Abstract
Kidneys are one of the most frequently transplanted human organs. Immunosuppressive agents may prevent or reverse most acute rejection episodes; however, the graft may still succumb to chronic rejection. The immunological response involved in the chronic rejection process depends on both innate and adaptive immune response. T lymphocytes have a pivotal role in chronic rejection in adaptive immune response. Meanwhile, we aim to present a general overview on the state-of-the-art knowledge of the strategies used for manipulating the lymphocyte activation mechanisms involved in allografts, with emphasis on T-lymphocyte costimulatory and coinhibitory molecules of the B7-CD28 superfamily. A deeper understanding of the structure and function of these molecules improves both the knowledge of the immune system itself and their potential action as rejection inducers or tolerance promoters. In this context, the central role played by CD28 family, especially the relationship between CD28 and CTLA-4, becomes an interesting target for the development of immune-based therapies aiming to increase the survival rate of allografts and to decrease autoimmune phenomena. Good results obtained by the recent development of abatacept and belatacept with potential clinical use aroused better expectations concerning the outcome of transplanted patients.
Highlights
Kidneys are one of the most frequently transplanted human organs, with approximately 10,000 kidney transplants being performed annually in the United States [1]
We aim to present a general overview on the state-of-the-art knowledge of the strategies used for manipulating the lymphocyte activation mechanisms involved in allografts, with emphasis on T-lymphocyte costimulatory and coinhibitory molecules of the B7-CD28 superfamily
The central role played by CD28 family, especially the relationship between CD28 and CTLA-4, becomes an interesting target for the development of immune-based therapies aiming to increase the survival rate of allografts and to decrease autoimmune phenomena
Summary
Kidneys are one of the most frequently transplanted human organs, with approximately 10,000 kidney transplants being performed annually in the United States [1]. The Brazilian Unified National Health System (Sistema Unico de Saude—SUS) pays for more than 95% of the transplants performed in the country [2], and it provides the necessary posttransplant medication and follow-up care, representing a growing demand upon public resources [3]. It may be the largest public transplant program worldwide [4]. As immunosuppressive agents have become more effective at controlling acute rejection, chronic rejection has emerged as one of the major problems in clinical practice This process leads to an inexorable loss of kidneys at the rate of approximately 5% to 7% per year [9, 10]. Lymphocytes seem to play a key role in the immune response of the graft, leading to tissue damages [17]
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