The existence of T-cell subsets naturally committed to perform immunoregulation has led to enthusiastic efforts to investigate their role in the immunopathogenesis of transplantation. Being able to modulate alloresponses, regulatory T cells could be used as an immunodiagnostic tool in clinical kidney transplantation. Thus, the measurement of Foxp3 transcripts, the presence of regulatory T cells in kidney biopsies, and the phenotypic characterisation of the T-cell infiltrate could aid in the diagnosis of rejection and the immune monitoring and prediction of outcomes in kidney transplantation. Interestingly, the adoptive transfer of regulatory T cells in animal models has been proven to downmodulate powerful alloresponses, igniting translational research on their potential use as an immunomodulatory therapy. For busy transplant clinicians, the vast amount of information in the literature on regulatory T cells can be overwhelming. This paper aims to highlight the most applicable research findings on the use of regulatory T cells in the immune diagnosis and potential immunomodulatory therapy of kidney transplant patients. However, can we yet rely on differential regulatory T-cell profiles for the identification of rejection or to tailor patient's immunosuppression? Are we ready to administer regulatory T cells as inductive or adjunctive therapy for kidney transplantation? 1. Introduction The avoidance of long-term immunosuppression by achieving immunological tolerance would be the ultimate solution to improving long-term patient survival and giving kidney transplant patients a better quality of life. Unfortunately, owing to its complex immunopathogenesis, true immunological tolerance to avert alloresponses has been difficult to achieve. In particular, once the alloresponse is established, it is extremely difficult to control because of its strong and self-amplifying effector mechanisms. These obstacles form the platform of unceasing battles against transplant rejection. Amongst the mechanisms implicated in the generation and/or maintenance of immune tolerance, the immunoregulatory role of regulatory T cells (Tregs) is one of the most attractive yet elusive one. In the early 1970s, seminal experiments by Gershon and Kondo [1, 2] unveiled the existence of a population of suppressor T cells, but subsequent failures to substantiate their theory had led to the demise of their idea for almost three decades [3, 4]. The interest in the suppressor T cell resurged in 1995 after Sakaguchi’s work, which elegantly demonstrated the existence of a subset of CD4+CD25+ T
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