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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Shimizu, Ichiro Fudaba, Yasuhiro Shimizu, Akira Yang, Yong-Guang Sykes, Megan
Description	Country affiliation: United States Author Affiliation: Shimizu I ( Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.)
Abstract	BACKGROUND: 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. METHODS: 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. RESULTS: 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 grafts functioned. In animals with surviving SW grafts, thymocytes from the SW but not the HU grafts showed specific unresponsiveness to the SW donor. CONCLUSION: Swine thymus grafts support generation of human T cells with a diverse T cell receptor repertoire. Human thymocytes in human thymus grafts are not tolerized by the presence of an additional porcine thymus, but tolerance might be achieved by postthymic encounter with porcine antigens.
File Format	HTM / HTML
ISSN	00411337
e-ISSN	15346080
DOI	10.1097/TP.0b013e318182d47a
Journal	Transplantation Journal
Issue Number	4
Volume Number	86
Language	English
Publisher	Lippincott Williams & Wilkins
Publisher Date	2008-08-27
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Transplantation T-lymphocytes Immunology Thymus Gland Transplantation Transplantation, Heterologous Animals Cd4-positive T-lymphocytes Cd8-positive T-lymphocytes Fetus Immune Tolerance Lymphocyte Culture Test, Mixed Major Histocompatibility Complex Mice Mice, Inbred Nod Mice, Scid Receptors, Antigen, T-cell Genetics Subrenal Capsule Assay Swine Swine, Miniature Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Transplantation

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