Advances in the Use of Regulatory T-Cells for the Prevention and Therapy of Graft-vs.-Host Disease

被引:22
作者
Ramlal, Reshma [1 ]
Hildebrandt, Gerhard C. [1 ]
机构
[1] Univ Kentucky, Div Hematol & Bone Marrow Transplantat, Markey Canc Ctr, 800 Rose St, Lexington, KY 40536 USA
关键词
Tregs; graft versus host disease (GvHD); adoptive cellular therapy; CD4+CD25+FoxP3+T cells; BONE-MARROW-TRANSPLANTATION; VERSUS-LEUKEMIA; GVHD; BLOOD; INTERLEUKIN-2; INHIBITION; EXPANSION; RESPONSES; INFUSION;
D O I
10.3390/biomedicines5020023
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Regulatory T (Tregs) cells play a crucial role in immunoregulation and promotion of immunological tolerance. Adoptive transfer of these cells has therefore been of interest in the field of bone marrow and solid organ transplantation, autoimmune diseases and allergy medicine. In bone marrow transplantation, Tregs play a pivotal role in the prevention of graft-verus-host disease (GvHD). This has generated interest in using adoptive Treg cellular therapy in the prevention and treatment of GvHD. There have been several barriers to the feasibility of Treg cellular therapy in the setting of hematopoietic stem cell transplantation (HSCT) which include low Treg concentration in peripheral blood, requiring expansion of the Treg population; instability of the expanded product with loss of FoxP3 expression; and issues related to the purity of the expanded product. Despite these challenges, investigators have been able to successfully expand these cells both in vivo and in vitro and have demonstrated that they can be safely infused in humans for the prevention and treatment of GvHD with no increase in relapse risk or infections risk.
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页数:7
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共 34 条
  • [1] Proceedings from the Second Haploidentical Stem Cell Transplantation-Symposium Haplo2014, San Francisco, California, December 4, 2014
    Al Malki, Monzr M.
    Horowitz, Mary
    Handgretinger, Rupert
    Leung, Wing
    Roy, Denis-Claude
    Huang, Xiao-Jun
    Fuchs, Ephraim
    Locatelli, France
    Blaise, Didier
    Mineishi, Shin
    Martelli, Massimo
    Miller, Jeffrey
    June, Carl
    Ai, Hui-sheng
    Luznik, Leo
    Mavilio, Domenico
    Lugli, Enrico
    van den Brink, Marcel R. M.
    Champlin, Richard E.
    Ciurea, Stefan O.
    [J]. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2016, 22 (04) : 594 - 604
  • [2] [Anonymous], BLOOD
  • [3] ANTIN JH, 1992, BLOOD, V80, P2964
  • [4] CD4+CD25high regulatory cells in human peripheral blood
    Baecher-Allan, C
    Brown, JA
    Freeman, GJ
    Hafler, DA
    [J]. JOURNAL OF IMMUNOLOGY, 2001, 167 (03) : 1245 - 1253
  • [5] The role of regulatory T cells in the biology of greaft versus host disease
    Beres, Amy J.
    Drobyski, William R.
    [J]. FRONTIERS IN IMMUNOLOGY, 2013, 4
  • [6] Umbilical cord blood-derived T regulatory cells to prevent GVHD: kinetics, toxicity profile, and clinical effect
    Brunstein, Claudio G.
    Miller, Jeffrey S.
    McKenna, David H.
    Hippen, Keli L.
    Defor, Todd E.
    Sumstad, Darin
    Curtsinger, Julie
    Verneris, Michael R.
    MacMillan, Margaret L.
    Levine, Bruce L.
    Riley, James L.
    June, Carl H.
    Le, Chap
    Weisdorf, Daniel J.
    McGlave, Philip B.
    Blazar, Bruce R.
    Wagner, John E.
    [J]. BLOOD, 2016, 127 (08) : 1044 - 1051
  • [7] Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics
    Brunstein, Claudio G.
    Miller, Jeffrey S.
    Cao, Qing
    McKenna, David H.
    Hippen, Keli L.
    Curtsinger, Julie
    DeFor, Todd
    Levine, Bruce L.
    June, Carl H.
    Rubinstein, Pablo
    McGlave, Philip B.
    Blazar, Bruce R.
    Wagner, John E.
    [J]. BLOOD, 2011, 117 (03) : 1061 - 1070
  • [8] Blockade of interleukin-6 signaling augments regulatory T-cell reconstitution and attenuates the severity of graft-versus-host disease
    Chen, Xiao
    Das, Rupali
    Komorowski, Richard
    Beres, Amy
    Hessner, Martin J.
    Mihara, Masahiko
    Drobyski, William R.
    [J]. BLOOD, 2009, 114 (04) : 891 - 900
  • [9] Increased Foxp3+Helios+ Regulatory T Cells and Decreased Acute Graft-versus-Host Disease after Allogeneic Bone Marrow Transplantation in Patients Receiving Sirolimus and RGI-2001, an Activator of Invariant Natural Killer T Cells
    Chen, Yi-Bin
    Efebera, Yvonne A.
    Johnston, Laura
    Ball, Edward D.
    Avigan, David
    Lekakis, Lazaros J.
    Bachier, Carlos R.
    Martin, Paul
    Duramad, Omar
    Ishii, Yasuyuki
    Han, Semi
    Jung, Yu-Jin
    Lee, Dana
    Kunkel, Lori
    Negrin, Robert S.
    Bui, Jack D.
    [J]. BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2017, 23 (04) : 625 - 634
  • [10] Current and emerging strategies for the prevention of graft-versus-host disease
    Choi, Sung Won
    Reddy, Pavan
    [J]. NATURE REVIEWS CLINICAL ONCOLOGY, 2014, 11 (09) : 536 - 547