International Reviews of Immunology, 33:159–161, 2014 C Informa Healthcare USA, Inc. Copyright ISSN: 0883-0185 print / 1563-5244 online DOI: 10.3109/08830185.2014.913442
EDITORIAL
In this Issue: Transplant Immunology and Transplant Biology
Int Rev Immunol Downloaded from informahealthcare.com by Kainan University on 04/20/15 For personal use only.
Lucian P. Jiga1 and Mihai Oltean2 1
University Department for Plastic, Reconstructive and Aesthetic Surgery, Hand Surgery, Evangelisches Krankenhaus, School of Medicine and Health Sciences, Carl von Ossietzky University, Oldenburg, Germany; 2 The Transplantation Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
Transplantation faces an unprecedented shortage of organs available for transplantation, resulting in longer waiting times and transplant candidates on the waiting list dying before getting a transplant. This dramatic situation triggered the search for new approaches and innovations to increase the donor pool, such as extending the acceptance criteria concerning donor age or organ transplantation across blood group barriers. Herein, leading experts detailed the immunological and molecular concepts behind the successful clinical translation of these strategies. Organ rejection remains a constant challenge and transplantation tolerance is still elusive as the current paradigm aims for immunosuppression rather than immune modulation. Two contributions in this issue review two different molecular paradigms in harnessing the immunologic response after transplantation. The interplay between the intestinal innate and adaptive immunity is particularly intricate and the intestine remains the organ with the highest rate of acute rejection after transplantation. Experts in the field summarized both time-honored and recent knowledge in intestinal preservation and tolerance in intestinal transplantation with potential for further basic and translational research. Keywords immunobiology, blood groups, organ transplantation, intestine
Organ transplantation is one of the greatest success stories in modern medicine. During less than 40 years transplantation evolved from a risky surgical endeavor to an established therapy and daily routine, saving the lives of thousands and thousands of patients ailing from end-stage organ failure. The combination between the ever increasing number of patients referred for transplantation and the relative constant number of organ donors generated an enlarging gap between demand and supply. This translated into longer waiting time for an organ transplant with poorer results after transplantation [1], worse quality of life and even death of transplant candidates while awaiting for an organ. Coping with the increasing organ demand and addressing this discrepancy required the expansion of the criteria used for organ donation to individuals previously considered unsuitable for organ donation, (older donors, donors with certain co-morbidities, donors after cardiac death) or the search for innovations allowing ABO-incompatible organ transplants. In this issue, Holgersson et al. reviews the Accepted 7 April 2014. Address correspondence to Mihai Oltean, M.D., Ph.D., The Transplantation Institute, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden. E-mail: [email protected]
Int Rev Immunol Downloaded from informahealthcare.com by Kainan University on 04/20/15 For personal use only.
L. P. Jiga and M. Oltean
molecular basis of blood group determinants as applied to organ transplantation. The review summarizes the past work and current knowledge on blood group antigens structure and alterations stemming from glycobiology research. The seminal findings reviewed herein paved the way for groundbreaking advances in immunoadsorption and allowed ABO-incompatible kidney transplantation to become an established routine at many centers across the world. Elderly represent a fast growing group both as organ donors and recipients. Besides age-related changes at organ level (i.e. glomerulosclerosis) ageing entails a complex and continuous remodeling of the immune system with aging. In this issue, Martins et al. reviews the distinctive features of handling an aging immune system in transplantation and provides insights into the immunosenescence processes in both transplant and nontransplant setting. The authors complete their review by discussing the clinical strategies currently being explored including optimal donor-recipient matching and several experimental immunomodulatory approaches that may provide starting points for additional tailoring and improvements. CD28, CTLA-4 and PD-L1, the three identified ligands for the B7 antigen receptors (CD80, CD86) are pivotal positive and negative costimulatory molecules controlling T cell mobility and the “immune synapse” between dendritic cells and T cells during alloimmune activation after organ transplantation [2]. Accumulating evidence from both experimental and clinical studies indicate that costimulation blockade using mainly monoclonal antibodies can lead to allospecific T-cell anergy and immune unresponsiveness. Envisioning the future, in this issue, Esposito et al. are reviewing the current knowledge on costimulation blockade and new therapeutic approaches aiming to modulate this signaling pathway toward immune tolerance, in the context of kidney transplantation. Induced CD4+ CD25+ FoxP3+ T-regulatory cells (iTregs) have been extensively proved to attain critical roles in immune activation after solid organ transplantation [3]. Within this process, IFNg holds key functions in both induction of Tregs as well as modulation of their immunosuppressive activity. Here, Daniel et al. are reviewing the actual knowledge on IFNg+ Tregs and provide new evidence regarding a distinct subset of IFNg-producing iTregs evaluating their potential as diagnostic (e.g. clinical rejection predictors) as well as therapeutic targets in organ transplantation. The results of clinical intestinal transplantation have continuously improved over the last decade due to several factors including new immunosuppressive strategies aiming at immune modulation rather than immune suppression [4]. Despite normally being the site oral tolerance, the intestine is far from achieving transplantation tolerance itself due to the several causes including the abundant donor-derived lymphoid tissue or the presence of HLA class II on the enterocytes. Meyer et al. provides a comprehensive review of the experimental approaches and clinical trials increasing the knowledge on mechanisms and strategies that favor the establishment of intestinal tolerance towards foreign antigens. An advanced preservation injury of the intestine may favor life threatening infectious complications due to the loss of the mucosal barrier and subsequent bacterial translocation. Moreover, an advanced ischemic injury may release danger signals that may further amplify the immune response toward the graft. In the last review of this issue, Drs. Oltean and Churchill summarize the current knowledge on intestinal preservation injury and briefly review the intestinal cold storage strategies. focusing on luminal preservation strategies as superior and feasible additional alternatives. The authors advocate for this approach with great translational potential and detail several alternative solutions that may be considered in future clinical trials.
International Reviews of Immunology
Transplant Immunology and Transplant Biology
Declaration of Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
Int Rev Immunol Downloaded from informahealthcare.com by Kainan University on 04/20/15 For personal use only.
REFERENCES [1] Meier-Kriesche HU, Kaplan B. Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes—a paired donor kidney analysis. Transplantation 2002;74:1377–1381. [2] Dilek N, Poirier N, Hulin P, et al. Targeting CD28, CTLA-4 and PD-L1 costimulation differentially controls immune synapses and function of human regulatory and conventional T-cells. PLoS One 2013;8(12): e83139. [3] Juvet SC, Whatcott AG, Bushell AR, Wood KJ. Harnessing regulatory T cells for clinical use in transplantation: the end of the beginning. Am J Transplant 2014;14:750–763. [4] Abu-Elmagd KM, Costa G, Bond GJ, et al. Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges. Ann Surg 2009;250:567–581.
C Informa Healthcare USA, Inc. Copyright
EDITORIAL
In this Issue: Transplant Immunology and Transplant Biology
Int Rev Immunol Downloaded from informahealthcare.com by Kainan University on 04/20/15 For personal use only.
Lucian P. Jiga1 and Mihai Oltean2 1
University Department for Plastic, Reconstructive and Aesthetic Surgery, Hand Surgery, Evangelisches Krankenhaus, School of Medicine and Health Sciences, Carl von Ossietzky University, Oldenburg, Germany; 2 The Transplantation Institute, Sahlgrenska University Hospital, Gothenburg, Sweden
Transplantation faces an unprecedented shortage of organs available for transplantation, resulting in longer waiting times and transplant candidates on the waiting list dying before getting a transplant. This dramatic situation triggered the search for new approaches and innovations to increase the donor pool, such as extending the acceptance criteria concerning donor age or organ transplantation across blood group barriers. Herein, leading experts detailed the immunological and molecular concepts behind the successful clinical translation of these strategies. Organ rejection remains a constant challenge and transplantation tolerance is still elusive as the current paradigm aims for immunosuppression rather than immune modulation. Two contributions in this issue review two different molecular paradigms in harnessing the immunologic response after transplantation. The interplay between the intestinal innate and adaptive immunity is particularly intricate and the intestine remains the organ with the highest rate of acute rejection after transplantation. Experts in the field summarized both time-honored and recent knowledge in intestinal preservation and tolerance in intestinal transplantation with potential for further basic and translational research. Keywords immunobiology, blood groups, organ transplantation, intestine
Organ transplantation is one of the greatest success stories in modern medicine. During less than 40 years transplantation evolved from a risky surgical endeavor to an established therapy and daily routine, saving the lives of thousands and thousands of patients ailing from end-stage organ failure. The combination between the ever increasing number of patients referred for transplantation and the relative constant number of organ donors generated an enlarging gap between demand and supply. This translated into longer waiting time for an organ transplant with poorer results after transplantation [1], worse quality of life and even death of transplant candidates while awaiting for an organ. Coping with the increasing organ demand and addressing this discrepancy required the expansion of the criteria used for organ donation to individuals previously considered unsuitable for organ donation, (older donors, donors with certain co-morbidities, donors after cardiac death) or the search for innovations allowing ABO-incompatible organ transplants. In this issue, Holgersson et al. reviews the Accepted 7 April 2014. Address correspondence to Mihai Oltean, M.D., Ph.D., The Transplantation Institute, Sahlgrenska University Hospital, 413 45, Gothenburg, Sweden. E-mail: [email protected]
Int Rev Immunol Downloaded from informahealthcare.com by Kainan University on 04/20/15 For personal use only.
L. P. Jiga and M. Oltean
molecular basis of blood group determinants as applied to organ transplantation. The review summarizes the past work and current knowledge on blood group antigens structure and alterations stemming from glycobiology research. The seminal findings reviewed herein paved the way for groundbreaking advances in immunoadsorption and allowed ABO-incompatible kidney transplantation to become an established routine at many centers across the world. Elderly represent a fast growing group both as organ donors and recipients. Besides age-related changes at organ level (i.e. glomerulosclerosis) ageing entails a complex and continuous remodeling of the immune system with aging. In this issue, Martins et al. reviews the distinctive features of handling an aging immune system in transplantation and provides insights into the immunosenescence processes in both transplant and nontransplant setting. The authors complete their review by discussing the clinical strategies currently being explored including optimal donor-recipient matching and several experimental immunomodulatory approaches that may provide starting points for additional tailoring and improvements. CD28, CTLA-4 and PD-L1, the three identified ligands for the B7 antigen receptors (CD80, CD86) are pivotal positive and negative costimulatory molecules controlling T cell mobility and the “immune synapse” between dendritic cells and T cells during alloimmune activation after organ transplantation [2]. Accumulating evidence from both experimental and clinical studies indicate that costimulation blockade using mainly monoclonal antibodies can lead to allospecific T-cell anergy and immune unresponsiveness. Envisioning the future, in this issue, Esposito et al. are reviewing the current knowledge on costimulation blockade and new therapeutic approaches aiming to modulate this signaling pathway toward immune tolerance, in the context of kidney transplantation. Induced CD4+ CD25+ FoxP3+ T-regulatory cells (iTregs) have been extensively proved to attain critical roles in immune activation after solid organ transplantation [3]. Within this process, IFNg holds key functions in both induction of Tregs as well as modulation of their immunosuppressive activity. Here, Daniel et al. are reviewing the actual knowledge on IFNg+ Tregs and provide new evidence regarding a distinct subset of IFNg-producing iTregs evaluating their potential as diagnostic (e.g. clinical rejection predictors) as well as therapeutic targets in organ transplantation. The results of clinical intestinal transplantation have continuously improved over the last decade due to several factors including new immunosuppressive strategies aiming at immune modulation rather than immune suppression [4]. Despite normally being the site oral tolerance, the intestine is far from achieving transplantation tolerance itself due to the several causes including the abundant donor-derived lymphoid tissue or the presence of HLA class II on the enterocytes. Meyer et al. provides a comprehensive review of the experimental approaches and clinical trials increasing the knowledge on mechanisms and strategies that favor the establishment of intestinal tolerance towards foreign antigens. An advanced preservation injury of the intestine may favor life threatening infectious complications due to the loss of the mucosal barrier and subsequent bacterial translocation. Moreover, an advanced ischemic injury may release danger signals that may further amplify the immune response toward the graft. In the last review of this issue, Drs. Oltean and Churchill summarize the current knowledge on intestinal preservation injury and briefly review the intestinal cold storage strategies. focusing on luminal preservation strategies as superior and feasible additional alternatives. The authors advocate for this approach with great translational potential and detail several alternative solutions that may be considered in future clinical trials.
International Reviews of Immunology
Transplant Immunology and Transplant Biology
Declaration of Interest The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.
Int Rev Immunol Downloaded from informahealthcare.com by Kainan University on 04/20/15 For personal use only.
REFERENCES [1] Meier-Kriesche HU, Kaplan B. Waiting time on dialysis as the strongest modifiable risk factor for renal transplant outcomes—a paired donor kidney analysis. Transplantation 2002;74:1377–1381. [2] Dilek N, Poirier N, Hulin P, et al. Targeting CD28, CTLA-4 and PD-L1 costimulation differentially controls immune synapses and function of human regulatory and conventional T-cells. PLoS One 2013;8(12): e83139. [3] Juvet SC, Whatcott AG, Bushell AR, Wood KJ. Harnessing regulatory T cells for clinical use in transplantation: the end of the beginning. Am J Transplant 2014;14:750–763. [4] Abu-Elmagd KM, Costa G, Bond GJ, et al. Five hundred intestinal and multivisceral transplantations at a single center: major advances with new challenges. Ann Surg 2009;250:567–581.
C Informa Healthcare USA, Inc. Copyright
