Ex vivo-expanded natural CD4+CD25+ regulatory T cells synergize with host T-cell depletion to promote long-term survival of allografts

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
Guliang XiaJoseph R Leventhal

Abstract

Foxp3(+)CD4(+)CD25(+) natural regulatory T (nT(reg)) cells have been shown in immunodeficient mice to suppress allograft rejection after adoptive cotransfer. We hypothesized that immunotherapy using ex vivo-expanded nT(reg) could suppress allograft rejection in wild-type mice. Donor alloantigen (alloAg) specificity of naive splenic nT(reg) was enriched in vitro by culturing with anti-CD3/CD28-coated Dynabeads plus bone marrow-derived dendritic cells (BM-DC) in the presence of interleukin (IL)-2 or IL-2 plus transforming growth factor (TGF)-beta. On average, 96.2% fresh CD4(+)CD25(+) nT(reg) were intracellular Foxp3(+). By d+20 in culture, 6.4% nT(reg) were Foxp3(+) following expansion with IL-2 alone, and 14.4% or 19.7% nT(reg) were Foxp3(+) when expanded with IL-2 plus 0.5 or 2.5 ng/mL TGF-beta, respectively. In vitro, alloAg-enriched, TGF-beta/IL-2-conditioned nT(reg) exerted stronger donor alloAg-specific suppression than cells with IL-2 alone in mixed lymphocyte reaction (MLR) assays. In vivo, alloAg-enriched, TGF-beta/IL-2-conditioned nT(reg) expressed high-level Foxp3 following infusion, effectively overcame acute rejection and induced long-term survival of donor but not third-party heart allografts in peritransplant host...Continue Reading

References

May 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Luis GracaHerman Waldmann
Feb 4, 2003·Nature Reviews. Immunology·Robert I LechlerLaurence A Turka
May 23, 2003·Journal of the American Society of Nephrology : JASN·Alan D SalamaMohamed H Sayegh
Jan 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mahzuz KarimKathryn J Wood
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Yufeng PengRichard A Flavell
Apr 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuki HayashiKoji Yasutomo
Jul 14, 2004·International Immunology·Christoph SchrammManfred Blessing
Sep 3, 2004·Nature Reviews. Immunology·Thomas R Malek, Allison L Bayer
Oct 7, 2004·International Immunology·Haruhiko YagiShimon Sakaguchi
Oct 27, 2004·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Guliang XiaBryon D Johnson
Nov 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Samuel HuberManfred Blessing
Mar 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Soren SchenkRobert L Fairchild
Apr 6, 2005·The Journal of Experimental Medicine·Julien C MarieAlexander Y Rudensky
Apr 23, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Isabelle SuffiaYasmine Belkaid
May 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jordi C OchandoJonathan S Bromberg
Sep 9, 2005·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Zoltán Fehérvari, Shimon Sakaguchi
Nov 15, 2005·European Journal of Immunology·Deborah J KasprowiczSteven F Ziegler
Dec 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alberto Sánchez-FueyoMohamed H Sayegh
Feb 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rita FucsAlberto Nobrega
Mar 21, 2006·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Guliang XiaBryon D Johnson
Mar 23, 2006·Annual Review of Immunology·Steven F Ziegler
May 26, 2006·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Xiaofeng JiangKen-ichiro Seino
Dec 22, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura StraussAlfred Zippelius
Feb 3, 2007·Nature Immunology·Wen LinTalal A Chatila
Feb 15, 2007·PLoS Biology·Stefan FloessJochen Huehn
Mar 24, 2007·Nature Reviews. Immunology·Daniel J Campbell, Steven F Ziegler
Apr 19, 2007·Nature Immunology·Ye Zheng, Alexander Y Rudensky
May 4, 2007·Journal of Leukocyte Biology·M Pyzik, C A Piccirillo
May 26, 2007·Nature Reviews. Immunology·Yuri P Rubtsov, Alexander Y Rudensky
Jun 27, 2007·The Journal of Experimental Medicine·Hyoung-Pyo Kim, Warren J Leonard
Jul 5, 2007·Science's STKE : Signal Transduction Knowledge Environment·Jared E LopesSteven F Ziegler

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Citations

Sep 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Xunrong LuoStephen D Miller
Dec 16, 2011·Journal of Molecular Cell Biology·Qizhi TangSang-Mo Kang
Nov 10, 2009·Transplantation·Elaine Long, Kathryn J Wood
Jul 26, 2011·Clinical & Developmental Immunology·Brett PhillipsNick Giannoukakis
Jul 20, 2010·Immunotherapy·Jorieke H PetersIrma Joosten
Aug 2, 2013·Experimental and Clinical Transplantation : Official Journal of the Middle East Society for Organ Transplantation·Hassan NikoueinejadBehzad Einollahi
Apr 11, 2013·Clinical & Developmental Immunology·Quan LiuXin Xiao Zheng
Nov 15, 2012·Immunotherapy·Nick Giannoukakis, Massimo Trucco
Oct 16, 2012·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Brad StoneJane H Buckner
Jan 14, 2009·Translational Research : the Journal of Laboratory and Clinical Medicine·Guliang XiaXunrong Luo
Jun 12, 2010·The Journal of Surgical Research·Lichen TengChangxi Wang
May 23, 2009·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·D IwamiM Niimi
Aug 7, 2009·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·T NozakiR L Fairchild
Jun 12, 2012·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·N M LerretX Luo
Jul 16, 2010·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·K L PothovenX Luo
Sep 18, 2015·Frontiers in Immunology·Niloufar SafiniaGiovanna Lombardi
Dec 17, 2009·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Youn-Hee ParkDong-Gyun Lim
Dec 25, 2015·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·M B EzzelarabA W Thomson
Sep 30, 2016·World Journal of Transplantation·Periklis DousdampanisAthanasia Mouzaki
Oct 26, 2010·Nature Reviews. Immunology·Angus W Thomson, Percy A Knolle
May 4, 2017·Journal of the American Society of Nephrology : JASN·Nicholas A Zwang, Joseph R Leventhal
Aug 22, 2009·Clinical Journal of the American Society of Nephrology : CJASN·Sacha A De SerresNader Najafian
Dec 8, 2019·Nature Reviews. Immunology·Caroline RaffinJeffrey A Bluestone
Jan 26, 2020·Gut·Jennie N CloughPeter M Irving
May 19, 2010·Expert Review of Clinical Immunology·Brett PhillipsMassimo Trucco
Dec 30, 2014·Physiological Reviews·Yanxia GuoRandolph J Noelle
Jun 20, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Alexandra JosephMelanie Ruzek
Sep 25, 2018·Transplantation·Chunyi ShaoReza Dana

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