Review Article

Cell Therapy in Solid Organ Transplantation

Author(s): Songjie Cai and Anil Chandraker*

Volume 19, Issue 2, 2019

Page: [71 - 80] Pages: 10

DOI: 10.2174/1566523219666190603103840

Price: $65


Transplantation is the only cure for end-stage organ failure. Current immunosuppressive drugs have two major limitations: 1) non antigen specificity, which increases the risk of cancer and infection diseases, and 2) chronic toxicity. Cell therapy appears to be an innovative and promising strategy to minimize the use of immunosuppression in transplantation and to improve long-term graft survival. Preclinical studies have shown efficacy and safety of using various suppressor cells, such as regulatory T cells, regulatory B cells and tolerogenic dendritic cells. Recent clinical trials using cellbased therapies in solid organ transplantation also hold out the promise of improving efficacy. In this review, we will briefly go over the rejection process, current immunosuppressive drugs, and the potential therapeutic use of regulatory cells in transplantation.

Keywords: Cell therapy, immune suppression, solid organ transplant, chronic toxicity, antigen specificity, DAMP.

Graphical Abstract
Floerchinger B, Yuan X, Jurisch A, et al. Inflammatory immune responses in a reproducible mouse brain death model. Transpl Immunol 2012; 27(1): 25-9.
[] [PMID: 22549100]
Issa FG, Goto R, Wood KJ. Immunological principles of acute rejection. In: Kleinv AA, Lewis CJ, Madsen JC, Eds. Organ Transplantation: A Clinical Guide UK. Cambridge University Press 2011; pp. 9-18.
Sheen JH, Heeger PS. Effects of complement activation on allograft injury. Curr Opin Organ Transplant 2015; 20(4): 468-75.
[] [PMID: 26132735]
Hoffmann SC, Kampen RL, Amur S, et al. Molecular and immunohistochemical characterization of the onset and resolution of human renal allograft ischemia-reperfusion injury. Transplantation 2002; 74(7): 916-23.
[] [PMID: 12394831]
Li W, Nava RG, Bribriesco AC, et al. Intravital 2-photon imaging of leukocyte trafficking in beating heart. J Clin Invest 2012; 122(7): 2499-508.
[] [PMID: 22706307]
Pittman K, Kubes P. Damage-associated molecular patterns control neutrophil recruitment. J Innate Immun 2013; 5(4): 315-23.
[] [PMID: 23486162]
Zhuang Q, Lakkis FG. Dendritic cells and innate immunity in kidney transplantation. Kidney Int 2015; 87(4): 712-8.
[] [PMID: 25629552]
Lakkis FG. Where is the alloimmune response initiated? Am J Transplant 2003; 3(3): 241-2.
[] [PMID: 12614275]
Valujskikh A, Heeger PS. CD4+ T cells responsive through the indirect pathway can mediate skin graft rejection in the absence of interferon-gamma. Transplantation 2000; 69(5): 1016-9.
[] [PMID: 10755571]
Syrjälä SO, Keränen MA, Tuuminen R, et al. Increased Th17 rather than Th1 alloimmune response is associated with cardiac allograft vasculopathy after hypothermic preservation in the rat. J Heart Lung Transplant 2010; 29(9): 1047-57.
[] [PMID: 20591689]
Rovere-Querini P, Capobianco A, Scaffidi P, et al. HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep 2004; 5(8): 825-30.
[] [PMID: 15272298]
Schiller M, Heyder P, Ziegler S, et al. During apoptosis HMGB1 is translocated into apoptotic cell-derived membranous vesicles. Autoimmunity 2013; 46(5): 342-6.
[] [PMID: 23194089]
Dumitriu IE, Baruah P, Valentinis B, et al. Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products. J Immunol 2005; 174(12): 7506-15.
[] [PMID: 15944249]
Tsung A, Klune JR, Zhang X, et al. HMGB1 release induced by liver ischemia involves Toll-like receptor 4 dependent reactive oxygen species production and calcium-mediated signaling. J Exp Med 2007; 204(12): 2913-23.
[] [PMID: 17984303]
Wu MC, Gilmour TD, Mantovani S, Woodruff TM. The receptor for advanced glycation endproducts does not contribute to pathology in a mouse mesenteric ischemia/reperfusion-induced injury model. Front Immunol 2015; 6: 614.
[] [PMID: 26697010]
Shen H, Song Y, Colangelo CM, et al. Haptoglobin activates innate immunity to enhance acute transplant rejection in mice. J Clin Invest 2012; 122(1): 383-7.
[] [PMID: 22156194]
Huang Y, Yin H, Han J, et al. Extracellular hmgb1 functions as an innate immune-mediator implicated in murine cardiac allograft acute rejection. Am J Transplant 2007; 7(4): 799-808.
[] [PMID: 17331117]
Braza F, Brouard S, Chadban S, Goldstein DR. Role of TLRs and DAMPs in allograft inflammation and transplant outcomes. Nat Rev Nephrol 2016; 12(5): 281-90.
[] [PMID: 27026348]
Wood KJ, Mariat C, Thaunat O, Mousson C, Rifle G. Bridging innate with adaptive immunity in transplantation: Triggers, sensors, and modulators. Transplantation 2014; 98(10): 1021-4.
[] [PMID: 25286058]
Bernard A, Lamy And L, Alberti I. The two-signal model of T-cell activation after 30 years. Transplantation 2002; 73(1): S31-5.
[] [PMID: 11810059]
Greenfield EA, Nguyen KA, Kuchroo VK. CD28/B7 costimulation: A review. Crit Rev Immunol 1998; 18(5): 389-418.
[] [PMID: 9784967]
Grewal IS, Flavell RA. The role of CD40 ligand in costimulation and T-cell activation. Immunol Rev 1996; 153: 85-106.
[] [PMID: 9010720]
Usui Y, Akiba H, Takeuchi M, et al. The role of the ICOS/B7RP-1 T cell costimulatory pathway in murine experimental autoimmune uveoretinitis. Eur J Immunol 2006; 36(11): 3071-81.
[] [PMID: 17039566]
Yang J, Riella LV, Chock S, et al. The novel costimulatory programmed death ligand 1/B7.1 pathway is functional in inhibiting alloimmune responses in vivo. J Immunol 2011; 187(3): 1113-9.
[] [PMID: 21697455]
Ronchetti S, Zollo O, Bruscoli S, et al. GITR, a member of the TNF receptor superfamily, is costimulatory to mouse T lymphocyte subpopulations. Eur J Immunol 2004; 34(3): 613-22.
[] [PMID: 14991590]
Mahmud SA, Manlove LS, Schmitz HM, et al. Costimulation via the tumor-necrosis factor receptor superfamily couples TCR signal strength to the thymic differentiation of regulatory T cells. Nat Immunol 2014; 15(5): 473-81.
[] [PMID: 24633226]
Kwan WH, van der Touw W, Heeger PS. Complement regulation of T cell immunity. Immunol Res 2012; 54(1-3): 247-53.
[] [PMID: 22477527]
Kobayashi K, Kaneda K, Kasama T. Immunopathogenesis of delayed-type hypersensitivity. Microsc Res Tech 2001; 53(4): 241-5.
[] [PMID: 11340669]
Rush JS, Hodgkin PD. B cells activated via CD40 and IL-4 undergo a division burst but require continued stimulation to maintain division, survival and differentiation. Eur J Immunol 2001; 31(4): 1150-9.
[<1150:AID-IMMU1150>3.0.CO;2-V] [PMID: 11298340]
Yuan X, Paez-Cortez J, Schmitt-Knosalla I, et al. A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy. J Exp Med 2008; 205(13): 3133-44.
[] [PMID: 19047438]
Wood KJ, Sakaguchi S. Regulatory T cells in transplantation tolerance. Nat Rev Immunol 2003; 3(3): 199-210.
[] [PMID: 12658268]
Saito S, Matsumiya G, Fukushima N, et al. Successful treatment of cardiogenic shock caused by humoral cardiac allograft rejection. Circ J 2009; 73(5): 970-3.
[] [PMID: 19088395]
Ingulli E. Mechanism of cellular rejection in transplantation. Pediatr Nephrol 2010; 25(1): 61-74.
[] [PMID: 21476231]
Mengel M, Sis B, Haas M, et al. Banff 2011 Meeting report: New concepts in antibody-mediated rejection. Am J Transplant 2012; 12(3): 563-70.
[] [PMID: 22300494]
Siedlecki A, Irish W, Brennan DC. Delayed graft function in the kidney transplant. Am J Transplant 2011; 11(11): 2279-96.
[] [PMID: 21929642]
Christians U, Klawitter J, Klawitter J, Brunner N, Schmitz V. Biomarkers of immunosuppressant organ toxicity after transplantation: Status, concepts and misconceptions. Expert Opin Drug Metab Toxicol 2011; 7(2): 175-200.
[] [PMID: 21241200]
Hartono C, Muthukumar T, Suthanthiran M. Immunosuppressive drug therapy. Cold Spring Harb Perspect Med 2013; 3(9)a015487
[] [PMID: 24003247]
Gaber AO, First MR, Tesi RJ, et al. Results of the double-blind, randomized, multicenter, phase III clinical trial of Thymoglobulin versus Atgam in the treatment of acute graft rejection episodes after renal transplantation. Transplantation 1998; 66(1): 29-37.
[] [PMID: 9679818]
Brennan DC, Flavin K, Lowell JA, et al. A randomized, double-blinded comparison of Thymoglobulin versus Atgam for induction immunosuppressive therapy in adult renal transplant recipients. Transplantation 1999; 67(7): 1011-8.
[] [PMID: 10221486]
Carrier M, White M, Perrault LP, et al. A 10-year experience with intravenous thymoglobuline in induction of immunosuppression following heart transplantation. J Heart Lung Transplant 1999; 18(12): 1218-23.
[] [PMID: 10612381]
Eason JD, Loss GE, Blazek J, Nair S, Mason AL. Steroid-free liver transplantation using rabbit antithymocyte globulin induction: results of a prospective randomized trial. Liver Transpl 2001; 7(8): 693-7.
[] [PMID: 11510013]
Mueller TF. Mechanisms of action of thymoglobulin. Transplantation 2007; 84: S5-S10.
Webster AC, Playford EG, Higgins G, Chapman JR, Craig JC. Interleukin 2 receptor antagonists for renal transplant recipients: A meta-analysis of randomized trials. Transplantation 2004; 77(2): 166-76.
[] [PMID: 14742976]
Webster AC, Ruster LP, McGee R, et al. Interleukin 2 receptor antagonists for kidney transplant recipients. Cochrane Database Syst Rev 2010; (1): CD003897
[] [PMID: 20091551]
Hanaway MJ, Woodle ES, Mulgaonkar S, et al. Alemtuzumab induction in renal transplantation. N Engl J Med 2011; 364(20): 1909-19.
[] [PMID: 21591943]
Tarantino A, Montagnino G, Ponticelli C. Corticosteroids in kidney transplant recipients. Safety issues and timing of discontinuation. Drug Saf 1995; 13(3): 145-56.
[] [PMID: 7495501]
Tiede I, Fritz G, Strand S, et al. CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest 2003; 111(8): 1133-45.
[] [PMID: 12697733]
Bansal SB, Saxena V, Pokhariyal S, et al. Comparison of azathioprine with mycophenolate mofetil in a living donor kidney transplant programme. Indian J Nephrol 2011; 21(4): 258-63.
[] [PMID: 22022086]
Olyaei AJ, de Mattos AM, Bennett WM. Nephrotoxicity of immunosuppressive drugs: New insight and preventive strategies. Curr Opin Crit Care 2001; 7(6): 384-9.
[] [PMID: 11805539]
Merville P. Combating chronic renal allograft dysfunction: Optimal immunosuppressive regimens. Drugs 2005; 65(5): 615-31.
[] [PMID: 15748097]
Flechner SM, Kobashigawa J, Klintmalm G. Calcineurin inhibitor-sparing regimens in solid organ transplantation: Focus on improving renal function and nephrotoxicity. Clin Transplant 2008; 22(1): 1-15.
[PMID: 18217899]
Watts RW. Some regulatory and integrative aspects of purine nucleotide biosynthesis and its control: An overview. Adv Enzyme Regul 1983; 21: 33-51.
[] [PMID: 6152730]
Nart A, Sipahi S, Aykas A, Uslu A, Hoşcoşkun C, Toz H. Efficacy and safety of enteric-coated mycophenolate sodium in de novo and maintenance renal transplant patients. Transplant Proc 2008; 40(1): 189-92.
[] [PMID: 18261583]
Ding C, Xue W, Tian P, et al. Outcomes of standard dose EC-MPS with low exposure to CsA in DCD renal transplantation recipients with DGF. Int J Clin Pract Suppl 2015; 183: 8-15.
[] [PMID: 26176940]
Sobiak J, Resztak M, Głyda M, Szczepaniak P, Chrzanowska M. Pharmacokinetics of mycophenolate sodium co-administered with tacrolimus in the first year after renal transplantation. Eur J Drug Metab Pharmacokinet 2016; 41(4): 331-8.
[] [PMID: 25663618]
Schuurman HJ, Cottens S, Fuchs S, et al. SDZ RAD, a new rapamycin derivative: Synergism with cyclosporine. Transplantation 1997; 64(1): 32-5.
[] [PMID: 9233697]
Schuler W, Sedrani R, Cottens S, et al. SDZ RAD, a new rapamycin derivative: Pharmacological properties in vitro and in vivo. Transplantation 1997; 64(1): 36-42.
[] [PMID: 9233698]
Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 2012; 149(2): 274-93.
[] [PMID: 22500797]
Jin YP, Valenzuela NM, Ziegler ME, Rozengurt E, Reed EF. Everolimus inhibits anti-HLA I antibody-mediated endothelial cell signaling, migration and proliferation more potently than sirolimus. Am J Transplant 2014; 14(4): 806-19.
[] [PMID: 24580843]
Vincenti F, Charpentier B, Vanrenterghem Y, et al. A phase III study of belatacept-based immunosuppression regimens versus cyclosporine in renal transplant recipients (BENEFIT study). Am J Transplant 2010; 10(3): 535-46.
[] [PMID: 20415897]
Vincenti F, Larsen CP, Alberu J, et al. Three-year outcomes from BENEFIT, a randomized, active-controlled, parallel-group study in adult kidney transplant recipients. Am J Transplant 2012; 12(1): 210-7.
[] [PMID: 21992533]
Vincenti F, Rostaing L, Grinyo J, et al. Belatacept and long-term outcomes in kidney transplantation. N Engl J Med 2016; 374(4): 333-43.
[] [PMID: 26816011]
Newell KA, Mehta AK, Larsen CP, et al. Lessons learned: Early termination of a randomized trial of calcineurin inhibitor and corticosteroid avoidance using belatacept. Am J Transplant 2017; 17(10): 2712-9.
[] [PMID: 28556519]
de Graav GN, Baan CC, Clahsen-van GMC, et al. A randomized controlled clinical trial comparing belatacept with tacrolimus after de novo kidney transplantation. Transplantation 2017; 101(10): 2571-81.
[] [PMID: 28403127]
Gallagher MP, Kelly PJ, Jardine M, et al. Long-term cancer risk of immunosuppressive regimens after kidney transplantation. J Am Soc Nephrol 2010; 21(5): 852-8.
[] [PMID: 20431040]
Jha V. Post-transplant infections: An ounce of prevention. Indian J Nephrol 2010; 20(4): 171-8.
[] [PMID: 21206677]
Karuthu S, Blumberg EA. Common infections in kidney transplant recipients. Clin J Am Soc Nephrol 2012; 7(12): 2058-70.
[] [PMID: 22977217]
Su J, Xie Q, Xu Y, Li XC, Dai Z. Role of CD8(+) regulatory T cells in organ transplantation. Burns Trauma 2014; 2(1): 18-23.
[] [PMID: 27574642]
Zhang ZX, Yang L, Young KJ, DuTemple B, Zhang L. Identification of a previously unknown antigen-specific regulatory T cell and its mechanism of suppression. Nat Med 2000; 6(7): 782-9.
[] [PMID: 10888927]
Sage PT. Preventing antibody-mediated rejection during transplantation: The potential of Tfr Cells. Transplantation 2018; 102(10): 1597-8.
[] [PMID: 29757906]
Vuddamalay Y, Attia M, Vicente R, et al. Mouse and human CD8(+) CD28(low) regulatory T lymphocytes differentiate in the thymus. Immunology 2016; 148(2): 187-96.
[] [PMID: 26924728]
Zhong H, Liu Y, Xu Z, et al. TGF-β-Induced CD8+CD103+ Regulatory T cells show potent therapeutic effect on chronic graft-versus-Host disease lupus by suppressing B Cells. Front Immunol 2018; 9: 35.
[] [PMID: 29441062]
Churlaud G, Pitoiset F, Jebbawi F, et al. Human and mouse CD8(+)CD25(+)FOXP3(+) Regulatory T Cells at steady state and during interleukin-2 therapy. Front Immunol 2015; 6: 171.
[] [PMID: 25926835]
Liu J, Chen D, Nie GD, Dai Z. CD8(+)CD122(+) T-Cells: A newly emerging regulator with central memory cell phenotypes. Front Immunol 2015; 6: 494.
[] [PMID: 26539191]
Chen W, Ford MS, Young KJ, Zhang L. Infusion of in vitro-generated DN T regulatory cells induces permanent cardiac allograft survival in mice. Transplant Proc 2003; 35(7): 2479-80.
[] [PMID: 14611991]
Sage PT, Sharpe AH. T follicular regulatory cells in the regulation of B cell responses. Trends Immunol 2015; 36(7): 410-8.
[] [PMID: 26091728]
Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M. Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases. J Immunol 1995; 155(3): 1151-64.
[PMID: 7636184]
Hori S, Nomura T, Sakaguchi S. Control of regulatory T cell development by the transcription factor Foxp3. Science 2003; 299(5609): 1057-61.
[] [PMID: 12522256]
Fontenot JD, Gavin MA, Rudensky AY. Foxp3 programs the development and function of CD4+CD25+ regulatory T cells. Nat Immunol 2003; 4(4): 330-6.
[] [PMID: 12612578]
de la Rosa M, Rutz S, Dorninger H, Scheffold A. Interleukin-2 is essential for CD4+CD25+ regulatory T cell function. Eur J Immunol 2004; 34(9): 2480-8.
[] [PMID: 15307180]
Pandiyan P, Zheng L, Ishihara S, Reed J, Lenardo MJ. CD4+CD25+Foxp3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells. Nat Immunol 2007; 8(12): 1353-62.
[] [PMID: 17982458]
Klein M, Bopp T. Cyclic AMP represents a crucial component of treg cell-mediated immune regulation. Front Immunol 2016; 7: 315.
[] [PMID: 27621729]
Kobie JJ, Shah PR, Yang L, Rebhahn JA, Fowell DJ, Mosmann TR. T regulatory and primed uncommitted CD4 T cells express CD73, which suppresses effector CD4 T cells by converting 5′-adenosine monophosphate to adenosine. J Immunol 2006; 177(10): 6780-6.
[] [PMID: 17082591]
Deaglio S, Dwyer KM, Gao W, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med 2007; 204(6): 1257-65.
[] [PMID: 17502665]
Hara M, Kingsley CI, Niimi M, et al. IL-10 is required for regulatory T cells to mediate tolerance to alloantigens in vivo. J Immunol 2001; 166(6): 3789-96.
[] [PMID: 11238621]
Collison LW, Workman CJ, Kuo TT, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function. Nature 2007; 450(7169): 566-9.
[] [PMID: 18033300]
Piccirillo CA, Letterio JJ, Thornton AM, et al. CD4(+)CD25(+) regulatory T cells can mediate suppressor function in the absence of transforming growth factor beta1 production and responsiveness. J Exp Med 2002; 196(2): 237-46.
[] [PMID: 12119348]
Cao X, Cai SF, Fehniger TA, et al. Granzyme B and perforin are important for regulatory T cell-mediated suppression of tumor clearance. Immunity 2007; 27(4): 635-46.
[] [PMID: 17919943]
Cederbom L, Hall H, Ivars F. CD4+CD25+ regulatory T cells down-regulate co-stimulatory molecules on antigen-presenting cells. Eur J Immunol 2000; 30(6): 1538-43.
[<1538:AID-IMMU1538>3.0.CO;2-X] [PMID: 10898488]
Smyth LA, Ratnasothy K, Tsang JY, et al. CD73 expression on extracellular vesicles derived from CD4+ CD25+ Foxp3+ T cells contributes to their regulatory function. Eur J Immunol 2013; 43(9): 2430-40.
[] [PMID: 23749427]
Hoffmann P, Boeld TJ, Eder R, et al. Isolation of CD4+CD25+ regulatory T cells for clinical trials. Biol Blood Marrow Transplant 2006; 12(3): 267-74.
[] [PMID: 16503495]
Di Ianni M, Del Papa B, Zei T, et al. T regulatory cell separation for clinical application. Transfus Apheresis Sci 2012; 47(2): 213-6.
[] [PMID: 22795999]
Tang Q, Bluestone JA. Regulatory T-cell therapy in transplantation: Moving to the clinic. Cold Spring Harb Perspect Med 2013; 3(11): 3.
[] [PMID: 24186492]
Hippen KL, Merkel SC, Schirm DK, et al. Massive ex vivo expansion of human natural regulatory T cells (T(regs)) with minimal loss of in vivo functional activity. Sci Transl Med 2011; 3(83)83ra41
[] [PMID: 21593401]
Scottà C, Esposito M, Fazekasova H, et al. Differential effects of rapamycin and retinoic acid on expansion, stability and suppressive qualities of human CD4(+)CD25(+)FOXP3(+) T regulatory cell subpopulations. Haematologica 2013; 98(8): 1291-9.
[] [PMID: 23242600]
Putnam AL, Safinia N, Medvec A, et al. Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for use in transplantation. Am J Transplant 2013; 13(11): 3010-20.
[] [PMID: 24102808]
Trzonkowski P, Bieniaszewska M, Juścińska J, et al. First-in-man clinical results of the treatment of patients with graft versus host disease with human ex vivo expanded CD4+CD25+CD127- T regulatory cells. Clin Immunol 2009; 133(1): 22-6.
[] [PMID: 19559653]
Todo S, Yamashita K, Goto R, et al. A pilot study of operational tolerance with a regulatory T-cell-based cell therapy in living donor liver transplantation. Hepatology 2016; 64(2): 632-43.
[] [PMID: 26773713]
Chavez JC, Bachmeier C, Kharfan-Dabaja MA. CAR T-cell therapy for B-cell lymphomas: Clinical trial results of available products. Ther Adv Hematol 2019; 102040620719841581
[] [PMID: 31019670]
Schwartz JD. Tisagenlecleucel in diffuse large B-Cell lymphoma. N Engl J Med 2019; 380(16): 1585-6.
[] [PMID: 30995383]
González-Galarza FF, Takeshita LY, Santos EJ, et al. Allele frequency net 2015 update: New features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res 2015; 43: D784-8.
[] [PMID: 25414323]
Zachary AA, Leffell MS. HLA mismatching strategies for solid organ transplantation - A balancing act. Front Immunol 2016; 7: 575.
[] [PMID: 28003816]
MacDonald KG, Hoeppli RE, Huang Q, et al. Alloantigen-specific regulatory T cells generated with a chimeric antigen receptor. J Clin Invest 2016; 126(4): 1413-24.
[] [PMID: 26999600]
Noyan F, Zimmermann K, Hardtke-Wolenski M, et al. Prevention of allograft rejection by use of regulatory T Cells with an MHC-specific chimeric antigen receptor. Am J Transplant 2017; 17(4): 917-30.
[] [PMID: 27997080]
DeFrancesco L. CAR-T cell therapy seeks strategies to harness cytokine storm. Nat Biotechnol 2014; 32(7): 604.
[] [PMID: 25004212]
Brudno JN, Kochenderfer JN. Recent advances in CAR T-cell toxicity: Mechanisms, manifestations and management. Blood Rev 2019; 34: 45-55.
[] [PMID: 30528964]
Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK. Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity 2002; 16(2): 219-30.
[] [PMID: 11869683]
Katz SI, Parker D, Turk JL. B-cell suppression of delayed hypersensitivity reactions. Nature 1974; 251(5475): 550-1.
[] [PMID: 4547522]
Neta R, Salvin SB. Specific suppression of delayed hypersensitivity: The possible presence of a suppressor B cell in the regulation of delayed hypersensitivity. J Immunol 1974; 113(6): 1716-25.
[PMID: 4279260]
Marino J, Paster JT, Trowell A, et al. B Cell depletion with an Anti-CD20 antibody enhances alloreactive memory T Cell Responses after transplantation. Am J Transplant 2016; 16(2): 672-8.
[] [PMID: 26552037]
Carter NA, Rosser EC, Mauri C. Interleukin-10 produced by B cells is crucial for the suppression of Th17/Th1 responses, induction of T regulatory type 1 cells and reduction of collagen-induced arthritis. Arthritis Res Ther 2012; 14(1): R32.
[] [PMID: 22315945]
Flores-Borja F, Bosma A, Ng D, et al. CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci Transl Med 2013; 5(173)173ra23
[] [PMID: 23427243]
Sun JB, Flach CF, Czerkinsky C, Holmgren J. B lymphocytes promote expansion of regulatory T cells in oral tolerance: Powerful induction by antigen coupled to cholera toxin B subunit. J Immunol 2008; 181(12): 8278-87.
[] [PMID: 19050244]
Tadmor T, Zhang Y, Cho HM, Podack ER, Rosenblatt JD. The absence of B lymphocytes reduces the number and function of T-regulatory cells and enhances the anti-tumor response in a murine tumor model. Cancer Immunol Immunother 2011; 60(5): 609-19.
[] [PMID: 21253724]
Yoshizaki A, Miyagaki T, DiLillo DJ, et al. Regulatory B cells control T-cell autoimmunity through IL-21-dependent cognate interactions. Nature 2012; 491(7423): 264-8.
[] [PMID: 23064231]
Mann MK, Maresz K, Shriver LP, Tan Y, Dittel BN. B cell regulation of CD4+CD25+ T regulatory cells and IL-10 via B7 is essential for recovery from experimental autoimmune encephalomyelitis. J Immunol 2007; 178(6): 3447-56.
[] [PMID: 17339439]
Rosser EC, Blair PA, Mauri C. Cellular targets of regulatory B cell-mediated suppression. Mol Immunol 2014; 62(2): 296-304.
[] [PMID: 24556109]
Carter NA, Vasconcellos R, Rosser EC, et al. Mice lacking endogenous IL-10-producing regulatory B cells develop exacerbated disease and present with an increased frequency of Th1/Th17 but a decrease in regulatory T cells. J Immunol 2011; 186(10): 5569-79.
[] [PMID: 21464089]
Shen P, Roch T, Lampropoulou V, et al. IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases. Nature 2014; 507(7492): 366-70.
[] [PMID: 24572363]
Wang RX, Yu CR, Dambuza IM, et al. Interleukin-35 induces regulatory B cells that suppress autoimmune disease. Nat Med 2014; 20(6): 633-41.
[] [PMID: 24743305]
Tian J, Zekzer D, Hanssen L, Lu Y, Olcott A, Kaufman DL. Lipopolysaccharide-activated B cells down-regulate Th1 immunity and prevent autoimmune diabetes in nonobese diabetic mice. J Immunol 2001; 167(2): 1081-9.
[] [PMID: 11441119]
Parekh VV, Prasad DV, Banerjee PP, Joshi BN, Kumar A, Mishra GC. B cells activated by lipopolysaccharide, but not by anti-Ig and anti-CD40 antibody, induce anergy in CD8+ T cells: Role of TGF-beta 1. J Immunol 2003; 170(12): 5897-911.
[] [PMID: 12794116]
Bosma A, Abdel-Gadir A, Isenberg DA, Jury EC, Mauri C. Lipid-antigen presentation by CD1d(+) B cells is essential for the maintenance of invariant natural killer T cells. Immunity 2012; 36(3): 477-90.
[] [PMID: 22406267]
Le Texier L, Thebault P, Lavault A, et al. Long-term allograft tolerance is characterized by the accumulation of B cells exhibiting an inhibited profile. Am J Transplant 2011; 11(3): 429-38.
[] [PMID: 21114655]
Durand J, Huchet V, Merieau E, et al. Regulatory B Cells with a partial defect in CD40 signaling and overexpressing granzyme B transfer allograft tolerance in rodents. J Immunol 2015; 195(10): 5035-44.
[] [PMID: 26432892]
Moreau A, Blair PA, Chai JG, et al. Transitional-2 B cells acquire regulatory function during tolerance induction and contribute to allograft survival. Eur J Immunol 2015; 45(3): 843-53.
[] [PMID: 25408265]
Ding Q, Yeung M, Camirand G, et al. Regulatory B cells are identified by expression of TIM-1 and can be induced through TIM-1 ligation to promote tolerance in mice. J Clin Invest 2011; 121(9): 3645-56.
[] [PMID: 21821911]
Xiao S, Brooks CR, Zhu C, et al. Defect in regulatory B-cell function and development of systemic autoimmunity in T-cell Ig mucin 1 (Tim-1) mucin domain-mutant mice. Proc Natl Acad Sci USA 2012; 109(30): 12105-10.
[] [PMID: 22773818]
Xiao S, Brooks CR, Sobel RA, Kuchroo VK. Tim-1 is essential for induction and maintenance of IL-10 in regulatory B cells and their regulation of tissue inflammation. J Immunol 2015; 194(4): 1602-8.
[] [PMID: 25582854]
Yeung MY, Ding Q, Brooks CR, et al. TIM-1 signaling is required for maintenance and induction of regulatory B cells. Am J Transplant 2015; 15(4): 942-53.
[] [PMID: 25645598]
Dambuza IM, He C, Choi JK, et al. IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease. Nat Commun 2017; 8(1): 719.
[] [PMID: 28959012]
Hirose T, Tanaka Y, Tanaka A, et al. PD-L1/PD-L2-expressing B-1 cells inhibit alloreactive T cells in mice. PLoS One 2017; 12(6)e0178765
[] [PMID: 28570665]
Clatworthy MR, Watson CJ, Plotnek G, et al. B-cell-depleting induction therapy and acute cellular rejection. N Engl J Med 2009; 360(25): 2683-5.
[] [PMID: 19535812]
Cherukuri A, Rothstein DM, Clark B, et al. Immunologic human renal allograft injury associates with an altered IL-10/TNF-α expression ratio in regulatory B cells. J Am Soc Nephrol 2014; 25(7): 1575-85.
[] [PMID: 24610932]
Chesneau M, Michel L, Dugast E, et al. Tolerant kidney transplant patients produce B cells with regulatory properties. J Am Soc Nephrol 2015; 26(10): 2588-98.
[] [PMID: 25644114]
Bankó Z, Pozsgay J, Szili D, et al. Induction and differentiation of IL-10-producing regulatory B cells from healthy blood donors and Rheumatoid Arthritis patients. J Immunol 2017; 198(4): 1512-20.
[] [PMID: 28087671]
Steinman RM, Cohn ZA. Identification of a novel cell type in peripheral lymphoid organs of mice. I. Morphology, quantitation, tissue distribution. J Exp Med 1973; 137(5): 1142-62.
[] [PMID: 4573839]
Fujita S, Seino K, Sato K, et al. Regulatory dendritic cells act as regulators of acute lethal systemic inflammatory response. Blood 2006; 107(9): 3656-64.
[] [PMID: 16410444]
Steinman RM, Hawiger D, Nussenzweig MC. Tolerogenic dendritic cells. Annu Rev Immunol 2003; 21: 685-711.
[] [PMID: 12615891]
Schmidt SV, Nino-Castro AC, Schultze JL. Regulatory dendritic cells: There is more than just immune activation. Front Immunol 2012; 3: 274.
[] [PMID: 22969767]
Amodio G, Gregori S. Human tolerogenic DC-10: Perspectives for clinical applications. Transplant Res 2012; 1(1): 14.
[] [PMID: 23369527]
Horton C, Shanmugarajah K, Fairchild PJ. Harnessing the properties of dendritic cells in the pursuit of immunological tolerance. Biomed J 2017; 40(2): 80-93.
[] [PMID: 28521905]
Cai S, Hou J, Fujino M, et al. iPSC-Derived regulatory dendritic cells inhibit allograft rejection by generating alloantigen-specific regulatory T cells. Stem Cell Reports 2017; 8(5): 1174-89.
[] [PMID: 28434942]
Dixon KO, van der Kooij SW, Vignali DA, van Kooten C. Human tolerogenic dendritic cells produce IL-35 in the absence of other IL-12 family members. Eur J Immunol 2015; 45(6): 1736-47.
[] [PMID: 25820702]
Svajger U, Rozman P. Tolerogenic dendritic cells: Molecular and cellular mechanisms in transplantation. J Leukoc Biol 2014; 95(1): 53-69.
[] [PMID: 24108704]
Raker VK, Domogalla MP, Steinbrink K. Tolerogenic dendritic cells for regulatory T cell induction in man. Front Immunol 2015; 6: 569.
[] [PMID: 26617604]
Giannoukakis N, Phillips B, Finegold D, Harnaha J, Trucco M. Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients. Diabetes Care 2011; 34(9): 2026-32.
[] [PMID: 21680720]
Morelli AE, Thomson AW. Tolerogenic dendritic cells and the quest for transplant tolerance. Nat Rev Immunol 2007; 7(8): 610-21.
[] [PMID: 17627284]
Yang J, Bernier SM, Ichim TE, et al. LF15-0195 generates tolerogenic dendritic cells by suppression of NF-kappaB signaling through inhibition of IKK activity. J Leukoc Biol 2003; 74(3): 438-47.
[] [PMID: 12949248]
Moreau A, Varey E, Bériou G, et al. Tolerogenic dendritic cells and negative vaccination in transplantation: From rodents to clinical trials. Front Immunol 2012; 3: 218.
[] [PMID: 22908013]
Pêche H, Trinité B, Martinet B, Cuturi MC. Prolongation of heart allograft survival by immature dendritic cells generated from recipient type bone marrow progenitors. Am J Transplant 2005; 5(2): 255-67.
[] [PMID: 15643985]
Divito SJ, Wang Z, Shufesky WJ, et al. Endogenous dendritic cells mediate the effects of intravenously injected therapeutic immunosuppressive dendritic cells in transplantation. Blood 2010; 116(15): 2694-705.
[] [PMID: 20576812]
Garrovillo M, Ali A, Oluwole SF. Indirect allorecognition in acquired thymic tolerance: Induction of donor-specific tolerance to rat cardiac allografts by allopeptide-pulsed host dendritic cells. Transplantation 1999; 68(12): 1827-34.
[] [PMID: 10628758]
Jauregui-Amezaga A, Cabezón R, Ramírez-Morros A, et al. Intraperitoneal administration of autologous tolerogenic dendritic cells for refractory Crohn’s Disease: A phase I study. J Crohn’s Colitis 2015; 9(12): 1071-8.
[] [PMID: 26303633]
Benham H, Nel HJ, Law SC, et al. Citrullinated peptide dendritic cell immunotherapy in HLA risk genotype-positive rheumatoid arthritis patients. Sci Transl Med 2015; 7(290)290ra87
Bell GM, Anderson AE, Diboll J, et al. Autologous tolerogenic dendritic cells for rheumatoid and inflammatory arthritis. Ann Rheum Dis 2017; 76(1): 227-34.
[] [PMID: 27117700]
Marín E, Cuturi MC, Moreau A. Tolerogenic dendritic cells in solid organ transplantation: Where do we stand? Front Immunol 2018; 9: 274.
[] [PMID: 29520275]
Thomson AW, Zahorchak AF, Ezzelarab MB, Butterfield LH, Lakkis FG, Metes DM. Prospective clinical testing of regulatory dendritic cells in organ transplantation. Front Immunol 2016; 7: 15.
[] [PMID: 26858719]
Chabannes D, Hill M, Merieau E, et al. A role for heme oxygenase-1 in the immunosuppressive effect of adult rat and human mesenchymal stem cells. Blood 2007; 110(10): 3691-4.
[] [PMID: 17684157]
Franquesa M, Hoogduijn MJ, Reinders ME, et al. Mesenchymal Stem Cells in Solid Organ Transplantation (MiSOT) fourth meeting: Lessons learned from first clinical trials. Transplantation 2013; 96(3): 234-8.
[] [PMID: 23759879]
Tan J, Wu W, Xu X, et al. Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: A randomized controlled trial. JAMA 2012; 307(11): 1169-77.
[] [PMID: 22436957]
Riquelme P, Tomiuk S, Kammler A, et al. IFN-γ-induced iNOS expression in mouse regulatory macrophages prolongs allograft survival in fully immunocompetent recipients. Mol Ther 2013; 21(2): 409-22.
[] [PMID: 22929659]
Hutchinson JA, Riquelme P, Sawitzki B, et al. Cutting Edge: Immunological consequences and trafficking of human regulatory macrophages administered to renal transplant recipients. J Immunol 2011; 187(5): 2072-8.
[] [PMID: 21804023]
Gabrilovich DI, Nagaraj S. Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 2009; 9(3): 162-74.
[] [PMID: 19197294]

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