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. 1. Introduction Kidneys are one of the most frequently transplanted human organs, with approximately 10,000 kidney transplants being performed annually in the United States [1]. Regarding absolute numbers of kidney transplantations, Brazil ranks second among all countries, after the United States and ranks ninth per million inhabitants [2]. The Brazilian Unified National Health System (Sistema único de Saúde—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]. Recipients of successful transplants have higher quality of life, which is directly linked to the continuous normal graft function [5]. Over the past two decades, significant progress has been achieved in graft rates and patient survival rates after kidney transplantation [6]. Some studies show that the half-life of deceased and living related allografts has improved to 13.8 and 21.6 years, respectively [7], and that there is more than 95% of patient survival rate and more than 91% of organ survival rate in one year [1]. Allograft rejection occurs because the
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