PMID- 19459808 OWN - NLM STAT- MEDLINE DCOM- 20091202 LR - 20230124 IS - 1600-6143 (Electronic) IS - 1600-6135 (Print) IS - 1600-6135 (Linking) VI - 9 IP - 6 DP - 2009 Jun TI - Induction of human T-cell tolerance to pig xenoantigens via thymus transplantation in mice with an established human immune system. PG - 1324-9 LID - 10.1111/j.1600-6143.2009.02646.x [doi] AB - Thymus xenotransplantation has been shown to induce tolerance to porcine xenografts in mice and to permit survival of alpha1,3Gal-transferase knockout porcine kidney xenografts for months in nonhuman primates. We evaluated the ability of porcine thymus xenotransplantation to induce human T-cell tolerance using a humanized mouse (hu-mouse) model, where a human immune system is preestablished by implantation of fetal human thymus tissue under the kidney capsule and intravenous injection of CD34(+) hematopoietic stem/progenitor cells. Human T-cell depletion with an anti-CD2 mAb following surgical removal of human thymic grafts prevented the initial rejection of porcine thymic xenografts in hu-mice. In these hu-mice, porcine thymic grafts were capable of supporting human thymopoiesis and T-cell development, and inducing human T-cell tolerance to porcine xenoantigens. Human T cells from these mice responded strongly to third-party pig, but not to the thymic donor swine leukocyte antigen (SLA)-matched pig stimulators in a mixed lymphocyte reaction (MLR) assay. Anti-pig xenoreactive antibodies declined in these hu-mice, whereas antibody levels increased in nontolerant animals that rejected porcine thymus grafts. These data show that porcine thymic xenotransplantation can induce donor-specific tolerance in immunocompetent hu-mice, supporting this approach for tolerance induction in clinical xenotransplantation. FAU - Habiro, K AU - Habiro K AD - Transplantation Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. FAU - Sykes, M AU - Sykes M FAU - Yang, Y-G AU - Yang YG LA - eng GR - P01 AI045897/AI/NIAID NIH HHS/United States GR - R01 AI064569/AI/NIAID NIH HHS/United States GR - R01 AI064569-02/AI/NIAID NIH HHS/United States GR - P01 AI 045897/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20090520 PL - United States TA - Am J Transplant JT - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JID - 100968638 RN - 0 (Antibodies, Monoclonal) RN - 0 (CD2 Antigens) SB - IM MH - Animals MH - Antibodies, Monoclonal MH - CD2 Antigens/immunology MH - Humans MH - Immune Tolerance/immunology MH - Mice MH - Mice, SCID MH - Swine MH - Swine, Miniature MH - T-Lymphocytes/immunology/transplantation MH - Thymus Gland/*transplantation MH - Transplantation, Heterologous/*immunology PMC - PMC2752337 MID - NIHMS135433 EDAT- 2009/05/23 09:00 MHDA- 2009/12/16 06:00 PMCR- 2010/06/01 CRDT- 2009/05/23 09:00 PHST- 2009/05/23 09:00 [entrez] PHST- 2009/05/23 09:00 [pubmed] PHST- 2009/12/16 06:00 [medline] PHST- 2010/06/01 00:00 [pmc-release] AID - S1600-6135(22)01722-1 [pii] AID - 10.1111/j.1600-6143.2009.02646.x [doi] PST - ppublish SO - Am J Transplant. 2009 Jun;9(6):1324-9. doi: 10.1111/j.1600-6143.2009.02646.x. Epub 2009 May 20.