Transplantation Tolerance and Autoimmunity After Xenogeneic Thymus Transplantation1

  title={Transplantation Tolerance and Autoimmunity After Xenogeneic Thymus Transplantation1},
  author={Guliang Xia and Jozef Goebels and Omer Rutgeerts and Michel Vandeputte and Mark Waer},
  journal={The Journal of Immunology},
  pages={1843 - 1854}
Successful grafting of vascularized xenografts (Xgs) depends on the ability to reliably induce both T cell-independent and -dependent immune tolerance. After temporary NK cell depletion, B cell suppression, and pretransplant infusion of donor Ags, athymic rats simultaneously transplanted with hamster heart and thymus Xgs developed immunocompetent rat-derived T cells that tolerated the hamster Xgs but provoked multiple-organ autoimmunity. The autoimmune syndrome was probably due to an… 

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Pathogenesis of Autoimmunity After Xenogeneic Thymus Transplantation1

AIS after xenothymus transplantation in nude rats is due to a combination of insufficient intrathymic presence of host-type epithelial cell Ags and a defective generation of regulatory T lymphocytes.

Xenogeneic Thymus Transplantation Pathogenesis of Autoimmunity After

AIS after xenothymus transplantation in nude rats is due to a combination of insufficient presence of rat epithelial cell Ags and a defective generation of regulatory lymphocytes.

Partial Tolerance Induced by Transplantation of Spatially Separated Thymuses: A Cue for T Cell Retolerization in Thymus Grafts

The data suggest that the immune tolerance induced by mixed thymus transplants could be partially reversed if theThymus tissues from donors and recipients were segregated by spatial telorism.

Abnormal Regulatory and Effector T Cell Function Predispose to Autoimmunity following Xenogeneic Thymic Transplantation1

The authors' data implicate abnormalities in postthymic maturation, expansion, and/or survival of T cells positively selected by a xenogeneic MHC, as well as incomplete intrathymic deletion of thymocytes recognizing host tissue-specific Ags, in autoimmune pathogenesis.

Occurrence of autoimmunity after xenothymus transplantation in T-cell-deficient mice depends on the thymus transplant technique.

A novel vascular pouch technique of xenothymus transplantation that prevents the development of autoimmunity in nude mice is described and is suggested to be related to a superior development of regulatory T-cells.

Despite efficient intrathymic negative selection of host-reactive T cells, autoimmune disease may develop in porcine thymus-grafted athymic mice: evidence for failure of regulatory mechanisms suppressing autoimmunity1

A key role for mouse CD4+ T cells is demonstrated in causing autoimmune disease in this model and the importance of regulatory mechanisms in addition to intrathymic clonal deletion for the maintenance of tolerance to recipient antigens is suggested.

B cell tolerance and xenotransplantation

This review summarizes recent advances in the understanding of B cell tolerance in rodent models and patients and describes strategies for tolerance induction developed in the animal models that may be applied clinically as an understanding of their mechanisms emerges.

Induction and Maintenance of T-dependent or T-independent Xenotolerance by Nonprimarily-Vascularized Skin or Thymus Grafts

Skin grafts were as effective as vascularized heart grafts to induce/maintain T-independent xenotolerance and sensitize the T-cell compartment when transplanted concomitantly with thymus grafts.

CTLA-4 blockade in murine bone marrow chimeras induces a host-derived antileukemic effect without graft-versus-host disease

The findings reveal the potential of using CTLA-4 blockade to establish antileukemic effects after allogeneic hematopoietic stem cell transplantation, provided autoimmunity can be controlled.

Rapidly induced, T-cell independent xenoantibody production is mediated by marginal zone B cells and requires help from NK cells.

It is shown, using models involving T-cell-deficient athymic recipient mice, that rapidly induced, T- cell-independent xenoantibody production is mediated by marginal zone B lymphocytes and requires help from natural killer cells.



Induction of specific transplantation tolerance across xenogeneic barriers in the T-independent immune compartment

In vivo immunization and in vitro cy-totoxicity assays indicated that this species-specific tolerance was based on B-lymphocyte and NK-cell tolerance respectively.

Skin graft tolerance across a discordant xenogeneic barrier

The principle that tolerance, measured by the stringent criterion of skin grafting, can be induced across a widely disparate species barrier is demonstrated.

Reconstitution with syngeneic plus allogeneic or xenogeneic bone marrow leads to specific acceptance of allografts or xenografts

Reconstituting the irradiated host with T-cell depleted bone marrow containing both host (syngeneic) and donor (allogeneic or xenogeneic) components leads to long-term survival of the reconstituted animals and specific prolongation of subsequent skin grafts of donor type.

Specific tolerance across a discordant xenogeneic transplantation barrier.

  • L. A. LeeH. Gritsch M. Sykes
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1994
It is demonstrated here that xenogeneic swine thymic transplants can induce tolerance to swine antigens in mice, while positively selecting functional host CD4+ T cells, which confirmed that the new T cells were functional and were tolerant to pig antIGens.

Immune restoration by fetal pig thymus grafts in T cell-depleted, thymectomized mice.

Examination of the phenotype and function of murine T cells that develop in FP THY/LIV grafts in mice shows that xenogeneic thymic replacement might have a potential role in the reconstitution of immunity in patients afflicted with immunodeficiencies affecting the thymus.

Autoimmune diseases developed in athymic nude mice grafted with embryonic thymus of xenogeneic origin

The results together suggested that the microenvironment of grafted thymi, even if xenogeneic, is able to educate host T cell precursors, however, this reconstitution of functions does not always induce tolerance to certain autoantigens, resulting in development of multiple autoimmune lesions.

Specific tolerance induction across a xenogeneic barrier: production of mixed rat/mouse lymphohematopoietic chimeras using a nonlethal preparative regimen

The ability to induce donor-specific tolerance across xenogeneic barriers using a nonmyeloablative and nonlethal preparative regimen provides a valuable model for the study of mechanisms of Xenogeneic transplantation tolerance.

Mechanisms of transplantation tolerance.

While thymic deletion of T cells appears to be a mainstay of self-tolerance, its role in transplantation tolerance now seems to be less significant, and extrathymic mechanisms of transplantationolerance seem to be major factors in long-term graft acceptance.

Normal development in porcine thymus grafts and specific tolerance of human T cells to porcine donor MHC.

It is shown that porcine thymus grafts in immunodeficient mice support normal development of polyclonal, functional human T cells, suggesting the thymic transplantation approach to achieving tolerance with restoration of immunocompetence may be applicable to xenotransplantation of pig tissues to humans.


The focus of the present study was to explore the feasibility of autologous thymic transplantation to produce a new transplantable organ (thymokidney) and to examine the function of subsequent vascularized thymokidsney transplants in T cell development.