Immunogenetics and transplantation.

It is well recognized that allospecific T cell activation is required for rejection. However, the process of allospecific T cell activation is largely controllable with current agents. Accordingly, short-term outcomes in allotransplantation have uniformly improved, a testament to the importance of the T cell-centric view of current therapy; thus, the field’s attention has turned toward lagging long-term outcomes. The inexorable chronic graft destruction that continues to define clinical transplantation suggests that there are important aspects of alloimmunity that are un-mollified by simple T cell-directed immunosuppression. Indeed, in the past decade it has become clear that the full biological phenomenon collectively recognized as rejection incorporates an almost Gordian network of factors, both inflammatory and regulatory, that shape the phenotype of allorecognition. T cell responses, including the T cell dependent allograft response, are contextually determined by the state of innate immunity in which T cells interact with antigen. Organs utilized for transplantation are usually obtained from deceased donors by a surgical procedure and then placed into cold preservation solutions before surgery implantation into the recipient. Brain death, ischemia reperfusion, hypoxia and hemostasis related injuries dramatically influence the state of innate immunity within the transplant. Overall, each of these processes activates innate immunity into a pro-inflammatory mode that is known to promote tissue destructive forms of adaptive immunity. These pathways and cell types have been left largely untargeted, or at least under recognized, and it is these finer points of rejection that serve as the focus of this issue of Current Opinion in Immunology…

Duke Scholars

Author Allan Douglas Kirk Surgery, Abdominal Transplant Surgery