Subscribe to RSS
DOI: 10.1055/s-0038-1661336
Cell-Based Therapies in Vascularized Composite Allotransplantation
Funding and Financial Disclosures The authors have no financial disclosures to declare and there was no funding obtained for the production of this article.Publication History
27 November 2017
28 April 2018
Publication Date:
26 June 2018 (online)
![](https://www.thieme-connect.de/media/jrm/201808/lookinside/thumbnails/10-1055-s-0038-1661336_170340-1.jpg)
Abstract
Background Dendritic cells (DCs) are bone marrow-derived, professional antigen-presenting cells with tolerogenic function. The ability of DCs to regulate alloantigen-specific T cell responses and to promote tolerance has aligned them ideally for a role in vascularized composite allotransplantation (VCA). In this study, we summarize the current evidence for DC therapies for tolerance induction to alleviate the requirement for chronic immunosuppression.
Method A comprehensive and structured review of manuscripts published on VCA was performed using the MEDLINE and PubMed databases. All eligible studies published from the year 2000 to 2017 were included in the final results.
Result Nineteen original preclinical and clinical studies that employed cell therapy for VCA were included in this review. In vivo DC therapy was found to direct the alloimmune response toward either transplant rejection or tolerance in VCA models. While injection of mature DCs rapidly increases T-cell activity in humans and promotes transplant rejection, the injection of immature DCs acts as an immunosuppressant and inhibits T-cell activity. In addition to immature DCs, mesenchymal stem cells were also found to have a positive effect on allotransplantation of solid organs and bone marrow via cytokine expression which decreases the alloreactive effector lymphocytes and increases CD4+/CD25+/FoxP3 Tregs. Despite the promising findings, the efficacy of cell-based therapies varies greatly across studies, partly due to different methods of cell isolation and purification techniques, source, route and timing of administration, and combination immunosuppressive therapy.
Conclusion Additional research is needed to evaluate the efficacy and safety of DC and other cell-based therapeutic measures in human allotransplant recipients. Future direction will focus on the development of novel methods to reduce immunosuppression and develop more individualized management, as well as the clinical application of basic research in the mechanisms of immunologic tolerance.
Keywords
tolerogenic dendritic cells - dendritic cells - composite tissue allotransplantation - vascularized composite allotransplantation - immunosuppressive - cell-based therapy - immune tolerance - transplantation - immature DCs - DCs-
References
- 1 Petit F, Minns AB, Dubernard JM, Hettiaratchy S, Lee WP. Composite tissue allotransplantation and reconstructive surgery: first clinical applications. Ann Surg 2003; 237 (01) 19-25
- 2 Lechler RI, Sykes M, Thomson AW, Turka LA. Organ transplantation--how much of the promise has been realized?. Nat Med 2005; 11 (06) 605-613
- 3 Swearingen B, Ravindra K, Xu H, Wu S, Breidenbach WC, Ildstad ST. Science of composite tissue allotransplantation. Transplantation 2008; 86 (05) 627-635
- 4 Solari MG, Srinivasan S, Boumaza I. , et al. Marginal mass islet transplantation with autologous mesenchymal stem cells promotes long-term islet allograft survival and sustained normoglycemia. J Autoimmun 2009; 32 (02) 116-124
- 5 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 (05) 1142-1162
- 6 Legge KL, Gregg RK, Maldonado-Lopez R. , et al. On the role of dendritic cells in peripheral T cell tolerance and modulation of autoimmunity. J Exp Med 2002; 196 (02) 217-227
- 7 Shortman K, Naik SH. Steady-state and inflammatory dendritic-cell development. Nat Rev Immunol 2007; 7 (01) 19-30
- 8 Jung YJ, Ju SY, Yoo ES. , et al. MSC-DC interactions: MSC inhibit maturation and migration of BM-derived DC. Cytotherapy 2007; 9 (05) 451-458
- 9 Morelli AE, Thomson AW. Tolerogenic dendritic cells and the quest for transplant tolerance. Nat Rev Immunol 2007; 7 (08) 610-621
- 10 Cools N, Ponsaerts P, Van Tendeloo VF, Berneman ZN. Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells. J Leukoc Biol 2007; 82 (06) 1365-1374
- 11 Thomson AW, Sacks JM, Kuo YR. , et al. Dendritic cell therapy in composite tissue allotransplantation. Transplant Proc 2009; 41 (02) 537-538
- 12 Lechler R, Ng WF, Steinman RM. Dendritic cells in transplantation--friend or foe?. Immunity 2001; 14 (04) 357-368
- 13 Ezzelarab M, Thomson AW. Tolerogenic dendritic cells and their role in transplantation. Semin Immunol 2011; 23 (04) 252-263
- 14 Leishman AJ, Silk KM, Fairchild PJ. Pharmacological manipulation of dendritic cells in the pursuit of transplantation tolerance. Curr Opin Organ Transplant 2011; 16 (04) 372-378
- 15 van Kooten C, Lombardi G, Gelderman KA. , et al. Dendritic cells as a tool to induce transplantation tolerance: obstacles and opportunities. Transplantation 2011; 91 (01) 2-7
- 16 Lu L, Li W, Fu F. , et al. Blockade of the CD40-CD40 ligand pathway potentiates the capacity of donor-derived dendritic cell progenitors to induce long-term cardiac allograft survival. Transplantation 1997; 64 (12) 1808-1815
- 17 Thomson AW, Lu L, Subbotin VM. , et al. In vitro propagation and homing of liver-derived dendritic cell progenitors to lymphoid tissues of allogeneic recipients. Implications for the establishment and maintenance of donor cell chimerism following liver transplantation. Transplantation 1995; 59 (04) 544-551
- 18 Terness P, Kleist C, Simon H. , et al. Mitomycin C-treated antigen-presenting cells as a tool for control of allograft rejection and autoimmunity: from bench to bedside. Hum Immunol 2009; 70 (07) 506-512
- 19 Oluwole OO, Depaz HA, Gopinathan R. , et al. Indirect allorecognition in acquired thymic tolerance: induction of donor-specific permanent acceptance of rat islets by adoptive transfer of allopeptide-pulsed host myeloid and thymic dendritic cells. Diabetes 2001; 50 (07) 1546-1552
- 20 Mirenda V, Berton I, Read J. , et al. Modified dendritic cells coexpressing self and allogeneic major histocompatability complex molecules: an efficient way to induce indirect pathway regulation. J Am Soc Nephrol 2004; 15 (04) 987-997
- 21 Sacks JM, Kuo YR, Taieb A. , et al. Prolongation of composite tissue allograft survival by immature recipient dendritic cells pulsed with donor antigen and transient low-dose immunosuppression. Plast Reconstr Surg 2008; 121 (01) 37-49
- 22 Kuo YR, Huang CW, Goto S. , et al. Alloantigen-pulsed host dendritic cells induce T-cell regulation and prolong allograft survival in a rat model of hindlimb allotransplantation. J Surg Res 2009; 153 (02) 317-325
- 23 Ikeguchi R, Sacks JM, Unadkat JV. , et al. Long-term survival of limb allografts induced by pharmacologically conditioned, donor alloantigen-pulsed dendritic cells without maintenance immunosuppression. Transplantation 2008; 85 (02) 237-246
- 24 Horibe EK, Sacks J, Unadkat J. , et al. Rapamycin-conditioned, alloantigen-pulsed dendritic cells promote indefinite survival of vascularized skin allografts in association with T regulatory cell expansion. Transpl Immunol 2008; 18 (04) 307-318
- 25 Eun SC, Baek RM, Park CG. Prolongation of the rat composite tissue allograft survival by the combination of tolerogenic immature dendritic cells and short-term treatment with FK506. Transplant Proc 2013; 45 (05) 1792-1796
- 26 Liu F, Luo X, Lan S. , et al. Immunosuppression with a combination of triptolide and cyclosporin A in rat vascularized groin flap allotransplantation. Plast Reconstr Surg 2013; 131 (03) 343e-350e
- 27 Wang Y, Zheng Z, Zhu X. , et al. The amelioration of composite tissue allograft rejection by TIM-3-modified dendritic cell: regulation of the balance of regulatory and effector T cells. Immunol Lett 2016; 169: 15-22
- 28 Yamano T, Watanabe S, Hasegawa H. , et al. Ex vivo-expanded DCs induce donor-specific central and peripheral tolerance and prolong the acceptance of donor skin grafts. Blood 2011; 117 (09) 2640-2648
- 29 Turnquist HR, Raimondi G, Zahorchak AF, Fischer RT, Wang Z, Thomson AW. Rapamycin-conditioned dendritic cells are poor stimulators of allogeneic CD4+ T cells, but enrich for antigen-specific Foxp3+ T regulatory cells and promote organ transplant tolerance. J Immunol 2007; 178 (11) 7018-7031
- 30 Fischer RT, Turnquist HR, Wang Z, Beer-Stolz D, Thomson AW. Rapamycin-conditioned, alloantigen-pulsed myeloid dendritic cells present donor MHC class I/peptide via the semi-direct pathway and inhibit survival of antigen-specific CD8(+) T cells in vitro and in vivo. Transpl Immunol 2011; 25 (01) 20-26
- 31 Starzl TE, Demetris AJ, Murase N, Trucco M, Thomson AW, Rao AS. The lost chord: microchimerism and allograft survival. Immunol Today 1996; 17 (12) 577-584 , discussion 588
- 32 Kuo YR, Chen CC, Goto S, Lin PY, Wei FC, Chen CL. Mesenchymal stem cells as immunomodulators in a vascularized composite allotransplantation. Clin Dev Immunol 2012; 2012 (12) 854846
- 33 Djouad F, Charbonnier LM, Bouffi C. , et al. Mesenchymal stem cells inhibit the differentiation of dendritic cells through an interleukin-6-dependent mechanism. Stem Cells 2007; 25 (08) 2025-2032
- 34 English K, Barry FP, Mahon BP. Murine mesenchymal stem cells suppress dendritic cell migration, maturation and antigen presentation. Immunol Lett 2008; 115 (01) 50-58
- 35 Li M, Sun K, Welniak LA, Murphy WJ. Immunomodulation and pharmacological strategies in the treatment of graft-versus-host disease. Expert Opin Pharmacother 2008; 9 (13) 2305-2316
- 36 Zhang X, Jiao C, Zhao S. Role of mesenchymal stem cells in immunological rejection of organ transplantation. Stem Cell Rev 2009; 5 (04) 402-409
- 37 English K. Mechanisms of mesenchymal stromal cell immunomodulation. Immunol Cell Biol 2013; 91 (01) 19-26
- 38 Singer NG, Caplan AI. Mesenchymal stem cells: mechanisms of inflammation. Annu Rev Pathol 2011; 6: 457-478
- 39 Bartholomew A, Sturgeon C, Siatskas M. , et al. Mesenchymal stem cells suppress lymphocyte proliferation in vitro and prolong skin graft survival in vivo. Exp Hematol 2002; 30 (01) 42-48
- 40 Melief SM, Zwaginga JJ, Fibbe WE, Roelofs H. Adipose tissue-derived multipotent stromal cells have a higher immunomodulatory capacity than their bone marrow-derived counterparts. Stem Cells Transl Med 2013; 2 (06) 455-463
- 41 Cui L, Yin S, Liu W, Li N, Zhang W, Cao Y. Expanded adipose-derived stem cells suppress mixed lymphocyte reaction by secretion of prostaglandin E2. Tissue Eng 2007; 13 (06) 1185-1195
- 42 Fang B, Song Y, Lin Q. , et al. Human adipose tissue-derived mesenchymal stromal cells as salvage therapy for treatment of severe refractory acute graft-vs.-host disease in two children. Pediatr Transplant 2007; 11 (07) 814-817
- 43 Wan CD, Cheng R, Wang HB, Liu T. Immunomodulatory effects of mesenchymal stem cells derived from adipose tissues in a rat orthotopic liver transplantation model. Hepatobiliary Pancreat Dis Int 2008; 7 (01) 29-33
- 44 Constantin G, Marconi S, Rossi B. , et al. Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. Stem Cells 2009; 27 (10) 2624-2635
- 45 González MA, Gonzalez-Rey E, Rico L, Büscher D, Delgado M. Treatment of experimental arthritis by inducing immune tolerance with human adipose-derived mesenchymal stem cells. Arthritis Rheum 2009; 60 (04) 1006-1019
- 46 Gonzalez-Rey E, Anderson P, González MA, Rico L, Büscher D, Delgado M. Human adult stem cells derived from adipose tissue protect against experimental colitis and sepsis. Gut 2009; 58 (07) 929-939
- 47 Crop MJ, Baan CC, Korevaar SS. , et al. Inflammatory conditions affect gene expression and function of human adipose tissue-derived mesenchymal stem cells. Clin Exp Immunol 2010; 162 (03) 474-486
- 48 Gonzalez-Rey E, Gonzalez MA, Varela N. , et al. Human adipose-derived mesenchymal stem cells reduce inflammatory and T cell responses and induce regulatory T cells in vitro in rheumatoid arthritis. Ann Rheum Dis 2010; 69 (01) 241-248
- 49 Engela AU, Baan CC, Dor FJ, Weimar W, Hoogduijn MJ. On the interactions between mesenchymal stem cells and regulatory T cells for immunomodulation in transplantation. Front Immunol 2012; 3: 126
- 50 Izadpanah R, Trygg C, Patel B. , et al. Biologic properties of mesenchymal stem cells derived from bone marrow and adipose tissue. J Cell Biochem 2006; 99 (05) 1285-1297
- 51 Liu TM, Martina M, Hutmacher DW, Hui JH, Lee EH, Lim B. Identification of common pathways mediating differentiation of bone marrow- and adipose tissue-derived human mesenchymal stem cells into three mesenchymal lineages. Stem Cells 2007; 25 (03) 750-760
- 52 Noël D, Caton D, Roche S. , et al. Cell specific differences between human adipose-derived and mesenchymal-stromal cells despite similar differentiation potentials. Exp Cell Res 2008; 314 (07) 1575-1584
- 53 Bernardo ME, Fibbe WE. Safety and efficacy of mesenchymal stromal cell therapy in autoimmune disorders. Ann N Y Acad Sci 2012; 1266: 107-117
- 54 De Miguel MP, Fuentes-Julián S, Blázquez-Martínez A. , et al. Immunosuppressive properties of mesenchymal stem cells: advances and applications. Curr Mol Med 2012; 12 (05) 574-591
- 55 Figueroa FE, Carrión F, Villanueva S, Khoury M. Mesenchymal stem cell treatment for autoimmune diseases: a critical review. Biol Res 2012; 45 (03) 269-277
- 56 Griffin MD, Ritter T, Mahon BP. Immunological aspects of allogeneic mesenchymal stem cell therapies. Hum Gene Ther 2010; 21 (12) 1641-1655
- 57 Jones BJ, McTaggart SJ. Immunosuppression by mesenchymal stromal cells: from culture to clinic. Exp Hematol 2008; 36 (06) 733-741
- 58 Casiraghi F, Azzollini N, Todeschini M. , et al. Localization of mesenchymal stromal cells dictates their immune or proinflammatory effects in kidney transplantation. Am J Transplant 2012; 12 (09) 2373-2383
- 59 Crop MJ, Baan CC, Korevaar SS, Ijzermans JN, Weimar W, Hoogduijn MJ. Human adipose tissue-derived mesenchymal stem cells induce explosive T-cell proliferation. Stem Cells Dev 2010; 19 (12) 1843-1853
- 60 de Girolamo L, Lucarelli E, Alessandri G. , et al; Italian Mesenchymal Stem Cell Group. Mesenchymal stem/stromal cells: a new “cells as drugs” paradigm. Efficacy and critical aspects in cell therapy. Curr Pharm Des 2013; 19 (13) 2459-2473
- 61 Di Ianni M, Del Papa B, De Ioanni M. , et al. Mesenchymal cells recruit and regulate T regulatory cells. Exp Hematol 2008; 36 (03) 309-318
- 62 Duffy MM, Ritter T, Ceredig R, Griffin MD. Mesenchymal stem cell effects on T-cell effector pathways. Stem Cell Res Ther 2011; 2 (04) 34
- 63 Hong ZF, Huang XJ, Yin ZY, Zhao WX, Wang XM. Immunosuppressive function of bone marrow mesenchymal stem cells on acute rejection of liver allografts in rats. Transplant Proc 2009; 41 (01) 403-409
- 64 Inoue S, Popp FC, Koehl GE. , et al. Immunomodulatory effects of mesenchymal stem cells in a rat organ transplant model. Transplantation 2006; 81 (11) 1589-1595
- 65 Itakura S, Asari S, Rawson J. , et al. Mesenchymal stem cells facilitate the induction of mixed hematopoietic chimerism and islet allograft tolerance without GVHD in the rat. Am J Transplant 2007; 7 (02) 336-346
- 66 Kuo YR, Chen CC, Goto S. , et al. Modulation of immune response and T-cell regulation by donor adipose-derived stem cells in a rodent hind-limb allotransplant model. Plast Reconstr Surg 2011; 128 (06) 661e-672e
- 67 Kuo YR, Goto S, Shih HS. , et al. Mesenchymal stem cells prolong composite tissue allotransplant survival in a swine model. Transplantation 2009; 87 (12) 1769-1777
- 68 Lawitschka A, Ball L, Peters C. Nonpharmacologic treatment of chronic graft-versus-host disease in children and adolescents. Biol Blood Marrow Transplant 2012; 18 (1, Suppl): S74-S81
- 69 Le Blanc K, Frassoni F, Ball L. , et al; Developmental Committee of the European Group for Blood and Marrow Transplantation. Mesenchymal stem cells for treatment of steroid-resistant, severe, acute graft-versus-host disease: a phase II study. Lancet 2008; 371 (9624): 1579-1586
- 70 Pan H, Zhao K, Wang L. , et al. Mesenchymal stem cells enhance the induction of mixed chimerism and tolerance to rat hind-limb allografts after bone marrow transplantation. J Surg Res 2010; 160 (02) 315-324
- 71 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) 1169-1177
- 72 Wu GD, Nolta JA, Jin YS. , et al. Migration of mesenchymal stem cells to heart allografts during chronic rejection. Transplantation 2003; 75 (05) 679-685
- 73 Zhou HP, Yi DH, Yu SQ. , et al. Administration of donor-derived mesenchymal stem cells can prolong the survival of rat cardiac allograft. Transplant Proc 2006; 38 (09) 3046-3051
- 74 Plock JA, Schnider JT, Solari MG, Zheng XX, Gorantla VS. Perspectives on the use of mesenchymal stem cells in vascularized composite allotransplantation. Front Immunol 2013; 4: 175
- 75 Kuo YR, Chen CC, Shih HS. , et al. Prolongation of composite tissue allotransplant survival by treatment with bone marrow mesenchymal stem cells is correlated with T-cell regulation in a swine hind-limb model. Plast Reconstr Surg 2011; 127 (02) 569-579
- 76 Kuo YR, Chen CC, Goto S, Huang YT, Tsai CC, Yang MY. Proteomic analysis in serum of rat hind-limb allograft tolerance induced by immunosuppressive therapy with adipose-derived stem cells. Plast Reconstr Surg 2014; 134 (06) 1213-1223
- 77 Jeong SH, Ji YH, Yoon ES. Immunosuppressive activity of adipose tissue-derived mesenchymal stem cells in a rat model of hind limb allotransplantation. Transplant Proc 2014; 46 (05) 1606-1614
- 78 Cheng HY, Ghetu N, Huang WC. , et al. Syngeneic adipose-derived stem cells with short-term immunosuppression induce vascularized composite allotransplantation tolerance in rats. Cytotherapy 2014; 16 (03) 369-380
- 79 Plock JA, Schnider JT, Schweizer R. , et al. The influence of timing and frequency of adipose-derived mesenchymal stem cell therapy on immunomodulation outcomes after vascularized composite allotransplantation. Transplantation 2017; 101 (01) e1-e11
- 80 Plock JA, Schnider JT, Zhang W. , et al. Adipose- and bone marrow-derived mesenchymal stem cells prolong graft survival in vascularized composite allotransplantation. Transplantation 2015; 99 (09) 1765-1773
- 81 Aksu AE, Horibe E, Sacks J. , et al. Co-infusion of donor bone marrow with host mesenchymal stem cells treats GVHD and promotes vascularized skin allograft survival in rats. Clin Immunol 2008; 127 (03) 348-358
- 82 Kuo YR, Chen CC, Goto S. , et al. Immunomodulatory effects of bone marrow-derived mesenchymal stem cells in a swine hemi-facial allotransplantation model. PLoS One 2012; 7 (04) e35459
- 83 Zhou Y, Shan J, Li Y. , et al. Adoptive transfusion of tolerance dendritic cells prolongs the survival of skin allografts in mice: a systematic review. J Evid Based Med 2013; 6 (02) 90-103
- 84 Eggenhofer E, Benseler V, Kroemer A. , et al. Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion. Front Immunol 2012; 3: 297
- 85 Rombouts WJ, Ploemacher RE. Primary murine MSC show highly efficient homing to the bone marrow but lose homing ability following culture. Leukemia 2003; 17 (01) 160-170
- 86 Wagner W, Horn P, Castoldi M. , et al. Replicative senescence of mesenchymal stem cells: a continuous and organized process. PLoS One 2008; 3 (05) e2213
- 87 Hematti P. Mesenchymal stromal cells and fibroblasts: a case of mistaken identity?. Cytotherapy 2012; 14 (05) 516-521
- 88 Vacanti V, Kong E, Suzuki G, Sato K, Canty JM, Lee T. Phenotypic changes of adult porcine mesenchymal stem cells induced by prolonged passaging in culture. J Cell Physiol 2005; 205 (02) 194-201
- 89 Wagner W, Ho AD, Zenke M. Different facets of aging in human mesenchymal stem cells. Tissue Eng Part B Rev 2010; 16 (04) 445-453
- 90 Berger TG, Schulze-Koops H, Schäfer M, Müller E, Lutz MB. Immature and maturation-resistant human dendritic cells generated from bone marrow require two stimulations to induce T cell anergy in vitro. PLoS One 2009; 4 (08) e6645
- 91 Moreau A, Chiffoleau E, Beriou G. , et al. Superiority of bone marrow-derived dendritic cells over monocyte-derived ones for the expansion of regulatory T cells in the macaque. Transplantation 2008; 85 (09) 1351-1356
- 92 Ueno H, Schmitt N, Klechevsky E. , et al. Harnessing human dendritic cell subsets for medicine. Immunol Rev 2010; 234 (01) 199-212
- 93 Lutz MB, Suri RM, Niimi M. , et al. Immature dendritic cells generated with low doses of GM-CSF in the absence of IL-4 are maturation resistant and prolong allograft survival in vivo. Eur J Immunol 2000; 30 (07) 1813-1822
- 94 Chitta S, Santambrogio L, Stern LJ. GMCSF in the absence of other cytokines sustains human dendritic cell precursors with T cell regulatory activity and capacity to differentiate into functional dendritic cells. Immunol Lett 2008; 116 (01) 41-54
- 95 Gregori S, Tomasoni D, Pacciani V. , et al. Differentiation of type 1 T regulatory cells (Tr1) by tolerogenic DC-10 requires the IL-10-dependent ILT4/HLA-G pathway. Blood 2010; 116 (06) 935-944
- 96 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
- 97 Correale P, Campoccia G, Tsang KY. , et al. Recruitment of dendritic cells and enhanced antigen-specific immune reactivity in cancer patients treated with hr-GM-CSF (Molgramostim) and hr-IL-2. results from a phase Ib clinical trial. Eur J Cancer 2001; 37 (07) 892-902
- 98 Redman BG, Chang AE, Whitfield J. , et al. Phase Ib trial assessing autologous, tumor-pulsed dendritic cells as a vaccine administered with or without IL-2 in patients with metastatic melanoma. J Immunother 2008; 31 (06) 591-598
- 99 Dhodapkar MV, Steinman RM, Krasovsky J, Munz C, Bhardwaj N. Antigen-specific inhibition of effector T cell function in humans after injection of immature dendritic cells. J Exp Med 2001; 193 (02) 233-238
- 100 Dhodapkar MV, Steinman RM. Antigen-bearing immature dendritic cells induce peptide-specific CD8(+) regulatory T cells in vivo in humans. Blood 2002; 100 (01) 174-177
- 101 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 (09) 2026-2032
- 102 Hilkens CM, Isaacs JD, Thomson AW. Development of dendritic cell-based immunotherapy for autoimmunity. Int Rev Immunol 2010; 29 (02) 156-183
- 103 Harry RA, Anderson AE, Isaacs JD, Hilkens CM. Generation and characterisation of therapeutic tolerogenic dendritic cells for rheumatoid arthritis. Ann Rheum Dis 2010; 69 (11) 2042-2050
- 104 Raϊch-Regué D, Grau-López L, Naranjo-Gómez M. , et al. Stable antigen-specific T-cell hyporesponsiveness induced by tolerogenic dendritic cells from multiple sclerosis patients. Eur J Immunol 2012; 42 (03) 771-782
- 105 Barrett AJ, Rezvani K, Solomon S. , et al. New developments in allotransplant immunology. Hematology (Am Soc Hematol Educ Program) 2003; 20 03: 350-371
- 106 Ravindra KV, Wu S, McKinney M, Xu H, Ildstad ST. Composite tissue allotransplantation: current challenges. Transplant Proc 2009; 41 (09) 3519-3528