Inhibition of CD4+CD25+ regulatory T-cell function by calcineurin-dependent interleukin-2 production

Blood
Robert ZeiserRobert S Negrin

Abstract

CD4+CD25+ regulatory T (Treg) cells control immunologic tolerance and antitumor immune responses. Therefore, in vivo modification of Treg function by immunosuppressant drugs has broad implications for transplantation biology, autoimmunity, and vaccination strategies. In vivo bioluminescence imaging demonstrated reduced early proliferation of donor-derived luciferase-labeled conventional T cells in animals treated with Treg cells after major histocompatibility complex mismatch bone marrow transplantation. Combining Treg cells with cyclosporine A (CSA), but not rapamycin (RAPA) or mycophenolate mofetil (MMF), suppressed Treg function assessed by increased T-cell proliferation, graft-versus-host disease (GVHD) severity, and reduced survival. Expansion of Treg and FoxP3 expression within this population was lowest in conjunction with CSA, suggesting that calcineurin-dependent interleukin 2 (IL-2) production is critically required for Treg cells in vivo. The functional defect of Treg cells after CSA exposure could be reversed by exogenous IL-2. Further, the Treg plus RAPA combination preserved graft-versus-tumor (GVT) effector function against leukemia cells. Our data indicate that RAPA and MMF rather than CSA preserve function of T...Continue Reading

References

Jan 13, 1995·The Journal of Biological Chemistry·C J SabersR T Abraham
May 2, 1994·Journal of Immunological Methods·A B Lyons, C R Parish
Aug 18, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·A MehlingS Beissert
Feb 13, 2001·Current Opinion in Genetics & Development·R K Assoian, M A Schwartz
Aug 8, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·S GregoriL Adorini
Jul 3, 2002·Nature Reviews. Immunology·Ethan M Shevach
Aug 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Udaya K LiyanageDavid C Linehan
Sep 18, 2002·The Journal of Experimental Medicine·Gláucia C FurtadoJuan J Lafaille
Jan 11, 2003·Science·Shohei HoriShimon Sakaguchi
Mar 4, 2003·Nature Immunology·Jason D FontenotAlexander Y Rudensky
Apr 30, 2003·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Stephen C JonesRobert Korngold
May 8, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Francesca GranucciPaola Ricciardi-Castagnoli
Dec 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yu-An CaoChristopher H Contag
Feb 10, 2004·European Journal of Immunology·Angela M ThorntonEthan M Shevach
May 22, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Angela M ThorntonEthan M Shevach
Sep 3, 2004·Nature Reviews. Immunology·Thomas R Malek, Allison L Bayer
Mar 5, 2005·Blood·Manuela BattagliaMaria-Grazia Roncarolo
Jun 14, 2005·Breast Cancer Research and Treatment·Carsten T ViehlPeter S Goedegebuure
Oct 18, 2005·Nature Immunology·Jason D FontenotAlexander Y Rudensky
Jan 31, 2006·Nature Medicine·Manuel E EngelhornAlan N Houghton

❮ Previous
Next ❯

Citations

Nov 8, 2011·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Di JinYong Zhao
Jun 28, 2008·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Jeffery T FletcherStephen I Alexander
Mar 9, 2011·International Journal of Hematology·John E Levine
Jul 15, 2009·Bone Marrow Transplantation·J M PalmerN J Chao
Dec 1, 2009·Bone Marrow Transplantation·S PaczesnyP Reddy
Jun 26, 2012·Cellular & Molecular Immunology·Marina Cetkovic-CvrljeKetaki Ghate
Sep 17, 2008·Immunology and Cell Biology·Esma S YolcuShai Yarkoni
Oct 17, 2012·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jianyu WengXin Du
Aug 23, 2006·Nature Immunology·Lena Ho, Gerald Crabtree
Feb 17, 2009·Nature Medicine·Elmer B SantosRenier J Brentjens
Jul 27, 2007·Nature Reviews. Immunology·Maria-Grazia Roncarolo, Manuela Battaglia
Apr 25, 2009·Nature Reviews. Immunology·Angus W ThomsonGiorgio Raimondi
Dec 2, 2011·The New England Journal of Medicine·John KorethRobert J Soiffer
Sep 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Brian A RabinovichPatrick Hwu
Aug 28, 2013·The Journal of Experimental Medicine·Dragana JankovicRobert Zeiser
Jul 30, 2010·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Philippe GrimbertPhilippe Lang
Mar 1, 2012·Journal of Clinical Neuromuscular Disease·Nicholas ParzialeJayashri Srinivasan
Feb 10, 2009·Transplantation·Thijs K HendrikxCarla C Baan
Apr 28, 2009·Transplantation·Oriol BestardJosep M Grinyó
Jun 18, 2010·Transplantation·Adam D GriesemerMark A Hardy
Nov 30, 2006·Annual Review of Immunology·Lisbeth A WelniakWilliam J Murphy
Sep 29, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nancy M HardyMichael R Bishop
Jan 28, 2010·Blood·Natascha Hermann-Kleiter, Gottfried Baier

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