ten Berge R.J.M.: Transplantation Immunology

Project Details


(1) Development of antiviral immune responses and their interplay with allo-immune responses after renal transplantation. Studies on the immune response against CMV will be continued and will focus on heterogeneity of the T cell response using new generation sequencing (NGS) techniques. Studies in peripheral blood will be extended to other lymphoid compartments and the allograft itself. Next, we will characterize the interplay between adaptive immune responses to viral - and allo-antigens with emphasis on the role of heterologous (cross-reactive) immunity.
(2) Study on the development of cellular immunity against BK-Virus. Using different HLA-A02-tetramers, we developed methods to characterize circulating BKV-specific CD8+ T cells, essential in the defence against the virus. Phenotypic analysis showed that BKV-specific T cells in healthy individuals are mainly VP1-specific and can be considered as non-activated ‘effector memory’ T cells that express granzyme-K, but no other cytotoxic molecules. Next, these cells will be studied in immunocompromised renal transplant recipients, suffering from BKV nephropathy, which is an important cause of renal transplant morbidity and graft loss.
(3) We previously showed that BKV-viremia is associated with induction of TLR3, MDA5, and RIG-I in tubular epithelium and that these dsRNA-sensors trigger an anti-viral and pro-apoptotic program in primary human tubular epithelial cells. Next, we aim to clarify the recognition of - and overall innate immune response against BKV, and to elucidate immunoevasive strategies of the virus. In addition, we will identify factors that facilitate viral (re)activation in renal epithelium and contribute to the development of BKV-nephropathy.
(4) Optimization of immunosuppressive drug therapy in renal transplantation. As part of a new recently started clinical trial, immunological, vascular and pharmacological studies will be performed.
Effective start/end date1/01/2006 → …