At the laboratory we have a wide range of assays to monitor pathways of donor directed reactivity. These assays focus on unraveling the T and B cell mediated immune responses and to study the mode of action of (novel) immunosuppressive drugs with the aim to titrate the immunosuppressive burden on our patients in such a way that side-effects (infections, malignancies, cardiovascular events) are kept at a minimum while at the same time rejection processes are prevented.
For more information on transplantation immunology applications within the Rotterdam Transplantation Laboratory please contact:
C.C. Baan, Prof. PhD
The research group of Michiel Betjes and Nicolle Litjens focusses on a number of transplant immunology related topics:
Uremia-associated T cell ageing
Starting from 2004, our research group has studied circulating T cells in patients suffering from end-stage renal disease prior to kidney transplantation and after having received a kidney transplant. We have characterized T-cell defects associated with loss of renal function and continued to evaluate relevance of these aspects with respect to kidney transplantation. We were first to introduce the concept of premature T-cell ageing as a phenomenon associated with phenotypic as well as functional T-cell defects observed in these patients which correlated to clinical outcome. Further research in this area will focus on thymus function and the possible suppressor role of highly differentiated T cells in relation to acute and chronic rejection.
Alloreactive T-cell function and donor-specific hypo-responsiveness
Anti-donor T-cell reactivity decreases slowly in the years after kidney transplantation, a phenomenon referred to as donor-specific hypo-responsiveness. The mechanisms responsible for this are unclear and may involve deletion, active suppression by regulatory T cells or induction of anergy in, anti-donor specific T cells. As of 2019, we are unravelling mechanisms by which anti-donor specific T-cell hypo-responsiveness develops after kidney transplantation in relation to ageing. We have developed an assay to identify alloreactive T cells which allows for functional characterization at the single cell level by unbiased analysis of multi-parameter flow-cytometry, exhaustion markers and single cell RNA sequencing.
Intra-renal T cells and rejection and fibrosis of the transplanted kidney
Long-term survival of kidney transplants is compromised by chronic antibody-mediated rejection and/or progressive fibrosis. Different T cell subsets are known to be involved in chronic humoral rejection but recent work showed they could also promote intra-renal fibrosis. As of 2020, we started to identify graft-infiltrating T cells in renal biopsies and employed our expertise on advanced flow cytometry single cell approaches to characterize phenotypic as well as functional aspects of T cells present within the renal biopsy .
Our research was mainly funded by the Dutch Kidney foundation and resulted in close to 50 publications in peer reviewed high impact journals as well as 3 PhD theses.
We perform our research in close collaboration with different Departments within our academic center (Department of Immunology, Center for Biomics) as well as from other national (Amsterdam//Utrecht/Nijmegen)/international universities (Taiwan).
For more information please contact:
Dr. N.H.R. Litjens
Dr. M.G.H. Betjes