Mất sự tự chấp nhận sau ghép tạng

Springer Science and Business Media LLC - Tập 33 - Trang 105-110 - 2011
Melissa R. Keller1, William J. Burlingham1
1Department of Surgery, University of Wisconsin, Madison, USA

Tóm tắt

Ghép tạng là phương pháp điều trị được chấp nhận rộng rãi cho các trường hợp suy tạng ở giai đoạn cuối. Kể từ ca ghép thận thành công đầu tiên từ một người hiến tạng là anh em sinh đôi vào năm 1954, các nhà nghiên cứu đã tiến hành nghiên cứu ảnh hưởng của hệ thống miễn dịch đến kết quả ghép tạng. Mặc dù phẫu thuật đã thành công về mặt kĩ thuật, phần lớn các mô ghép từ những người hiến tạng khác gen đều bị từ chối do một số yếu tố kích thích phản ứng miễn dịch của người nhận, dẫn đến mất mô ghép mặc dù đã sử dụng thuốc ức chế miễn dịch (IS) một cách mãn tính. Đáng tiếc, trong khi thành công ngắn hạn đã được cải thiện đáng kể bởi sự phát triển của các loại thuốc IS mới, tỷ lệ sống sót của mô ghép các cơ quan rắn trong thời gian dài không được cải thiện đáng kể trong vài thập kỷ qua. Vấn đề mất mô ghép muộn chủ yếu được cho là do sự phát triển của sự từ chối mãn tính. Do đó, việc hiểu rõ tất cả các cơ chế miễn dịch liên quan đến sự từ chối ghép là rất quan trọng để ngăn ngừa sự rối loạn chức năng mô ghép, và cuối cùng là mất mô ghép. Trong bài tổng quan này, chúng tôi sẽ cung cấp cái nhìn tổng quan về sự từ chối mô ghép, quá trình từ sự từ chối cấp tính đến mãn tính, và bên cạnh đó, sự phát hiện gần đây về vai trò quan trọng của sự mất tự chấp nhận và sự phát triển của tự miễn dịch phụ thuộc IL-17 trong sự từ chối mãn tính.

Từ khóa

#ghép tạng #hệ miễn dịch #sự từ chối mô ghép #thuốc ức chế miễn dịch #tự miễn dịch

Tài liệu tham khảo

Halloran PF, Homik J, Goes N et al (1997) The "injury response": a concept linking nonspecific injury, acute rejection, and long-term transplant outcomes. Transplant Proc 29:79–81 Merrill JP, Murray JE, Harrison JH et al (1956) Successful homotransplantation of the human kidney between identical twins. J Am Med Assoc 160:277–282 Boros P, Bromberg JS (2008) De novo autoimmunity after organ transplantation: targets and possible pathways. Hum Immunol 69:383–388 He H, Stone JR, Perkins DL (2002) Analysis of robust innate immune response after transplantation in the absence of adaptive immunity. Transplantation 73:853–861 Chalasani G, Li Q, Konieczny BT et al (2004) The allograft defines the type of rejection (acute versus chronic) in the face of an established effector immune response. J Immunol 172:7813–7820 Palmer SM, Burch LH, Trindade AJ et al (2005) Innate immunity influences long-term outcomes after human lung transplant. Am J Respir Crit Care Med 171:780–785 Goulding NJ, Guyre PM (1993) Glucocorticoids, lipocortins and the immune response. Curr Opin Immunol 5:108–113 Warrens AN, Lombardi G, Lechler RI (1994) Presentation and recognition of major and minor histocompatibility antigens. Transpl Immunol 2:103–107 Dierselhuis M, Goulmy E (2009) The relevance of minor histocompatibility antigens in solid organ transplantation. Curr Opin Organ Transplant 14:419–425 Tiede I, Fritz G, Strand S et al (2003) CD28-dependent Rac1 activation is the molecular target of azathioprine in primary human CD4+ T lymphocytes. J Clin Invest 111:1133–1145 Brazelton TR, Morris RE (1996) Molecular mechanisms of action of new xenobiotic immunosuppressive drugs: tacrolimus (FK506), sirolimus (rapamycin), mycophenolate mofetil and leflunomide. Curr Opin Immunol 8:710–720 Barnes PJ (2006) Corticosteroids: the drugs to beat. Eur J Pharmacol 533:2–14 Diekmann F, Rovira J, Carreras J et al (2007) Mammalian target of rapamycin inhibition halts the progression of proteinuria in a rat model of reduced renal mass. J Am Soc Nephrol 18:2653–2660 Burke CM, Theodore J, Dawkins KD et al (1984) Post-transplant obliterative bronchiolitis and other late lung sequelae in human heart-lung transplantation. Chest 86:824–829 Verleden GM (2001) Chronic allograft rejection (obliterative bronchiolitis). Semin Respir Crit Care Med 22:551–558 Knoop C, Estenne M (2006) Acute and chronic rejection after lung transplantation. Semin Respir Crit Care Med 27:521–533 Wood KJ, Sakaguchi S (2003) Regulatory T cells in transplantation tolerance. Nat Rev Immunol 3:199–210 Lombardi G, Sidhu S, Batchelor JR et al (1989) Allorecognition of DR1 by T cells from a DR4/DRw13 responder mimics self-restricted recognition of endogenous peptides. Proc Natl Acad Sci USA 86:4190–4194 Benichou G, Takizawa PA, Olson CA et al (1992) Donor major histocompatibility complex (MHC) peptides are presented by recipient MHC molecules during graft rejection. J Exp Med 175:305–308 Herrera OB, Golshayan D, Tibbott R et al (2004) A novel pathway of alloantigen presentation by dendritic cells. J Immunol 173:4828–4837 Parker KE, Dalchau R, Fowler VJ et al (1992) Stimulation of CD4+ T lymphocytes by allogeneic MHC peptides presented on autologous antigen-presenting cells. Evidence of the indirect pathway of allorecognition in some strain combinations. Transplantation 53:918–924 Ciubotariu R, Liu Z, Colovai AI et al (1998) Persistent allopeptide reactivity and epitope spreading in chronic rejection of organ allografts. J Clin Invest 101:398–405 Auchincloss H Jr, Lee R, Shea S et al (1993) The role of "indirect" recognition in initiating rejection of skin grafts from major histocompatibility complex class II-deficient mice. Proc Natl Acad Sci USA 90:3373–3377 VanBuskirk AM, Burlingham WJ, Jankowska-Gan E et al (2000) Human allograft acceptance is associated with immune regulation. J Clin Invest 106:145–155 Colvin RB, Smith RN (2005) Antibody-mediated organ-allograft rejection. Nat Rev Immunol 5:807–817 Moll S, Pascual M (2005) Humoral rejection of organ allografts. Am J Transplant 5:2611–2618 Fedoseyeva EV, Zhang F, Orr PL et al (1999) De novo autoimmunity to cardiac myosin after heart transplantation and its contribution to the rejection process. J Immunol 162:6836–6842 Nadeau KC, Azuma H, Tilney NL (1995) Sequential cytokine dynamics in chronic rejection of rat renal allografts: roles for cytokines RANTES and MCP-1. Proc Natl Acad Sci USA 92:8729–8733 Rocha PN, Plumb TJ, Crowley SD et al (2003) Effector mechanisms in transplant rejection. Immunol Rev 196:51–64 D'Elios MM, Josien R, Manghetti M et al (1997) Predominant Th1 cell infiltration in acute rejection episodes of human kidney grafts. Kidney Int 51:1876–1884 Chan SY, DeBruyne LA, Goodman RE et al (1995) In vivo depletion of CD8+ T cells results in Th2 cytokine production and alternate mechanisms of allograft rejection. Transplantation 59:1155–1161 Fossiez F, Banchereau J, Murray R et al (1998) Interleukin-17. Int Rev Immunol 16:541–551 Antonysamy MA, Fanslow WC, Fu F et al (1999) Evidence for a role of IL-17 in organ allograft rejection: IL-17 promotes the functional differentiation of dendritic cell progenitors. J Immunol 162:577–584 Yuan X, Paez-Cortez J, Schmitt-Knosalla I et al (2008) A novel role of CD4 Th17 cells in mediating cardiac allograft rejection and vasculopathy. J Exp Med 205:3133–3144 Burrell BE, Csencsits K, Lu G et al (2008) CD8+ Th17 mediate costimulation blockade-resistant allograft rejection in T-bet-deficient mice. J Immunol 181:3906–3914 Azuma H, Chandraker A, Nadeau K et al (1996) Blockade of T-cell costimulation prevents development of experimental chronic renal allograft rejection. Proc Natl Acad Sci USA 93:12439–12444 Burlingham WJ, Love RB, Jankowska-Gan E et al (2007) IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants. J Clin Invest 117:3498–3506 Fukami N, Ramachandran S, Saini D et al (2009) Antibodies to MHC class I induce autoimmunity: role in the pathogenesis of chronic rejection. J Immunol 182:309–318 Rolls HK, Kishimoto K, Dong VM et al (2002) T-cell response to cardiac myosin persists in the absence of an alloimmune response in recipients with chronic cardiac allograft rejection. Transplantation 74:1053–1057 Barber LD, Whitelegg A, Madrigal JA et al (2004) Detection of vimentin-specific autoreactive CD8+ T cells in cardiac transplant patients. Transplantation 77:1604–1609 Carter V, Shenton BK, Jaques B et al (2005) Vimentin antibodies: a non-HLA antibody as a potential risk factor in renal transplantation. Transplant Proc 37:654–657 Linsenmayer TF, Gibney E, Igoe F et al (1993) Type V collagen: molecular structure and fibrillar organization of the chicken alpha 1(V) NH2-terminal domain, a putative regulator of corneal fibrillogenesis. J Cell Biol 121:1181–1189 Wilkes DS, Heidler KM, Niemeier M et al (1994) Increased bronchoalveolar IgG2/IgG1 ratio is a marker for human lung allograft rejection. J Investig Med 42:652–659 Wilkes DS, Heidler KM, Bowen LK et al (1995) Allogeneic bronchoalveolar lavage cells induce the histology of acute lung allograft rejection, and deposition of IgG2a in recipient murine lungs. J Immunol 155:2775–2783 Haque MA, Mizobuchi T, Yasufuku K et al (2002) Evidence for immune responses to a self-antigen in lung transplantation: role of type V collagen-specific T cells in the pathogenesis of lung allograft rejection. J Immunol 169:1542–1549 Yoshida S, Haque A, Mizobuchi T et al (2006) Anti-type V collagen lymphocytes that express IL-17 and IL-23 induce rejection pathology in fresh and well-healed lung transplants. Am J Transplant 6:724–735 Bobadilla JL, Love RB, Jankowska-Gan E et al (2008) TH-17, monokines, collagen type V, and primary graft dysfunction in lung transplantation. Am J Respir Crit Care Med 177:660–668 Goers TA, Ramachandran S, Aloush A et al (2008) De novo production of K-alpha1 tubulin-specific antibodies: role in chronic lung allograft rejection. J Immunol 180:4487–4494 Wood KL, Nunley DR, Moffatt-Bruce S et al (2010) The role of heat shock protein 27 in bronchiolitis obliterans syndrome after lung transplantation. J Heart Lung Transplant 29:786–791 Lehmann PV, Forsthuber T, Miller A et al (1992) Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature 358:155–157 Vanderlugt CL, Miller SD (2002) Epitope spreading in immune-mediated diseases: implications for immunotherapy. Nat Rev Immunol 2:85–95 Yasufuku K, Heidler KM, O'Donnell PW et al (2001) Oral tolerance induction by type V collagen downregulates lung allograft rejection. Am J Respir Cell Mol Biol 25:26–34 McMahon EJ, Bailey SL, Castenada CV et al (2005) Epitope spreading initiates in the CNS in two mouse models of multiple sclerosis. Nat Med 11:335–339 Jordan MS, Boesteanu A, Reed AJ et al (2001) Thymic selection of CD4 + CD25+ regulatory T cells induced by an agonist self-peptide. Nat Immunol 2:301–306 Fontenot JD, Gavin MA, Rudensky AY (2003) Foxp3 programs the development and function of CD4 + CD25+ regulatory T cells. Nat Immunol 4:330–336 Baecher-Allan C, Hafler DA (2006) Human regulatory T cells and their role in autoimmune disease. Immunol Rev 212:203–216 Voo KS, Wang YH, Santori FR et al (2009) Identification of IL-17-producing FOXP3+ regulatory T cells in humans. Proc Natl Acad Sci USA 106:4793–4798 Bettelli E, Carrier Y, Gao W et al (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–238 Dart ML, Jankowska-Gan E, Huang G et al (2010) Interleukin-17-dependent autoimmunity to collagen type V in atherosclerosis. Circ Res 107:1106–1116