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Pediatric Nephrology
Erschienen in:

12.03.2021 | Review

Biomarkers of immune tolerance in kidney transplantation: an overview

verfasst von: Wee-Song Yeo, Qin Xiang Ng

Erschienen in: Pediatric Nephrology | Ausgabe 3/2022

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Abstract

Kidney failure, one of the most prevalent diseases in the world and with increasing incidence, is associated with substantial morbidity and mortality. Currently available modes of kidney replacement therapy include dialysis and kidney transplantation. Though kidney transplantation is the preferred and ideal mode of kidney replacement therapy, this modality, however, is not without its risks. Kidney transplant recipients are constantly at risk of complications associated with immunosuppression, namely, opportunistic infections (e.g., Epstein-Barr virus and cytomegalovirus infections), post-transplant lymphoproliferative disorder, and complications associated with immunosuppressants (e.g., calcineurin inhibitor- and corticosteroid-associated new onset diabetes after transplantation and calcineurin inhibitor-associated nephrotoxicity). Transplantation tolerance, an acquired state in which immunocompetent recipients have developed donor-specific unresponsiveness, may be the Holy Grail in enabling optimal allograft survival and obviating the risks associated with immunosuppression in kidney transplant recipients. This review aims to discuss the biomarkers available to predict, identify, and define the transplant immune tolerant state and various tolerance induction strategies. Regrettably, pediatric patients have not been included in any tolerance studies and this should be the focus of future studies.
Literatur
1.
Smith JM, Dharnidharka VR (2015) Viral surveillance and subclinical viral infection in pediatric kidney transplantation. Pediatr Nephrol 30:741–748PubMedCrossRef
2.
Mynarek M, Hussein K, Kreipe HH, Maecker-Kolhoff B (2014) Malignancies after pediatric kidney transplantation: more than PTLD? Pediatr Nephrol 29:1517–1528PubMedCrossRef
3.
Naesens M, Kuypers DR, Sarwal M (2009) Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 4:481–508PubMedCrossRef
4.
Lakkis FG (2003) Transplantation tolerance: a journey from ignorance to memory. Nephrol Dial Transplant 18:1979–1982PubMedCrossRef
5.
Shapiro R, Sarwal MM (2010) Pediatric kidney transplantation. Pediatr Clin N Am 57:393–400CrossRef
6.
Georgel P (2016) Innate immune receptors in solid organ transplantation. Hum Immunol 77:1071–1075PubMedCrossRef
7.
8.
Lakkis FG, Li XC (2018) Innate allorecognition by monocytic cells and its role in graft rejection. Am J Transplant 18:289–292PubMedCrossRef
9.
10.
Mannam VK, Lewis RE, Cruse JM (2013) The fate of renal allografts hinges on responses of the microvascular endothelium. Exp Mol Pathol 94:398–411PubMedCrossRef
11.
Chen CC, Koenig A, Saison C, Dahdal S, Rigault G, Barba T, Taillardet M, Chartoire D, Ovize M, Morelon E, Defrance T, Thaunat O (2018) CD4+ T cell help is mandatory for naive and memory donor-specific antibody responses: impact of therapeutic immunosuppression. Front Immunol 9:275PubMedPubMedCentralCrossRef
12.
Gershon RK, Cohen P, Hencin R, Liebhaber SA (1972) Suppressor T cells. J Immunol 108:586–590PubMedCrossRef
13.
14.
Gershon RK, Kondo K (1970) Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology 18:723–737PubMedPubMedCentral
15.
Sakaguchi S, Sakaguchi N, Asano M, Itoh M, Toda M (1995) 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 155:1151–1164PubMedCrossRef
16.
Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061PubMedCrossRef
17.
Marek-Trzonkowska N, Mysliwiec M, Dobyszuk A, Grabowska M, Techmanska I, Juscinska J, Wujtewicz MA, Witkowski P, Mlynarski W, Balcerska A, Mysliwska J, Trzonkowski P (2012) Administration of CD4+CD25highCD127- regulatory T cells preserves β-cell function in type 1 diabetes in children. Diabetes Care 35:1817–1820PubMedPubMedCentralCrossRef
18.
Juvet SC, Whatcott AG, Bushell AR, Wood KJ (2014) Harnessing regulatory T cells for clinical use in transplantation: the end of the beginning. Am J Transplant 14:750–763PubMedCrossRef
19.
Tang Q, Bluestone JA, Kang SM (2012) CD4(+)Foxp3(+) regulatory T cell therapy in transplantation. J Mol Cell Biol 4:11–21PubMedCrossRef
20.
Evans JG, Chavez-Rueda KA, Eddaoudi A, Meyer-Bahlburg A, Rawlings DJ, Ehrenstein MR, Mauri C (2007) Novel suppressive function of transitional 2 B cells in experimental arthritis. J Immunol 178:7868–7878PubMedCrossRef
21.
22.
Schioppa T, Moore R, Thompson RG, Rosser EC, Kulbe H, Nedospasov S, Mauri C, Coussens LM, Balkwill FR (2011) B regulatory cells and the tumor-promoting actions of TNF-α during squamous carcinogenesis. Proc Natl Acad Sci U S A 108:10662–10667PubMedPubMedCentralCrossRef
23.
Ding Q, Yeung M, Camirand G, Zeng Q, Akiba H, Yagita H, Chalasani G, Sayegh MH, Najafian N, Rothstein DM (2011) 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 121:3645–3656PubMedPubMedCentralCrossRef
24.
Rosser EC, Mauri C (2015) Regulatory B cells: origin, phenotype, and function. Immunity 42:607–612PubMedCrossRef
25.
Tedder TF (2015) B10 cells: a functionally defined regulatory B cell subset. J Immunol 194:1395–1401PubMedCrossRef
26.
Clatworthy MR, Watson CJ, Plotnek G, Bardsley V, Chaudhry AN, Bradley JA, Smith KG (2009) B cell-depleting induction therapy and acute cellular rejection. N Engl J Med 360:2683–2685PubMedPubMedCentralCrossRef
27.
Tebbe B, Wilde B, Ye Z, Wang J, Wang X, Jian F, Dolff S, Schedlowski M, Hoyer PF, Kribben A, Witzke O, Hoerning A (2016) Renal transplant recipients treated with calcineurin-inhibitors lack circulating immature transitional CD19+CD24hiCD38hi regulatory B-lymphocytes. PLoS One 11:e0153170PubMedPubMedCentralCrossRef
28.
Flores-Borja F, Bosma A, Ng D, Reddy V, Ehrenstein MR, Isenberg DA, Mauri C (2013) CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci Transl Med 5:173ra23
29.
Mellman I (2013) Dendritic cells: master regulators of the immune response. Cancer Immunol Res 1:145–149PubMedCrossRef
30.
Liu YJ (2001) Dendritic cell subsets and lineages, and their functions in innate and adaptive immunity. Cell 106:259–262PubMedCrossRef
31.
Steinman RM, Hawiger D, Liu K, Bonifaz L, Bonnyay D, Mahnke K, Iyoda T, Ravetch J, Dhodapkar M, Inaba K, Nussenzweig M (2003) Dendritic cell function in vivo during the steady state: a role in peripheral tolerance. Ann N Y Acad Sci 987:15–25PubMedCrossRef
32.
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop DJ, Horwitz E (2006) Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 8:315–317
33.
Casiraghi F, Perico N, Cortinovis M, Remuzzi G (2016) Mesenchymal stromal cells in renal transplantation: opportunities and challenges. Nat Rev Nephrol 12:241–253PubMedCrossRef
34.
Ge W, Jiang J, Arp J, Liu W, Garcia B, Wang H (2010) Regulatory T cell generation and kidney allograft tolerance induced by mesenchymal stem cells associated with indoleamine 2,3-dioxygenase expression. Transplantation 90:1312–1320PubMedCrossRef
35.
He Y, Zhou S, Liu H, Shen B, Zhao H, Peng K, Wu X (2015) Indoleamine 2, 3-dioxgenase transfected mesenchymal stem cells induce kidney allograft tolerance by increasing the production and function of regulatory T cells. Transplantation 99:1829–1838PubMedCrossRef
36.
Massart A, Pallier A, Pascual J, Viklicky O, Budde K, Spasovski G, Klinger M, Sever MS, Sørensen SS, Hadaya K, Oberbauer R, Dudley C, De Fijter JW, Yussim A, Hazzan M, Wekerle T, Berglund D, De Biase C, Pérez-Sáez MJ, Mühlfeld A, Orlando G, Clemente K, Lai Q, Pisani F, Kandus A, Baas M, Bemelman F, Ponikvar JB, Mazouz H, Stratta P, Subra JF, Villemain F, Hoitsma A, Braun L, Cantarell MC, Colak H, Courtney A, Frasca GM, Howse M, Naesens M, Reischig T, Serón D, Seyahi N, Tugmen C, Alonso Hernandez A, Beňa L, Biancone L, Cuna V, Díaz-Corte C, Dufay A, Gaasbeek A, Garnier A, Gatault P, Gentil Govantes MA, Glowacki F, Gross O, Hurault de Ligny B, Huynh-Do U, Janbon B, Jiménez Del Cerro LA, Keller F, La Manna G, Lauzurica R, Le Monies De Sagazan H, Thaiss F, Legendre C, Martin S, Moal MC, Noël C, Pillebout E, Piredda GB, Puga AR, Sulowicz W, Tuglular S, Prokopova M, Chesneau M, Le Moine A, Guérif P, Soulillou JP, Abramowicz M, Giral M, Racapé J, Maggiore U, Brouard S, Abramowicz D (2016) The DESCARTES-Nantes survey of kidney transplant recipients displaying clinical operational tolerance identifies 35 new tolerant patients and 34 almost tolerant patients. Nephrol Dial Transplant 31:1002–1013PubMedCrossRef
37.
Brouard S, Pallier A, Renaudin K, Foucher Y, Danger R, Devys A, Cesbron A, Guillot-Guegen C, Ashton-Chess J, Le Roux S, Harb J, Roussey G, Subra JF, Villemain F, Legendre C, Bemelman FJ, Orlando G, Garnier A, Jambon H, Le Monies De Sagazan H, Braun L, Noël C, Pillebout E, Moal MC, Cantarell C, Hoitsma A, Ranbant M, Testa A, Soulillou JP, Giral M (2012) The natural history of clinical operational tolerance after kidney transplantation through twenty-seven cases. Am J Transplant 12:3296–3307PubMedCrossRef
38.
Sagoo P, Perucha E, Sawitzki B, Tomiuk S, Stephens DA, Miqueu P, Chapman S, Craciun L, Sergeant R, Brouard S, Rovis F, Jimenez E, Ballow A, Giral M, Rebollo-Mesa I, Le Moine A, Braudeau C, Hilton R, Gerstmayer B, Bourcier K, Sharif A, Krajewska M, Lord GM, Roberts I, Goldman M, Wood KJ, Newell K, Seyfert-Margolis V, Warrens AN, Janssen U, Volk HD, Soulillou JP, Hernandez-Fuentes MP, Lechler RI (2010) Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans. J Clin Invest 120:1848–1861PubMedPubMedCentralCrossRef
39.
Newell KA, Asare A, Kirk AD, Gisler TD, Bourcier K, Suthanthiran M, Burlingham WJ, Marks WH, Sanz I, Lechler RI, Hernandez-Fuentes MP, Turka LA, Seyfert-Margolis VL; Immune Tolerance Network ST507 Study Group (2010) Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest 120:1836–1847CrossRef
40.
Newell KA, Asare A, Sanz I, Wei C, Rosenberg A, Gao Z, Kanaparthi S, Asare S, Lim N, Stahly M, Howell M, Knechtle S, Kirk A, Marks WH, Kawai T, Spitzer T, Tolkoff-Rubin N, Sykes M, Sachs DH, Cosimi AB, Burlingham WJ, Phippard D, Turka LA (2015) Longitudinal studies of a B cell-derived signature of tolerance in renal transplant recipients. Am J Transplant 15:2908–2920PubMedPubMedCentralCrossRef
41.
Roedder S, Li L, Alonso MN, Hsieh SC, Vu MT, Dai H, Sigdel TK, Bostock I, Macedo C, Metes D, Zeevi A, Shapiro R, Salvatierra O, Scandling J, Alberu J, Engleman E, Sarwal MM (2015) A three-gene assay for monitoring immune quiescence in kidney transplantation. J Am Soc Nephrol 26:2042–2053PubMedCrossRef
42.
Brouard S, Mansfield E, Braud C, Li L, Giral M, Hsieh SC, Baeten D, Zhang M, Ashton-Chess J, Braudeau C, Hsieh F, Dupont A, Pallier A, Moreau A, Louis S, Ruiz C, Salvatierra O, Soulillou JP, Sarwal M (2007) Identification of a peripheral blood transcriptional biomarker panel associated with operational renal allograft tolerance. Proc Natl Acad Sci U S A 104:15448–15453PubMedPubMedCentralCrossRef
43.
Roussey-Kesler G, Giral M, Moreau A, Subra JF, Legendre C, Noël C, Pillebout E, Brouard S, Soulillou JP (2006) Clinical operational tolerance after kidney transplantation. Am J Transplant 6:736–746PubMedCrossRef
44.
Braud C, Baeten D, Giral M, Pallier A, Ashton-Chess J, Braudeau C, Chevalier C, Lebars A, Léger J, Moreau A, Pechkova E, Nicolini C, Soulillou JP, Brouard S (2008) Immunosuppressive drug-free operational immune tolerance in human kidney transplant recipients: Part I. Blood gene expression statistical analysis. J Cell Biochem 103:1681–1692PubMedCrossRef
45.
Chong AS, Sciammas R (2011) Matchmaking the B cell signature of tolerance to regulatory B cells. Am J Transplant 11:2555–2560PubMedCrossRef
46.
Newell KA, Adams AB, Turka LA (2018) Biomarkers of operational tolerance following kidney transplantation - the immune tolerance network studies of spontaneously tolerant kidney transplant recipients. Hum Immunol 79:380–387PubMedPubMedCentralCrossRef
47.
Louis S, Braudeau C, Giral M, Dupont A, Moizant F, Robillard N, Moreau A, Soulillou JP, Brouard S (2006) Contrasting CD25hiCD4+T cells/FOXP3 patterns in chronic rejection and operational drug-free tolerance. Transplantation 81:398–407PubMedCrossRef
48.
Baeten D, Louis S, Braud C, Braudeau C, Ballet C, Moizant F, Pallier A, Giral M, Brouard S, Soulillou JP (2006) Phenotypically and functionally distinct CD8+ lymphocyte populations in long-term drug-free tolerance and chronic rejection in human kidney graft recipients. J Am Soc Nephrol 17:294–304PubMedCrossRef
49.
Moraes-Vieira PM, Silva HM, Takenaka MC, Monteiro SM, Lemos F, Saitovitch D, Kalil J, Coelho V (2010) Differential monocyte STAT6 activation and CD4(+)CD25(+)Foxp3(+) T cells in kidney operational tolerance transplanted individuals. Hum Immunol 71:442–450PubMedCrossRef
50.
Braza F, Dugast E, Panov I, Paul C, Vogt K, Pallier A, Chesneau M, Baron D, Guerif P, Lei H, Laplaud DA, Volk HD, Degauque N, Giral M, Soulillou JP, Sawitzki B, Brouard S (2015) Central role of CD45RA- Foxp3hi memory regulatory T cells in clinical kidney transplantation tolerance. J Am Soc Nephrol 26:1795–1805PubMedPubMedCentralCrossRef
51.
Haynes LD, Jankowska-Gan E, Sheka A, Keller MR, Hernandez-Fuentes MP, Lechler RI, Seyfert-Margolis V, Turka LA, Newell KA, Burlingham WJ (2012) Donor-specific indirect pathway analysis reveals a B cell-independent signature which reflects outcomes in kidney transplant recipients. Am J Transplant 12:640–648PubMedCrossRef
52.
Chesneau M, Pallier A, Braza F, Lacombe G, Le Gallou S, Baron D, Giral M, Danger R, Guerif P, Aubert-Wastiaux H, Néel A, Michel L, Laplaud DA, Degauque N, Soulillou JP, Tarte K, Brouard S (2014) Unique B cell differentiation profile in tolerant kidney transplant patients. Am J Transplant 14:144–155PubMedCrossRef
53.
Deng S, Moore DJ, Huang X, Lian MM, Mohiuddin M, Velededeoglu E, Lee MK 4th, Sonawane S, Kim J, Wang J, Chen H, Corfe SA, Paige C, Shlomchik M, Caton A, Markmann JF (2007) Cutting edge: transplant tolerance induced by anti-CD45RB requires B lymphocytes. J Immunol 178:6028–6032PubMedCrossRef
54.
Le Texier L, Thebault P, Lavault A, Usal C, Merieau E, Quillard T, Charreau B, Soulillou JP, Cuturi MC, Brouard S, Chiffoleau E (2011) Long-term allograft tolerance is characterized by the accumulation of B cells exhibiting an inhibited profile. Am J Transplant 11:429–438PubMedCrossRef
55.
Stolp J, Turka LA, Wood KJ (2014) B cells with immune-regulating function in transplantation. Nat Rev Nephrol 10:389–397PubMedCrossRef
56.
Pallier A, Hillion S, Danger R, Giral M, Racapé M, Degauque N, Dugast E, Ashton-Chess J, Pettré S, Lozano JJ, Bataille R, Devys A, Cesbron-Gautier A, Braudeau C, Larrose C, Soulillou JP, Brouard S (2010) Patients with drug-free long-term graft function display increased numbers of peripheral B cells with a memory and inhibitory phenotype. Kidney Int 78:503–513PubMedCrossRef
57.
Silva HM, Takenaka MC, Moraes-Vieira PM, Monteiro SM, Hernandez MO, Chaara W, Six A, Agena F, Sesterheim P, Barbé-Tuana FM, Saitovitch D, Lemos F, Kalil J, Coelho V (2012) Preserving the B cell compartment favors operational tolerance in human renal transplantation. Mol Med 18:733–743PubMedPubMedCentralCrossRef
58.
Nova-Lamperti E, Fanelli G, Becker PD, Chana P, Elgueta R, Dodd PC, Lord GM, Lombardi G, Hernandez-Fuentes MP (2016) IL-10-produced by human transitional B-cells down-regulates CD86 expression on B-cells leading to inhibition of CD4+T cell responses. Sci Rep 6:20044PubMedPubMedCentralCrossRef
59.
Chesneau M, Michel L, Dugast E, Chenouard A, Baron D, Pallier A, Durand J, Braza F, Guerif P, Laplaud DA, Soulillou JP, Giral M, Degauque N, Chiffoleau E, Brouard S (2015) Tolerant kidney transplant patients produce b cells with regulatory properties. J Am Soc Nephrol 26:2588–2598PubMedPubMedCentralCrossRef
60.
Hutchinson JA, Riquelme P, Sawitzki B, Tomiuk S, Miqueu P, Zuhayra M, Oberg HH, Pascher A, Lützen U, Janssen U, Broichhausen C, Renders L, Thaiss F, Scheuermann E, Henze E, Volk HD, Chatenoud L, Lechler RI, Wood KJ, Kabelitz D, Schlitt HJ, Geissler EK, Fändrich F (2011) Cutting edge: immunological consequences and trafficking of human regulatory macrophages administered to renal transplant recipients. J Immunol 187:2072–2078PubMedCrossRef
61.
Xia G, He J, Leventhal JR (2008) Ex vivo-expanded natural CD4+CD25+ regulatory T cells synergize with host T cell depletion to promote long-term survival of allografts. Am J Transplant 8:298–306PubMedCrossRef
62.
Putnam AL, Safinia N, Medvec A, Laszkowska M, Wray M, Mintz MA, Trotta E, Szot GL, Liu W, Lares A, Lee K, Laing A, Lechler RI, Riley JL, Bluestone JA, Lombardi G, Tang Q (2013) Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for use in transplantation. Am J Transplant 13:3010–3020PubMedPubMedCentralCrossRef
63.
Owen RD (1945) immunogenetic consequences of vascular anastomoses between bovine twins. Science 102:400–401PubMedCrossRef
64.
Sharabi Y, Sachs DH (1989) Mixed chimerism and permanent specific transplantation tolerance induced by a nonlethal preparative regimen. J Exp Med 169:493–502PubMedCrossRef
65.
Fuchimoto Y, Huang CA, Yamada K, Shimizu A, Kitamura H, Colvin RB, Ferrara V, Murphy MC, Sykes M, White-Scharf M, Neville DM Jr, Sachs DH (2000) Mixed chimerism and tolerance without whole body irradiation in a large animal model. J Clin Invest 105:1779–1789PubMedPubMedCentralCrossRef
66.
Kawai T, Cosimi AB, Colvin RB, Powelson J, Eason J, Kozlowski T, Sykes M, Monroy R, Tanaka M, Sachs DH (1995) Mixed allogeneic chimerism and renal allograft tolerance in cynomolgus monkeys. Transplantation 59:256–262PubMedCrossRef
67.
Kimikawa M, Sachs DH, Colvin RB, Bartholomew A, Kawai T, Cosimi AB (1997) Modifications of the conditioning regimen for achieving mixed chimerism and donor-specific tolerance in cynomolgus monkeys. Transplantation 64:709–716PubMedCrossRef
68.
Kawai T, Poncelet A, Sachs DH, Mauiyyedi S, Boskovic S, Wee SL, Ko DS, Bartholomew A, Kimikawa M, Hong HZ, Abrahamian G, Colvin RB, Cosimi AB (1999) Long-term outcome and alloantibody production in a non-myeloablative regimen for induction of renal allograft tolerance. Transplantation 68:1767–1775PubMedCrossRef
69.
Kawai T, Sogawa H, Boskovic S, Abrahamian G, Smith RN, Wee SL, Andrews D, Nadazdin O, Koyama I, Sykes M, Winn HJ, Colvin RB, Sachs DH, Cosimi AB (2004) CD154 blockade for induction of mixed chimerism and prolonged renal allograft survival in nonhuman primates. Am J Transplant 4:1391–1398PubMedCrossRef
70.
Kawai T, Cosimi AB, Spitzer TR, Tolkoff-Rubin N, Suthanthiran M, Saidman SL, Shaffer J, Preffer FI, Ding R, Sharma V, Fishman JA, Dey B, Ko DS, Hertl M, Goes NB, Wong W, Williams WW Jr, Colvin RB, Sykes M, Sachs DH (2008) HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 358:353–361PubMedPubMedCentralCrossRef
71.
Kawai T, Sachs DH, Sykes M, Cosimi AB, Network IT (2013) HLA-mismatched renal transplantation without maintenance immunosuppression. N Engl J Med 368(19):1850–1852PubMedPubMedCentralCrossRef
72.
Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Millan MT, Shizuru JA, Hoppe RT, Lowsky R, Engleman EG, Strober S (2008) Tolerance and chimerism after renal and hematopoietic-cell transplantation. N Engl J Med 358:362–368PubMedCrossRef
73.
Scandling JD, Busque S, Shizuru JA, Engleman EG, Strober S (2011) Induced immune tolerance for kidney transplantation. N Engl J Med 365:1359–1360PubMedPubMedCentralCrossRef
74.
Scandling JD, Busque S, Dejbakhsh-Jones S, Benike C, Sarwal M, Millan MT, Shizuru JA, Lowsky R, Engleman EG, Strober S (2012) Tolerance and withdrawal of immunosuppressive drugs in patients given kidney and hematopoietic cell transplants. Am J Transplant 12:1133–1145PubMedPubMedCentralCrossRef
75.
Scandling JD, Busque S, Shizuru JA, Lowsky R, Hoppe R, Dejbakhsh-Jones S, Jensen K, Shori A, Strober JA, Lavori P, Turnbull BB, Engleman EG, Strober S (2015) Chimerism, graft survival, and withdrawal of immunosuppressive drugs in HLA matched and mismatched patients after living donor kidney and hematopoietic cell transplantation. Am J Transplant 15:695–704PubMedCrossRef
76.
Busque S, Scandling JD, Lowsky R, Shizuru J, Jensen K, Waters J, Wu HH, Sheehan K, Shori A, Choi O, Pham T, Fernandez Vina MA, Hoppe R, Tamaresis J, Lavori P, Engleman EG, Meyer E, Strober S (2020) Mixed chimerism and acceptance of kidney transplants after immunosuppressive drug withdrawal. Sci Transl Med 12:eaax8863
77.
Leventhal J, Abecassis M, Miller J, Gallon L, Tollerud D, Elliott MJ, Bozulic LD, Houston C, Sustento-Reodica N, Ildstad ST (2013) Tolerance induction in HLA disparate living donor kidney transplantation by donor stem cell infusion: durable chimerism predicts outcome. Transplantation 95:169–176PubMedPubMedCentralCrossRef
78.
Leventhal JR, Mathew JM, Salomon DR, Kurian SM, Friedewald JJ, Gallon L, Konieczna I, Tambur AR, Charette J, Levitsky J, Jie C, Kanwar YS, Abecassis MM, Miller J (2016) Nonchimeric HLA-identical renal transplant tolerance: regulatory immunophenotypic/genomic biomarkers. Am J Transplant 16:221–234PubMedCrossRef
79.
80.
Kawai T, Cosimi AB, Wee SL, Houser S, Andrews D, Sogawa H, Phelan J, Boskovic S, Nadazdin O, Abrahamian G, Colvin RB, Sach DH, Madsen JC (2002) Effect of mixed hematopoietic chimerism on cardiac allograft survival in cynomolgus monkeys. Transplantation 73:1757–1764PubMedCrossRef
81.
Bartholomew A, Polchert D, Szilagyi E, Douglas GW, Kenyon N (2009) Mesenchymal stem cells in the induction of transplantation tolerance. Transplantation 87:S55–S57PubMedCrossRef
82.
83.
Mattar P, Bieback K (2015) Comparing the immunomodulatory properties of bone marrow, adipose tissue, and birth-associated tissue mesenchymal stromal cells. Front Immunol 6:560PubMedPubMedCentralCrossRef
84.
Naji A, Eitoku M, Favier B, Deschaseaux F, Rouas-Freiss N, Suganuma N (2019) Biological functions of mesenchymal stem cells and clinical implications. Cell Mol Life Sci 76:3323–3348PubMedCrossRef
85.
86.
Ge W, Jiang J, Baroja ML, Arp J, Zassoko R, Liu W, Bartholomew A, Garcia B, Wang H (2009) Infusion of mesenchymal stem cells and rapamycin synergize to attenuate alloimmune responses and promote cardiac allograft tolerance. Am J Transplant 9:1760–1772PubMedCrossRef
87.
Larocca RA, Moraes-Vieira PM, Bassi EJ, Semedo P, de Almeida DC, da Silva MB, Thornley T, Pacheco-Silva A, Câmara NO (2013) Adipose tissue-derived mesenchymal stem cells increase skin allograft survival and inhibit Th-17 immune response. PLoS One 8:e76396PubMedPubMedCentralCrossRef
88.
Ma T, Wang X, Jiao Y, Wang H, Qi Y, Gong H, Zhang L, Jiang D (2018) Interleukin 17 (IL-17)-induced mesenchymal stem cells prolong the survival of allogeneic skin grafts. Ann Transplant 23:615–621PubMedPubMedCentralCrossRef
89.
Gao W, Zhang L, Zhang Y, Sun C, Chen X, Wang Y (2017) Adipose-derived mesenchymal stem cells promote liver regeneration and suppress rejection in small-for-size liver allograft. Transpl Immunol 45:1–7PubMedCrossRef
90.
Despeyroux A, Duret C, Gondeau C, Perez-Gracia E, Chuttoo L, de Boussac H, Briolotti P, Bony C, Noël D, Jorgensen C, Larrey D, Daujat-Chavanieu M, Herrero A (2018) Mesenchymal stem cells seeded on a human amniotic membrane improve liver regeneration and mouse survival after extended hepatectomy. J Tissue Eng Regen Med 12:1062–1073PubMedCrossRef
91.
Yu P, Wang Z, Liu Y, Xiao Z, Guo Y, Li M, Zhao M (2017) Marrow mesenchymal stem cells effectively reduce histologic changes in a rat model of chronic renal allograft rejection. Transplant Proc 49:2194–2203PubMedCrossRef
92.
Tan J, Wu W, Xu X, Liao L, Zheng F, Messinger S, Sun X, Chen J, Yang S, Cai J, Gao X, Pileggi A, Ricordi C (2012) Induction therapy with autologous mesenchymal stem cells in living-related kidney transplants: a randomized controlled trial. JAMA 307:1169–1177PubMedCrossRef
93.
Peng Y, Ke M, Xu L, Liu L, Chen X, Xia W, Li X, Chen Z, Ma J, Liao D, Li G, Fang J, Pan G, Xiang AP (2013) Donor-derived mesenchymal stem cells combined with low-dose tacrolimus prevent acute rejection after renal transplantation: a clinical pilot study. Transplantation 95:161–168PubMedCrossRef
94.
Pan GH, Chen Z, Xu L, Zhu JH, Xiang P, Ma JJ, Peng YW, Li GH, Chen XY, Fang JL, Guo YH, Zhang L, Liu LS (2016) Low-dose tacrolimus combined with donor-derived mesenchymal stem cells after renal transplantation: a prospective, non-randomized study. Oncotarget 7:12089–12101PubMedPubMedCentralCrossRef
95.
Mudrabettu C, Kumar V, Rakha A, Yadav AK, Ramachandran R, Kanwar DB, Nada R, Minz M, Sakhuja V, Marwaha N, Jha V (2015) Safety and efficacy of autologous mesenchymal stromal cells transplantation in patients undergoing living donor kidney transplantation: a pilot study. Nephrology (Carlton) 20:25–33CrossRef
96.
Sun Q, Huang Z, Han F, Zhao M, Cao R, Zhao D, Hong L, Na N, Li H, Miao B, Hu J, Meng F, Peng Y, Sun Q (2018) Allogeneic mesenchymal stem cells as induction therapy are safe and feasible in renal allografts: pilot results of a multicenter randomized controlled trial. J Transl Med 16:52PubMedPubMedCentralCrossRef
97.
Erpicum P, Weekers L, Detry O, Bonvoisin C, Delbouille MH, Grégoire C, Baudoux E, Briquet A, Lechanteur C, Maggipinto G, Somja J, Pottel H, Baron F, Jouret F, Beguin Y (2019) Infusion of third-party mesenchymal stromal cells after kidney transplantation: a phase I-II, open-label, clinical study. Kidney Int 95:693–707PubMedCrossRef
98.
Safinia N, Scotta C, Vaikunthanathan T, Lechler RI, Lombardi G (2015) Regulatory T cells: serious contenders in the promise for immunological tolerance in transplantation. Front Immunol 6:438PubMedPubMedCentralCrossRef
99.
Fu S, Zhang N, Yopp AC, Chen D, Mao M, Chen D, Zhang H, Ding Y, Bromberg JS (2004) TGF-beta induces Foxp3 + T-regulatory cells from CD4 + CD25 - precursors. Am J Transplant 4:1614–1627PubMedCrossRef
100.
Golshayan D, Jiang S, Tsang J, Garin MI, Mottet C, Lechler RI (2007) In vitro-expanded donor alloantigen-specific CD4+CD25+ regulatory T cells promote experimental transplantation tolerance. Blood 109:827–835PubMedCrossRef
101.
Ge W, Jiang J, Liu W, Lian D, Saito A, Garcia B, Li XC, Wang H (2010) Regulatory T cells are critical to tolerance induction in presensitized mouse transplant recipients through targeting memory T cells. Am J Transplant 10:1760–1773PubMedCrossRef
102.
Chandran S, Tang Q, Sarwal M, Laszik ZG, Putnam AL, Lee K, Leung J, Nguyen V, Sigdel T, Tavares EC, Yang JYC, Hellerstein M, Fitch M, Bluestone JA, Vincenti F (2017) Polyclonal regulatory T cell therapy for control of inflammation in kidney transplants. Am J Transplant 17:2945–2954PubMedPubMedCentralCrossRef
103.
Mathew JM, Jessica H, LeFever A, Konieczna I, Stratton C, He J, Huang X, Gallon L, Skaro A, Ansari MJ, Leventhal JR (2018) A phase I clinical trial with ex vivo expanded recipient regulatory T cells in living donor kidney transplants. Sci Rep 8:7428PubMedPubMedCentralCrossRef
104.
Todo S, Yamashita K, Goto R, Zaitsu M, Nagatsu A, Oura T, Watanabe M, Aoyagi T, Suzuki T, Shimamura T, Kamiyama T (2016) A pilot study of operational tolerance with a regulatory T cell-based cell therapy in living donor liver transplantation. Hepatology 64:632–643PubMedCrossRef
105.
Sánchez-Fueyo A, Whitehouse G, Grageda N, Cramp ME, Lim TY, Romano M, Thirkell S, Lowe K, Fry L, Heward J, Kerr A (2020) Applicability, safety, and biological activity of regulatory T cell therapy in liver transplantation. Am J Transplant 20:1125–1136PubMedPubMedCentralCrossRef
106.
Zhang Q, Lu W, Liang CL, Chen Y, Liu H, Qiu F, Dai Z (2018) Chimeric antigen receptor (CAR) Treg: A promising approach to inducing immunological tolerance. Front Immunol 9:2359PubMedPubMedCentralCrossRef
107.
Verneris MR, Lee SJ, Ahn KW, Wang HL, Battiwalla M, Inamoto Y, Fernandez-Vina MA, Gajewski J, Pidala J, Munker R, Aljurf M, Saber W, Spellman S, Koreth J (2015) HLA mismatch is associated with worse outcomes after unrelated donor reduced-intensity conditioning hematopoietic cell transplantation: an analysis from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant 21:1783–1789PubMedPubMedCentralCrossRef
108.
González-Galarza FF, Takeshita LY, Santos EJ, Kempson F, Maia MH, Silva AL, Silva AL, Ghattaoraya GS, Alfirevic A, Jones AR, Middleton D (2015) Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res 43:D784–D788PubMedCrossRef
109.
Burt C, Cryer C, Fuggle S, Little AM, Dyer P (2013) HLA-A,-B,-DR allele group frequencies in 7007 kidney transplant list patients in 27 UK centres. Int J Immunogenet 40:209–215PubMedCrossRef
110.
Boardman DA, Philippeos C, Fruhwirth GO, Ibrahim MA, Hannen RF, Cooper D, Marelli-Berg FM, Watt FM, Lechler RI, Maher J, Smyth LA, Lombardi G (2017) Expression of a chimeric antigen receptor specific for donor HLA class I enhances the potency of human regulatory T cells in preventing human skin transplant rejection. Am J Transplant 17:931–943PubMedCrossRef
111.
Noyan F, Zimmermann K, Hardtke-Wolenski M, Knoefel A, Schulde E, Geffers R (2017) Prevention of allograft rejection by use of regulatory T cells with an MHC-specific chimeric antigen receptor. Am J Transplant 17:917–930PubMedCrossRef
112.
Weber SE, Harbertson J, Godebu E, Mros GA, Padrick RC, Carson BD (2006) Adaptive islet-specific regulatory CD4 T cells control autoimmune diabetes and mediate the disappearance of pathogenic Th1 cells in vivo. J Immunol 176:4730–4739PubMedCrossRef
113.
Hutchinson JA, Riquelme P, Brem-Exner BG, Schulze M, Matthäi M, Renders L, Kunzendorf U, Geissler EK, Fändrich F (2008) Transplant acceptance-inducing cells as an immune-conditioning therapy in renal transplantation. Transpl Int 21:728–741PubMedCrossRef
114.
Hutchinson JA, Brem-Exner BG, Riquelme P, Roelen D, Schulze M, Ivens K, Grabensee B, Witzke O, Philipp T, Renders L, Humpe A (2008) A cell-based approach to the minimization of immunosuppression in renal transplantation. Transpl Int 21:742–754PubMedCrossRef
115.
Geissler EK (2012) The ONE Study compares cell therapy products in organ transplantation: introduction to a review series on suppressive monocyte-derived cells. Transplant Res 1:11
116.
Riquelme P, Geissler EK, Hutchinson JA (2012) Alternative approaches to myeloid suppressor cell therapy in transplantation: comparing regulatory macrophages to tolerogenic DCs and MDSCs. Transplant Res 1:17
117.
Safinia N, Grageda N, Scottà C, Thirkell S, Fry LJ, Vaikunthanathan T, Lechler RI, Lombardi G (2018) Cell therapy in organ transplantation: our experience on the clinical translation of regulatory T cells. Front Immunol 9:354PubMedPubMedCentralCrossRef
118.
Ezzelarab MB, Zahorchak AF, Lu L, Morelli AE, Chalasani G, Demetris AJ, Lakkis FG, Wijkstrom M, Murase N, Humar A, Shapiro R (2013) Regulatory dendritic cell infusion prolongs kidney allograft survival in nonhuman primates. Am J Transplant 13:1989–2005PubMedPubMedCentralCrossRef
119.
Giannoukakis N, Phillips B, Finegold D, Harnaha J, Trucco M (2011) Phase I (safety) study of autologous tolerogenic dendritic cells in type 1 diabetic patients. Diabetes Care 34:2026–2032PubMedPubMedCentralCrossRef
120.
Metadaten
Titel
Biomarkers of immune tolerance in kidney transplantation: an overview
verfasst von
Wee-Song Yeo
Qin Xiang Ng
Publikationsdatum
12.03.2021
Verlag
Springer Berlin Heidelberg
Erschienen in
Pediatric Nephrology / Ausgabe 3/2022
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-021-05023-w

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