both cadaveric and living-related organ transplantation.

Animals↗
PubMed1996

A substantial level of mixed chimerism is required for the induction of permanent transplantation tolerance.

The induction of donor-specific transplantation tolerance is a major goal in organ transplantation, in order to eliminate the requirement for lifelong immunosuppressive therapy. Previously, we have developed a murine bone marrow transplantation model in which recipient mice were treated with a single dose of anti-CD3 and low dose whole body irradiation (WBI). Transfusion of donor bone marrow cells across a full H-2 disparity resulted in induction of high levels of stable mixed chimerism, specific T cell non-responsiveness and indefinite skin allograft survival. The present study has focused on manipulation of the level of chimerism in this model by varying the number of infused bone marrow cells, varying the dose of WBI and addition of syngeneic bone marrow cells. Our results indicate that a substantial level of chimerism is needed for induction of transplantation tolerance. In addition, in the semi-allogeneic donor-recipient combination an even lower dose of WBI was sufficient of engraftment of bone marrow cells and subsequent tolerance induction. We suggest that sharing of MHC antigens between donor and recipient might play an important role in facilitating the development of chimerism and tolerance in organ transplantation.

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