Abstract
Organ transplants have been a life-saving form of treatment for many patients who are facing end stage organ failure due to conditions such as diabetes, hypertension, various congenital diseases, idiopathic diseases, traumas, and other end-organ failure. While organ transplants have been monumental in treatment for these conditions, the ten year survival and long-term outcome for these patients is poor. After receiving the transplant, patients receive a multi-drug regimen of immunosuppressants. These drugs include cyclosporine, mTOR inhibitors, corticosteroids, and antibodies. Polyclonal antibodies, which inhibit the recipient’s B lymphocytes, and antibodies targeting host cytokine inhibitors which prevent activation of B cells by T cells. Use of these drugs suppresses the immune system and increases the risk of opportunistic pathogen infections, tumors, and further damage to the transplanted organs and vasculature. Many regulatory mechanisms are present in organs to prevent the development of autoimmune disease, and Tregs are central to these mechanisms. Tregs secrete suppressive cytokines such as IL-10, TGF-B, and IL-35 to suppress T cells. Additionally, Tregs can bind to target cells to induce cell cycle arrest and apoptosis and can inhibit induction of IL-2 mRNA in target T cells. Tregs also interact with CTLA-4 and CD80/CD86 on antigen presenting cells (APCs) to prevent their binding to CD28 present on T cells. Due to their various immunosuppressive capabilities, Tregs are being examined as a possible treatment for patients that receive organ transplants to minimize rejection and prevent the negative outcomes. Several studies in which participants were given Tregs after undergoing organ transplantations were reviewed to determine the efficacy and safety of using Tregs in solid organ transplantation to prevent adverse outcomes.
Highlights
Solid organ transplantation is the treatment of choice for many patients who face end-stage organ dysfunction (1)
The goal of our paper is to give an overview of clinical studies, completed and ongoing, that test the effectiveness of T regulatory cells (Tregs) in solid organ transplantation trials by examining their effects on chronic rejection, acute rejection, graft versus host disease, and other associated diseases
In a study from the National Institute of Allergy and Infectious Diseases (NIAID) a phase I/II trial is being conducted in order to see if it is safe for liver transplant recipients to receive a dose of donor alloantigen reactive Tregs, and if it’s possible for these patients to reduce or completely stop immunosuppressive medications normally taken after transplant
Summary
Solid organ transplantation is the treatment of choice for many patients who face end-stage organ dysfunction (1). Combining both FOXP3 and CD127 could be an effective way to give better identification for patients with operational tolerance after liver transplantation (9) Because of their immunosuppressive capabilities, Tregs have hypothesized to play a role in prevention of auto-immune diseases such as asthma, allergies, and acute and chronic graft rejection of organs (2). The goal of our paper is to give an overview of clinical studies, completed and ongoing, that test the effectiveness of Tregs in solid organ transplantation trials by examining their effects on chronic rejection, acute rejection, graft versus host disease, and other associated diseases These studies examined the safety of Tregs and a variety of infusion protocols, methods for extracting and expanding Tregs, and the ability to induce tolerance in patients without the use of immunosuppressive therapies. This study would be improved with a larger sample size with more variation in age of participants as well, as the patients’ ages ranged from only 39-63 years old
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