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The “Unusual Suspects” in Allograft Rejection: Will T Regulatory Cell Therapy Arrest Them?

  • Cellular Transplants (J Grinyó, Section Editor)
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Abstract

Several trials with adoptively transferred T regulatory cells (TRegs) have shown to be safe and—in some instances—to be effective in patients with hematological malignancies after allogeneic hematopoietic stem cell transplantation (to prevent graft-versus-host disease), with type 1 diabetes (to preserve residual beta cell function), and with refractory Crohn’s disease (to control the disease). In solid organ transplantation, TReg-cell therapy trials with TReg-supportive immunosuppression are currently being undertaken to control the well-documented T effector cells responsible for allograft rejection. Emerging reports show that many “unusual suspects” are involved in allograft rejection as well. Whether TReg-cell therapy will also target them remains to be investigated. In this review, we will shed some light on these underscored cells, the role TRegs would potentially have in controlling these unusual suspects, and the immune-monitoring strategies that would address potential TReg-cell therapy efficacy.

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References

Papers of particular interest have been highlighted as:• Of importance•• Of major importance

  1. Gershon RK, Kondo K. Cell interactions in the induction of tolerance: the role of thymic lymphocytes. Immunology. 1970;18:723–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. 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;155:1151–64.

    CAS  PubMed  Google Scholar 

  3. Groux H, O’Garra A, Bigler M, Rouleau M, Antonenko S, de Vries JE, et al. A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature. 1997;389:737–42.

    Article  CAS  PubMed  Google Scholar 

  4. Safinia N, Leech J, Hernandez-Fuentes M, Lechler R, Lombardi G. Promoting transplantation tolerance; adoptive regulatory T cell therapy. Clin Exp Immunol. 2013;172:158–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Roncarolo MG, Gregori S, Bacchetta R, Battaglia M. Tr1 cells and the counter-regulation of immunity: natural mechanisms and therapeutic applications. Curr Top Microbiol Immunol. 2014;380:39–68.

    CAS  PubMed  Google Scholar 

  6. Trzonkowski P, Bacchetta R, Battaglia M, Berglund D, Bohnenkamp HR, ten Brinke A, et al. Hurdles in therapy with regulatory T cells. Sci Transl Med. 2015;7:304ps18. This review describes performed and planned TReg cell trials and the corresponding challenges.

    Article  PubMed  Google Scholar 

  7. Landwehr-Kenzel S, Issa F, Luu SH, Schmück M, Lei H, Zobel A, et al. Novel GMP-compatible protocol employing an allogeneic B cell bank for clonal expansion of allospecific natural regulatory T cells. Am J Transplant. 2014;14:594–606.

    Article  CAS  PubMed  Google Scholar 

  8. Bacchetta R, Lucarelli B, Sartirana C, Gregori S, Lupo Stanghellini MT, Miqueu P, et al. Immunological outcome in haploidentical-HSC transplanted patients treated with IL-10-anergized donor T cells. Front Immunol. 2014;5:16. This paper describes the first Tr1-cell therapy study in humans with hematological malignancies.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Gregori S, Passerini L, Roncarolo MG. Clinical outlook for type-1 and FOXP3(+) T regulatory cell-based therapy. Front Immunol. 2015;6:593.

    PubMed  PubMed Central  Google Scholar 

  10. Marek-Trzonkowska N, Mysliwiec M, Dobyszuk A, Grabowska M, Techmanska I, Juscinska J, et al. Administration of CD4+CD25highCD127- regulatory T cells preserves β-cell function in type 1 diabetes in children. Diabetes Care. 2012;35:1817–20. This paper describes the first study in humans with autologous ex vivo expanded CD4 + CD25high CD127low TRegs in recent onset pediatric T1D patients.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Bluestone JA, Buckner JH, Fitch M, Gitelman SE, Gupta S, Hellerstein MK, et al. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci Transl Med. 2015;7:315ra189. First trial to track infused autologous ex vivo expanded CD4+CD25+CD127low Tregs in patients with T1D.

    Article  PubMed  Google Scholar 

  12. Desreumaux P, Foussat A, Allez M, Beaugerie L, Hébuterne X, Bouhnik Y, et al. Safety and efficacy of antigen-specific regulatory T-cell therapy for patients with refractory Crohn’s disease. Gastroenterology. 2012;143:1207–17.e1-2. This study shows safety and efficacy of autologous ovalbumin-specific Tr1 cells in patients with refractory Crohn’s disease.

    Article  CAS  PubMed  Google Scholar 

  13. Todo S, Yamashita K, Goto R, Zaitsu M, Nagatsu A, Oura T et al. A Pilot study of operational tolerance with a regulatory T cell-based cell therapy in living donor liver transplantation. Hepatology, 2016 (Epub ahead of print). This study reports the first TReg-cell therapy trial in solid organ transplantation showing operational tolerance in seven out of ten liver transplant recipients

  14. Geissler EK. The ONE Study compares cell therapy products in organ transplantation: introduction to a review series on suppressive monocyte-derived cells. Transplant Res. 2012;1:11. This paper introduces The ONE Study which explores feasibility and potential for regulatory cell therapy in living donor kidney transplantation.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Petrelli A, Tresoldi E, Mfarrej BG, Paganelli A, Spotti D, Caldara R, et al. Generation of donor-specific T regulatory type 1 cells from patients on dialysis for cell therapy after kidney transplantation. Transplantation. 2015;99:1582–9.

    Article  CAS  PubMed  Google Scholar 

  16. Sagoo P, Lombardi G, Lechler RI. Relevance of regulatory T cell promotion of donor-specific tolerance in solid organ transplantation. Front Immunol. 2012;3:184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Hutchinson JA, Geissler EK. Now or never? The case for cell-based immunosuppression in kidney transplantation. Kidney Int. 2015;87:1116–24.

    Article  PubMed  Google Scholar 

  18. Battaglia M. Potential T, regulatory cell therapy in transplantation: how far have we come and how far can we go? Transpl Int. 2010;23:761–70.

    Article  CAS  PubMed  Google Scholar 

  19. Wiseman AC. Immunosuppressive medications. Clin J Am Soc Nephrol. 2016;11:332–43.

    Article  PubMed  Google Scholar 

  20. van der Touw W, Bromberg JS. Natural killer cells and the immune response in solid organ transplantation. Am J Transplant. 2010;10:1354–8.

    Article  PubMed  Google Scholar 

  21. Hankey KG, Drachenberg CB, Papadimitriou JC, Klassen DK, Philosophe B, Bartlett ST, et al. MIC expression in renal and pancreatic allografts. Transplantation. 2002;73:304–6.

    Article  CAS  PubMed  Google Scholar 

  22. Venner JM, Hidalgo LG, Famulski KS, Chang J, Halloran PF. The molecular landscape of antibody-mediated kidney transplant rejection: evidence for NK involvement through CD16a Fc receptors. Am J Transplant. 2015;15:1336–48.

    Article  CAS  PubMed  Google Scholar 

  23. Gerosa F, Baldani-Guerra B, Nisii C, Marchesini V, Carra G, Trinchieri G. Reciprocal activating interaction between natural killer cells and dendritic cells. J Exp Med. 2002;195:327–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Ferlazzo G, Tsang ML, Moretta L, Melioli G, Steinman RM, Münz C. Human dendritic cells activate resting natural killer (NK) cells and are recognized via the NKp30 receptor by activated NK cells. J Exp Med. 2002;195:343–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Ghiringhelli F, Ménard C, Terme M, Flament C, Taieb J, Chaput N, et al. CD4+CD25+ regulatory T cells inhibit natural killer cell functions in a transforming growth factor-beta-dependent manner. J Exp Med. 2005;202:1075–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Smyth MJ, Teng MW, Swann J, Kyparissoudis K, Godfrey DI, Hayakawa Y. CD4+CD25+ T regulatory cells suppress NK cell-mediated immunotherapy of cancer. J Immunol. 2006;176:1582–7.

    Article  CAS  PubMed  Google Scholar 

  27. Hirohashi T, Chase CM, DellaPelle P, Sebastian D, Farkesh E, Colvin RB, et al. Depletion of T regulatory cells promotes natural killer cell-mediated cardiac allograft vasculopathy. Transplantation. 2014;98:828–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gasteiger G, Hemmers S, Bos PD, Sun JC, Rudensky AY. IL-2-dependent adaptive control of NK cell homeostasis. J Exp Med. 2013;210:1179–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Sitrin J, Ring A, Garcia KC, Benoist C, Mathis D. Regulatory T cells control NK cells in an insulitic lesion by depriving them of IL-2. J Exp Med. 2013;210:1153–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Ralainirina N, Poli A, Michel T, Poos L, Andrès E, Hentges F, et al. Control of NK cell functions by CD4+CD25+ regulatory T cells. J Leukoc Biol. 2007;81:144–53.

    Article  CAS  PubMed  Google Scholar 

  31. Carman CV, Martinelli R. T lymphocyte-endothelial interactions: emerging understanding of trafficking and antigen-specific immunity. Front Immunol. 2015;6:603.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Choi J, Enis DR, Koh KP, Shiao SL, Pober JS. T lymphocyte-endothelial cell interactions. Annu Rev Immunol. 2004;22:683–709.

    Article  CAS  PubMed  Google Scholar 

  33. Dengler TJ, Pober JS. Human vascular endothelial cells stimulate memory but not naive CD8+ T cells to differentiate into CTL retaining an early activation phenotype. J Immunol. 2000;164:5146–55.

    Article  CAS  PubMed  Google Scholar 

  34. Marelli-Berg FM, Hargreaves RE, Carmichael P, Dorling A, Lombardi G, Lechler RI. Major histocompatibility complex class II-expressing endothelial cells induce allospecific nonresponsiveness in naive T cells. J Exp Med. 1996;183:1603–12.

    Article  CAS  PubMed  Google Scholar 

  35. Lion J, Taflin C, Cross AR, Robledo-Sarmiento M, Mariotto E, Savenay A et al. HLA class II antibody activation of endothelial cells promotes Th17 and disrupts regulatory T lymphocyte expansion. Am J Transplant, 2015 (Epub ahead of print)

  36. Jackson AM, Sigdel TK, Delville M, Hsieh SC, Dai H, Bagnasco S, et al. Endothelial cell antibodies associated with novel targets and increased rejection. J Am Soc Nephrol. 2015;26:1161–71.

    Article  CAS  PubMed  Google Scholar 

  37. Maganto-García E, Bu DX, Tarrio ML, Alcaide P, Newton G, Griffin GK, et al. Foxp3+− inducible regulatory T cells suppress endothelial activation and leukocyte recruitment. J Immunol. 2011;187:3521–9.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Eljaafari A, Badet L, Kanitakis J, Ferrand C, Farre A, Petruzzo P, et al. Isolation of regulatory T cells in the skin of a human hand-allograft, up to six years posttransplantation. Transplantation. 2006;82:1764–8.

    Article  CAS  PubMed  Google Scholar 

  39. Dijke IE, Caliskan K, Korevaar SS, Maat AP, Zondervan PE, Balk AH, et al. FOXP3 mRNA expression analysis in the peripheral blood and allograft of heart transplant patients. Transpl Immunol. 2008;18:250–4.

    Article  CAS  PubMed  Google Scholar 

  40. Dijke IE, Korevaar SS, Caliskan K, Balk AH, Maat AP, Weimar W, et al. Inadequate immune regulatory function of CD4+CD25bright+FoxP3+ T cells in heart transplant patients who experience acute cellular rejection. Transplantation. 2009;87:1191–200.

    Article  PubMed  Google Scholar 

  41. Cyster JG. B cell follicles and antigen encounters of the third kind. Nat Immunol. 2010;11:989–96.

    Article  CAS  PubMed  Google Scholar 

  42. Sarwal M, Chua MS, Kambham N, Hsieh SC, Satterwhite T, Masek M, et al. Molecular heterogeneity in acute renal allograft rejection identified by DNA microarray profiling. N Engl J Med. 2003;349:125–38.

    Article  CAS  PubMed  Google Scholar 

  43. Hippen BE, DeMattos A, Cook WJ, Kew CE, Gaston RS. Association of CD20+ infiltrates with poorer clinical outcomes in acute cellular rejection of renal allografts. Am J Transplant. 2005;5:2248–52.

    Article  PubMed  Google Scholar 

  44. Zarkhin V, Kambham N, Li L, Kwok S, Hsieh SC, Salvatierra O, et al. Characterization of intra-graft B cells during renal allograft rejection. Kidney Int. 2008;74:664–73.

    Article  CAS  PubMed  Google Scholar 

  45. Sagoo P, Perucha E, Sawitzki B, Tomiuk S, Stephens DA, Miqueu P, et al. Development of a cross-platform biomarker signature to detect renal transplant tolerance in humans. J Clin Invest. 2010;120:1848–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Newell KA, Asare A, Kirk AD, Gisler TD, Bourcier K, Suthanthiran M, et al. Identification of a B cell signature associated with renal transplant tolerance in humans. J Clin Invest. 2010;120:1836–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Lim HW, Hillsamer P, Kim CH. Regulatory T cells can migrate to follicles upon T cell activation and suppress GC-Th cells and GC-Th cell-driven B cell responses. J Clin Invest. 2004;114:1640–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Lim HW, Hillsamer P, Banham AH, Kim CH. Cutting edge: direct suppression of B cells by CD4+ CD25+ regulatory T cells. J Immunol. 2005;175:4180–3.

    Article  CAS  PubMed  Google Scholar 

  49. Xu A, Liu Y, Chen W, Wang J, Xue Y, Huang F et al. TGF-β-induced regulatory T cells directly suppress B cell responses through a noncytotoxic mechanism. J Immunol, 2016 (Epub ahead of print).

  50. Clemente-Casares X, Blanco J, Ambalavanan P, Yamanouchi J, Singha S, Fandos C, et al. Expanding antigen-specific regulatory networks to treat autoimmunity. Nature. 2016;530:434–40.

    Article  CAS  PubMed  Google Scholar 

  51. Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med. 1969;280:735–9.

    Article  CAS  PubMed  Google Scholar 

  52. Collins AB, Schneeberger EE, Pascual MA, Saidman SL, Williams WW, Tolkoff-Rubin N, et al. Complement activation in acute humoral renal allograft rejection: diagnostic significance of C4d deposits in peritubular capillaries. J Am Soc Nephrol. 1999;10:2208–14.

    CAS  PubMed  Google Scholar 

  53. Loupy A, Lefaucheur C, Vernerey D, Prugger C, Duong van Huyen JP, Mooney N, et al. Complement-binding anti-HLA antibodies and kidney-allograft survival. N Engl J Med. 2013;369:1215–26.

    Article  CAS  PubMed  Google Scholar 

  54. Mathern DR, Heeger PS. Molecules great and small: the complement system. Clin J Am Soc Nephrol. 2015;10:1636–50.

    Article  CAS  PubMed  Google Scholar 

  55. van der Touw W, Cravedi P, Kwan WH, Paz-Artal E, Merad M, Heeger PS. Cutting edge: receptors for C3a and C5a modulate stability of alloantigen-reactive induced regulatory T cells. J Immunol. 2013;190:5921–5.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Kerjaschki D, Regele HM, Moosberger I, Nagy-Bojarski K, Watschinger B, Soleiman A, et al. Lymphatic neoangiogenesis in human kidney transplants is associated with immunologically active lymphocytic infiltrates. J Am Soc Nephrol. 2004;15:603–12.

    Article  CAS  PubMed  Google Scholar 

  57. Drayton DL, Liao S, Mounzer RH, Ruddle NH. Lymphoid organ development: from ontogeny to neogenesis. Nat Immunol. 2006;7:344–53.

    Article  CAS  PubMed  Google Scholar 

  58. Thaunat O, Field AC, Dai J, Louedec L, Patey N, Bloch MF, et al. Lymphoid neogenesis in chronic rejection: evidence for a local humoral alloimmune response. Proc Natl Acad Sci U S A. 2005;102:14723–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Thaunat O, Patey N, Caligiuri G, Gautreau C, Mamani-Matsuda M, Mekki Y, et al. Chronic rejection triggers the development of an aggressive intragraft immune response through recapitulation of lymphoid organogenesis. J Immunol. 2010;185:717–28.

    Article  CAS  PubMed  Google Scholar 

  60. Xu X, Han Y, Wang Q, Cai M, Qian Y, Wang X, et al. Characterisation of tertiary lymphoid organs in explanted rejected donor kidneys. Immunol Invest. 2016;45:38–51.

    Article  CAS  PubMed  Google Scholar 

  61. Brown K, Sacks SH, Wong W. Tertiary lymphoid organs in renal allografts can be associated with donor-specific tolerance rather than rejection. Eur J Immunol. 2011;41:89–96.

    Article  CAS  PubMed  Google Scholar 

  62. Hsiao HM, Li W, Gelman AE, Krupnick AS, Kreisel D. The role of lymphoid neogenesis in allografts. Am J Transplant. 2016;16:1079–85.

    Article  CAS  PubMed  Google Scholar 

  63. Lakkis FG, Sayegh MH. Memory T cells: a hurdle to immunologic tolerance. J Am Soc Nephrol. 2003;14:2402–10.

    Article  PubMed  Google Scholar 

  64. Tchao NK, Turka LA. Lymphodepletion and homeostatic proliferation: implications for transplantation. Am J Transplant. 2012;12:1079–90.

    Article  CAS  PubMed  Google Scholar 

  65. Espinosa JR, Samy KP, Kirk AD. Memory T cells in organ transplantation: progress and challenges. Nat Rev Nephrol, 2016 (Epub ahead of print).

  66. Macedo C, Orkis EA, Popescu I, Elinoff BD, Zeevi A, Shapiro R, et al. Contribution of naïve and memory T-cell populations to the human alloimmune response. Am J Transplant. 2009;9:2057–66.

    Article  CAS  PubMed  Google Scholar 

  67. Heeger PS, Greenspan NS, Kuhlenschmidt S, Dejelo C, Hricik DE, Schulak JA, et al. Pretransplant frequency of donor-specific, IFN-gamma-producing lymphocytes is a manifestation of immunologic memory and correlates with the risk of posttransplant rejection episodes. J Immunol. 1999;163:2267–75.

    CAS  PubMed  Google Scholar 

  68. Bestard O, Nickel P, Cruzado JM, Schoenemann C, Boenisch O, Sefrin A, et al. Circulating alloreactive T cells correlate with graft function in longstanding renal transplant recipients. J Am Soc Nephrol. 2008;19:1419–29.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Chen W, Ghobrial RM, Li XC. The evolving roles of memory immune cells in transplantation. Transplantation. 2015;99:2029–37.

    Article  CAS  PubMed  Google Scholar 

  70. Yang J, Brook MO, Carvalho-Gaspar M, Zhang J, Ramon HE, Sayegh MH, et al. Allograft rejection mediated by memory T cells is resistant to regulation. Proc Natl Acad Sci U S A. 2007;104:19954–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Afzali B, Mitchell PJ, Scottà C, Canavan J, Edozie FC, Fazekasova H, et al. Relative resistance of human CD4(+) memory T cells to suppression by CD4(+) CD25(+) regulatory T cells. Am J Transplant. 2011;11:1734–42.

    Article  CAS  PubMed  Google Scholar 

  72. Jones ND, Brook MO, Carvalho-Gaspar M, Luo S, Wood KJ. Regulatory T cells can prevent memory CD8+ T-cell-mediated rejection following polymorphonuclear cell depletion. Eur J Immunol. 2010;40:3107–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Krummey SM, Ford ML. Heterogeneity within T cell memory: implications for transplant tolerance. Front Immunol. 2012;3:36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Levings MK, Sangregorio R, Roncarolo MG. Human cd25(+)cd4(+) T regulatory cells suppress naive and memory T cell proliferation and can be expanded in vitro without loss of function. J Exp Med. 2001;193:1295–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Brunstein CG, Miller JS, Cao Q, McKenna DH, Hippen KL, Curtsinger J, et al. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood. 2011;117:1061–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Lin KL, Fulton LM, Berginski M, West ML, Taylor NA, Moran TP, et al. Intravital imaging of donor allogeneic effector and regulatory T cells with host dendritic cells during GVHD. Blood. 2014;123:1604–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Cohen CD, Gröne HJ, Gröne EF, Nelson PJ, Schlöndorff D, Kretzler M. Laser microdissection and gene expression analysis on formaldehyde-fixed archival tissue. Kidney Int. 2002;61:125–32.

    Article  CAS  PubMed  Google Scholar 

  78. Vergani A, Clissi B, Sanvito F, Doglioni C, Fiorina P, Pardi R. Laser capture microdissection as a new tool to assess graft-infiltrating lymphocytes gene profile in islet transplantation. Cell Transplant. 2009;18:827–32.

    Article  CAS  PubMed  Google Scholar 

  79. Gaughan A, Wang J, Pelletier RP, Nadasdy T, Brodsky S, Roy S, et al. Key role for CD4 T cells during mixed antibody-mediated rejection of renal allografts. Am J Transplant. 2014;14:284–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Manuela Battaglia was funded by the 7th framework programme of the EU (FP7-HEALTH) and the Italian Ministry of Health and Juvenile Diabetes Research Foundation (JDRF). Bechara Mfarrej was supported by the 7th framework programme of the EU (Marie Curie Initial Training Network -FP7-PEOPLE-2011-ITN), under the Marie Skłodowska-Curie grant agreement No 289903: EUTRAIN.

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Mfarrej, B.G., Battaglia, M. The “Unusual Suspects” in Allograft Rejection: Will T Regulatory Cell Therapy Arrest Them?. Curr Transpl Rep 3, 221–226 (2016). https://doi.org/10.1007/s40472-016-0108-7

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