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Introduction to Immunosuppression, Tolerance, and Infection Risk

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Emerging Transplant Infections
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Abstract

Over the last half a century, there have been innumerable advances in our understanding of the human immune system. We now have a better understanding not only of the ways our innate and adaptive immune pathways interact to seek out and control infection and malignancy, but we are closer to understanding some of the control mechanisms behind tissue rejection. Organ allograft rejection, with consequent loss of graft function, remains one of the most challenging problems facing solid organ allotransplantation. Developments in therapeutic immunosuppression have enabled us to minimize rejection risk and improve the life expectancy and graft survival for many of our patients, but at a cost: the more intense the immunosuppression, typically the greater the infection risk. Ultimately, the field continues to work towards ways of achieving organ tolerance whereby both rejection risk and the threats of infection are minimized.

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References

  1. Linden P. History of solid organ transplantation and organ donation. Crit Care Clin. 2009;25(1):165–84.

    Article  Google Scholar 

  2. De Vito Dabbs A, Dauber JH, Hoffman LA. Rejection after organ transplantation: a historical review. Am J Crit Care. 2000;9(6):419–29.

    Article  Google Scholar 

  3. Transplant Pioneers Recall Medical Milestone. NPR. December 20, 2004. Retrieved 20 Dec 2019.

    Google Scholar 

  4. Chen J, Li J, Wu Q. Maintenance of naïve CD8 T cells in nonagenarians by leptin, IGFBP3 and T3. Mech Ageing Dev. 2010;131(1):29–37.

    Article  CAS  Google Scholar 

  5. Lim M, Kohli J, Blood R. Immunosuppression for kidney transplantation: where are we now and where are we going? Transplant Rev. 2017;31(1):10–7.

    Article  Google Scholar 

  6. Cruse J, Lewis R, Wang H. Immunology guidebook. Amsterdam: Academic; 2004. p. 267–76.

    Google Scholar 

  7. DeWolf S, Sykes M. Alloimmune T cells in transplantation. J Clin Invest. 2017;127(7): 2473–81.

    Article  Google Scholar 

  8. De Bruyn P, Van Gestel D, Ost P, et al. Immune checkpoint blockade for organ transplant patients with advanced cancer: how far can we go? Curr Opin Oncol. 2019;31(2):54–64.

    Article  Google Scholar 

  9. Hart A, Smith JM, Skeans MA, et al. OPTN/SRTR 2015 annual data report: kidney. Am J Transplant. 2017;17(Suppl 1):21–116.

    Article  Google Scholar 

  10. Witt CA, Gaut JP, Yusen RD, Byers DE, Iuppa JA, Bennett Bain K, Alexander Patterson G, Mohanakumar T, Trulock EP, Hachem RR. Acute antibody-mediated rejection after lung transplantation. J Heart Lung Transplant. 2013;32(10):1034–40. Epub 2013 Aug 13.

    Article  Google Scholar 

  11. Zhang SY, Jouanguy E, Sancho-Shimizu V, et al. Human toll-like receptor-dependent induction of interferons in protective immunity to viruses. Immunol Rev. 2007;220(1):225–36.

    Article  CAS  Google Scholar 

  12. Zhao H, Alam A, Soo AP, George AJT, Ma D. Ischemia-reperfusion injury reduces long term renal graft survival: mechanism and beyond. EBioMedicine. 2018;28:31–42.

    Article  Google Scholar 

  13. Lu C, Penfield J, Kielar M, Vazquez M, Jeyarajah R. Hypothesis: is renal allograft rejection initiated by the response to injury sustained during the transplant process? Kidney Int. 1999;55(6):2157–68.

    Article  CAS  Google Scholar 

  14. Villard J. The role of natural killer cells in human solid organ and tissue transplantation. J Innate Immun. 2011;3(4):395–402.

    Article  Google Scholar 

  15. Benichou G, Yamada Y, Aoyama A, Madsen J. Natural killer cells in rejection and tolerance of solid organ allografts. Curr Opin Organ Transplant. 2011;16(1):47–53.

    Article  CAS  Google Scholar 

  16. Yu G, Xu X, Vu MD, Kilpatrick ED, Li XC. NK cells promote transplant tolerance by killing donor antigen-presenting cells. J Exp Med. 2006;203(8):1851–8.

    Article  CAS  Google Scholar 

  17. Surana N, Kasper K. Deciphering the tete-a-tete between the microbiota and the immune system. J Clin Invest. 2014;124(10):4197–203.

    PubMed  PubMed Central  Google Scholar 

  18. Wiederrecht G, Lam E, Hung S, Martin M, Sigal N. The mechanism of action of FK-506 and cyclosporin A. Ann N Y Acad Sci. 1993;696:9–19.

    Article  CAS  Google Scholar 

  19. Allison AC, Eugui EM. Mycophenolate mofetil and its mechanisms of action. Immunopharmacology. 2000;47(2–3):85–118.

    Article  CAS  Google Scholar 

  20. Sandborn WJ. A review of immune modifier therapy for inflammatory bowel disease: azathioprine, 6-mercaptopurine, cyclosporine, and methotrexate. Am J Gastroenterol. 1996;91(3): 423–33.

    CAS  PubMed  Google Scholar 

  21. Kelly PA, Gruber SA, Behbod F, Kahan BD. Sirolimus, a new, potent immunosuppressive agent. Pharmacotherapy. 1997;17(6):1148–56.

    CAS  PubMed  Google Scholar 

  22. Almawi WY, Beyhum HN, Rahme AA, Rieder MJ. Regulation of cytokine and cytokine receptor expression by glucocorticoids. J Leukoc Biol. 1996;60(5):563.

    Article  CAS  Google Scholar 

  23. Sam T, Gabardi S, Tichy EM. Risk evaluation and mitigation strategies: a focus on belatacept. Prog Transplant. 2013;23(1):64–70.

    Article  Google Scholar 

  24. Nulojix. (webpage) Risk evaluation and mitigation strategy for increased risk of PTLD, predominantly involving the CNS, and PML with NULOJIX. Available from http://www.nulojix.com/hcp/rems.aspx?cm_mc_uid=03785373987414557419388&cm_mc_sid_51110000=1459792841

  25. Liu CL, Fan ST, Lo CM, et al. Interleukin-2 receptor antibody (basiliximab) for immunosuppressive induction therapy after liver transplantation: a protocol with early elimination of steroids and reduction of tacrolimus dosage. Liver Transpl. 2004;10(6):728–33.

    Article  Google Scholar 

  26. Hanaway MJ, Woodle ES, Mulgaonkar S, et al. Alemtuzumab induction in renal transplantation. N Engl J Med. 2011;364(20):1909–19.

    Article  CAS  Google Scholar 

  27. Bhorade SM, Stern E. Immunosuppression for lung transplantation. Proc Am Thorac Soc. 2009;6(1):47–53.

    Article  CAS  Google Scholar 

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Correspondence to Cameron R. Wolfe .

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Wolfe, C.R. (2021). Introduction to Immunosuppression, Tolerance, and Infection Risk. In: Morris, M.I., Kotton, C.N., Wolfe, C.R. (eds) Emerging Transplant Infections. Springer, Cham. https://doi.org/10.1007/978-3-030-25869-6_2

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  • DOI: https://doi.org/10.1007/978-3-030-25869-6_2

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-25868-9

  • Online ISBN: 978-3-030-25869-6

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