Comparison of human T cell repertoire generated in xenogeneic porcine and human thymus grafts.

Transplantation
Ichiro ShimizuMegan Sykes

Abstract

Xenogeneic thymus transplantation is an effective approach to achieving T cell tolerance across highly disparate xenogeneic species barriers. We have previously demonstrated that phenotypically normal, specifically tolerant human T cells are generated in porcine thymic grafts. In this study, we assessed the diversity of the human T cell repertoire generated in porcine thymic xenografts. We also examined the ability of porcine thymus grafts to coexist with human thymus grafts. Fetal swine (SW) or human (HU) thymus with human fetal liver fragments were transplanted under the kidney capsule of 3Gy irradiated NOD/SCID mouse recipients. Thymus tissue was harvested approximately 16 weeks posttransplant for analysis of mixed lymphocyte reactions and spectratyping of human CD4 and CD8 single positive thymocytes. T cell receptor beta genes of human CD4 and CD8 single positive cells developing in HU and SW thymus grafts showed similar, normal CDR3 length distributions. Human T cells developing in SW thymus grafts showed specific unresponsiveness to the major histocompatibility complex of the donor swine in mixed leukocyte reaction assays. In two of three animals receiving SW and HU thymus grafts under opposite kidney capsules, both graft...Continue Reading

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Citations

Nov 13, 2009·Leukemia Research·Mario VitacolonnaMargot Zöller
Dec 9, 2008·Transplant Immunology·David H SachsKazuhiko Yamada
Jan 13, 2009·Xenotransplantation·Mårten K J Schneider, Jörg D Seebach
Feb 13, 2014·Immunological Reviews·Adam GriesemerMegan Sykes
Oct 23, 2009·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·A D GriesemerK Yamada
Sep 25, 2017·Current Opinion in Organ Transplantation·Kazuhiko YamadaDavid H Sachs
Mar 29, 2019·The Journal of Clinical Investigation·Mohsen Khosravi-MaharlooeiMegan Sykes
Nov 5, 2019·Science Immunology·Megan Sykes, David H Sachs
Nov 1, 2018·Current Opinion in Organ Transplantation·Nathaly P LloreAdam Griesemer
Nov 20, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yasuhiro FudabaMegan Sykes
Mar 5, 2014·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hannes KalscheuerMegan Sykes
Oct 26, 2021·The Journal of Allergy and Clinical Immunology·Rafael Gras-PeñaMegan Sykes
Dec 14, 2021·Molecular Metabolism·Mohsen Khosravi-MaharlooeiRemi J Creusot

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