Development of thymus autografts under the kidney capsule in the pig: A new “organ” for xenotransplantation

Lambrigts, Denis; Franssen, Colette; Martens, Henri; Calster, Pascale Van; Meurisse, Michel; Geenen, Vincent; Charlet-Renard, Chantal; Dewaele, A.; Coignoul, Freddy; Lamy, Marc; Alexandre, Guy P.

doi:10.1111/j.1399-3089.1996.tb00151.x

Cited by 20 publications

(8 citation statements)

References 14 publications

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“…In view of the importance of correction of thymus dysregulation in patients who are immunologically compromised, many groups have explored implanting thymic tissue into different sites in man and other animals (Kendall et al 1988;Martin-Fontecha et al 1993;Hosaka et al 1996;Lambrights et al 1996;Davis et al 1997;Markert et al 1997). In general, if the implants take well, thymic tissue is regenerated.…”

Section: Introductionmentioning

confidence: 99%

Immuno-characterisation of neuroendocrine cells of the rat thymus gland in vitro and in vivo

Botham

Jones

Kendall

2001

Cell and Tissue Research

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Primary cell cultures and organ fragments of rat thymus were characterised by use of a panel of antibodies raised against the neural adhesion molecule L1, tyrosine hydroxylase, protein gene product 9.5, nerve growth factor, calcitonin gene-related peptide, glial fibrillary acidic protein, vimentin, pan-cytokeratin, a ganglioside of neural crest and neuroendocrine cells (A2B5), and thymulin (4 beta). Immunoreactivity for neural markers only was identified in a single morphology (nerve-like) of cell in culture and throughout the adult thymus as fine, tortuous staining. Immunoreactivity for endocrine markers only was identified in polygonal epithelial-like cells in culture, throughout viable tissue in fragment culture and in the subcapsular cortex of the adult thymus. Immunoreactivity for both endocrine and neural markers was identified in three distinct morphologies in cell culture: elongate, spherical, and stellate. Similar results were observed in the mitotic periphery of the cultured fragments and in the medulla and cortico-medullary junction of the adult thymus. Cells with immunoreactivity to A2B5 were present in primary and fragment cultures and occurred throughout the adult thymus. The apparent diversity of cell immunoreactivity in primary and fragment thymic cultures suggests that numerous neural and endocrine factors may be required for the development and/or regeneration of the thymic microenvironment.

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Section: Introductionmentioning

confidence: 99%

Immuno-characterisation of neuroendocrine cells of the rat thymus gland in vitro and in vivo

Botham

Jones

Kendall

2001

Cell and Tissue Research

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“…Allogeneic thymic grafts were transplanted either as a composite "thymokidney" allograft or as separate thymic and kidney grafts from the same donor. To transplant donor thymus as a composite thymokidney graft, we used a method described recently for creating a vascularized thymic graft by implanting autologous thymic tissue under the renal capsule (9,45). Such thymokidneys were able to reconstitute T cells and restore immunocompetency (45).…”

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confidence: 99%

Thymic Transplantation in Miniature Swine. II. Induction of Tolerance by Transplantation of Composite Thymokidneys to Thymectomized Recipients

Yamada¹,

Shimizu

Utsugi³

et al. 2000

The Journal of Immunology

109

110

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Previous studies in our laboratory have demonstrated that the presence of the thymus is essential for rapid and stable tolerance induction in allotransplant models. We now report an attempt to induce tolerance to kidney allografts by transplanting donor thymic grafts simultaneously with the kidney in thymectomized recipients. Recipients were thymectomized 3 wk before receiving an organ and/or tissues from a class I-mismatched donor. Recipients received 1) a kidney allograft alone, 2) a composite allogeneic thymokidney (kidney with vascularized autologous thymic tissue under its capsule), or 3) separate kidney and thymic grafts from the same donor. All recipients received a 12-day course of cyclosporine. Thymectomized animals receiving a kidney allograft alone or receiving separate thymic and kidney grafts had unstable renal function due to severe rejection with the persistence of anti-donor cytotoxic T cell reactivity. In contrast, recipients of composite thymokidney grafts had stable renal function with no evidence of rejection histologically and donor-specific unresponsiveness. By postoperative day 14, the thymic tissue in the thymokidney contained recipient-type dendritic cells. By postoperative day 60, recipient-type class I positive thymocytes appeared in the thymic medulla, indicating thymopoiesis. T cells were both recipient and donor MHC-restricted. These data demonstrate that the presence of vascularized-donor thymic tissue induces rapid and stable tolerance to class I-disparate kidney allografts in thymectomized recipients. To our knowledge, this is the first evidence of functional vascularized thymic grafts permitting transplantation tolerance to be induced in a large animal model.

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“…56 In our institution, we have initiated a research program in xenotransplantation and we try to induce tolerance in baboons of grafted pig kidney following autotransplantation of pig thymus under kidney capsule (pig “thymo‐kidney”). 57…”

Section: Pharmacological Perspectives and Conclusion: Toward Tolerogmentioning

confidence: 99%

Cellular and Molecular Aspects of Thymic T‐Cell Education in Neuroendocrine Self Principles: Implications for Autoimmunity^a

Geenen

Martens

Vandersmissen

et al. 1998

Annals of the New York Academy of Sciences

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Thymic epithelial and nurse cells from different species express a repertoire of neuroendocrine polypeptide precursors. This repertoire exerts a dual role in T-lymphocyte selection according to their status either as cryptocrine signals or as neuroendocrine self-antigens of the peptide sequences that are processed from those precursors then presented to pre-T cells. Thymic neuroendocrine self-antigens correspond to peptide sequences highly conserved throughout evolution of their family. Though thymic MHC class I molecules are involved in the processing of thymic neuroendocrine self-antigens, preliminary data show that their presentation to pre-T cells is not allelically restricted. Thymic T-cell education in neuroendocrine families also implies that the structure of a given family may be presented to pre-T cells. Our studies have evidenced the homology between thymic neuroendocrine-related self-antigens and dominant T-cell epitopes of peripheral neuroendocrine signals (neuroendocrine autoantigens). The biochemical difference between neuroendocrine autoantigens and homologous thymic self-antigens might explain the opposite immune responses evoked by those two types of antigens (activation and memory induction vs. tolerogenic effect). Altogether, these studies support the therapeutic use of thymic neuroendocrine self-antigens in reprogramming the immunological self-tolerance that is broken in autoimmune endocrine diseases like insulin-dependent diabetes type I. As recently stated by P. M. Allen in an important review, the fate of developing T lymphocytes in the thymus is influenced by the numerous types of peptidic interactions within the thymic cellular environment. To define the precise nature of thymic cells and naturally occurring biochemical peptide signals involved in positive and negative selection of immature T cells has become a prominent objective for the future research efforts in thymic physiology. This paper will try to show how thymic neuroendocrine-related peptides synthesized and processed within the thymic microenvironment indeed can play a role both in the development of the peripheral T-cell repertoire and in the death of randomly rearranged, self-reactive T cells.

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Development of thymus autografts under the kidney capsule in the pig: A new “organ” for xenotransplantation

Cited by 20 publications

References 14 publications

Immuno-characterisation of neuroendocrine cells of the rat thymus gland in vitro and in vivo

Immuno-characterisation of neuroendocrine cells of the rat thymus gland in vitro and in vivo

Thymic Transplantation in Miniature Swine. II. Induction of Tolerance by Transplantation of Composite Thymokidneys to Thymectomized Recipients

Cellular and Molecular Aspects of Thymic T‐Cell Education in Neuroendocrine Self Principles: Implications for Autoimmunity^a

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Development of thymus autografts under the kidney capsule in the pig: A new “organ” for xenotransplantation

Cited by 20 publications

References 14 publications

Immuno-characterisation of neuroendocrine cells of the rat thymus gland in vitro and in vivo

Immuno-characterisation of neuroendocrine cells of the rat thymus gland in vitro and in vivo

Thymic Transplantation in Miniature Swine. II. Induction of Tolerance by Transplantation of Composite Thymokidneys to Thymectomized Recipients

Cellular and Molecular Aspects of Thymic T‐Cell Education in Neuroendocrine Self Principles: Implications for Autoimmunitya

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Cellular and Molecular Aspects of Thymic T‐Cell Education in Neuroendocrine Self Principles: Implications for Autoimmunity^a