Meanwhile intestinal transplantation (ITx) has become an established method for the therapy of severe intricasies in patients with short bowel syndrome. Intestinal transplantation is confronted with several problems that are similar to those of transplantations of other visceral organs, but that are much more distinct. For example the short bowel is characterised by a very low tolerance to ischemia. Chemokines, like TNF-α, play a major role in mediating I/R injury. The regulation of transcription is effected by nuclear factor κB (NF-κB). Until now in the context of ITx, TNF-α inhibitors have only been examined in the therapy of rejection and of chronic graft deterioration. The investigation of their efficacy in the modulation of I/R injury is the intention of this project.

As a consequence of the growing organ shortage, increased numbers of so called "Extended Criteria Donor" (ECD) grafts are utilized for transplantation. Various donor criteria including co-morbid disease, intensive care treatment, brain death, organ harvesting and prolonged ischemia have been identified as relevant risk factors. Additionally, increased donor and recipient age have been shown as independent risk factors for the development of chronic graft dysfunction. In experimental studies we observed an increased immunogenicity of the graft with increasing donor age as well as an augmenting memory T cell- and inflammatory immune response with increasing recipient age associated with an accelerated chronic graft deterioration. Those observations may have consequences on current clinical immunosuppression regimens and organ allocation.
In current rat kidney transplantation models, we dissect the effects of donor age on graft immunogenicity and consecutive alterations of the recipient´s immune response.

The induction of immunological graft tolerance without a lifelong immunosuppression represents the major goal in transplantation. Several strategies of tolerance induction targeting distinct pathways of T-cell activation have been developed in experimental models. However, experimental tolerance protocols have been almost exclusively tested in optimal individuals receiving organs from optimal donors. By contrast, in the clinical situation increased numbers of ECD grafts (extended criteria donor) are utilized to face the growing organ shortage, hazarding the consequences of various risk factors like co-morbid disease, intensive care treatment, brain death, increased donor and recipient age, and prolonged cold ischemia.
In current experimental studies we investigate the influence of donor and recipient age, and the effect of extended cold ischemia on tolerance induction protocols. Those data might be relevant when designing clinical tolerance protocols.

Kidney grafts from older donors demonstrate an increased incidence of acute rejection episodes leading to subsequent chronic graft deterioration. Clinical and experimental studies suggest that grafts from older donors are more immunogenic and therefore recipients of aged kidneys may require a more intense immunosuppression in the early period after transplantation.
Donor treatment may be particularly beneficial in older grafts. It has been shown that donor or graft treatment can induce protective genes and modulate the migration of dendritic cells. Own recent studies revealed reduced numbers of intragraft and peripheral dendritic cells following donor treatment with Cobalt Protoporphyrin (CoPP) or Methylene Chloride (MC) for the induction of HO-1 and CO, respectively. Others report on inhibitory effects of corticosteroids on the maturation and function of antigen presenting cells (APC).
In a current clinical study of the European Senior Program (ESP) we investigate the influence of steroid donor therapy on the long-term function of grafts from older donors and the immune response in the elderly recipient.

Beside good surgical skills, a study of experimental organ transplantation requires functional, immunohistological and histological examination of grafts as well as analysis of the recipients immunologic system. Routine histology (H&E staining) and immunohistochemistry (APAAP and AEC Techniques) are performed mostly on transplanted tissues (kidney, intestine), native organ resections (lungs, livers) and biopsies. Post-transplant immunologic monitoring focuses on leukocyte activity and cytokine production (ELISA) in recipient organs including blood, lymph nodes, graft tissue and spleen. The frequency of alloreactive lymphocytes is determined by Elispot. Screening of different populations of leukocytes, antigen presenting cells (APC) and adhesion molecules are assessed by flow cytometry (FACS).