Mahyar Nouri-Shirazi
Abstract
Dendritic cells (DCs) are a heterogeneous family of professional APCs involved in priming adaptive immune responses. Donor DCs (direct pathway of allorecognition) and recipient DCs presenting processed donor major histocompatibility complex (MHC) as peptides (indirect pathway of allorecognition) participate ...
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Dendritic cells (DCs) are a heterogeneous family of professional APCs involved in priming adaptive immune responses. Donor DCs (direct pathway of allorecognition) and recipient DCs presenting processed donor major histocompatibility complex (MHC) as peptides (indirect pathway of allorecognition) participate actively in graft rejection by stimulating recipient T cell responses following organ transplantation. Recent studies have shown that DCs also play a central role in inducing and maintaining tolerance to self antigens (Ags) through deletion, anergy, and regulation mechanisms. It is easy to see how the remarkable functional plasticity of DCs renders them attractive therapeutic targets for immune modulation. Indeed, in the past few years, successful outcomes in rodent models have built the case that DC-based therapy may provide a novel approach to transplant tolerance. Ongoing research into our understanding of the mechanisms whereby DCs promote tolerance in the steady-state, together with development of biologi-cally, pharmacologically and genetically manipulated ex vivo DCs to mimic/enhance their natural tolerogenicity, should warrant the success of these experimental DCs in establishing long-term allograft survival.
Amir Hassan Zarnani; Pouneh Dokouhaki; Mahmood Jeddi-Tehrani
Abstract
Indoleamine 2,3-dioxygenase (IDO), an enzyme involved in the catabolism of tryptophan, is expressed by a variety of cells and tissues such as macrophages, dendritic cells, cells of the endocrine system and by the placenta. IFN- γ is the main inducer of this enzyme. IDO acts as an important defense ...
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Indoleamine 2,3-dioxygenase (IDO), an enzyme involved in the catabolism of tryptophan, is expressed by a variety of cells and tissues such as macrophages, dendritic cells, cells of the endocrine system and by the placenta. IFN- γ is the main inducer of this enzyme. IDO acts as an important defense mechanism of innate immunity against pathogens. It also has tumor suppressive activity and prolongs the survival of allograft. One of the interesting functions of IDO is prevention of the allogenic fetus rejection during pregnancy by inhibiting alloreactive T cells. It was shown that inhibition of IDO activity by IDO inhibitor, 1-methyl tryptophan, during mouse pregnancy causes fetal rejection. The main mechanism by which IDO protects fetus is through reducing the tryptophan level and suppressing the T cell activity in the feto-maternal interface. In this review the biological functions of IDO with emphasis on its role in allogeneic fetus protection have been discussed.
Nasrollah Ghahramani
Abstract
The subject of transplant immunosuppression has generated significant interest in recent years. Excellent immunosuppression, advances in surgical technique, post-transplantation care, and infection control have resulted in excellent outcomes. There is widespread support for the notion that the fundamental ...
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The subject of transplant immunosuppression has generated significant interest in recent years. Excellent immunosuppression, advances in surgical technique, post-transplantation care, and infection control have resulted in excellent outcomes. There is widespread support for the notion that the fundamental objective in transplant immunology should be the achievement of specific graft tolerance. However, until this objective evolves into reality, investigators are in search of the “ideal immunosuppressant”, which should target predominantly the immune system with minimal consequences for other tissues and minimal metabolic, cardiovascular and renal complications. While immunosuppressants have been associated with a tremendous trade-off in terms of morbidity, new agents have provided the investigators with the opportunity to formulate strategies that employ combination therapies with the goal of decreasing doses of individual agents and minimizing their toxicities. Multiple small studies have addressed the issue of minimizing immunosuppressants, but there is a need for well-designed clinical trials which should evaluate protocols that will reduce acute rejection, as well as chronic allograft nephropathy. They should address methods to identify subsets of patients who would maximally benefit from avoidance or withdrawal of steroids or calcineurin inhibitors. Other promising areas of research include tolerance studies among the sensitized recipients, and development of optimal immunosuppression based on genotype. In general, future trials must include a more diverse population of recipients, particularly the immunologically high risk groups.
