Clinical aspects of T-cell ageing in end-stage renal disease patients

Patients need to use immunosuppressive agents after renal transplantation which has disadvantages. Immunosuppressive drugs will reduce the risk for rejection, but on the other hand will increase the risk for diabetes, hypertension, infections, and they can even be harmful for the renal allograft because of their nephrotoxicity (51, 52). Since ESRD patients show a prematurely aged, circulatory T-cell immune system (11, 12), the use of these agents will impair their immune system even more. Therefore, definition of predictive T-cell parameters with regard to the development of rejection and infection is needed for a more personalized immunosuppression. Next to this, the ageing-related changes in circulatory T cells need to be compared with the changes in lymph nodes, since immune responses are initiated within lymph nodes. Thus, the objective of this thesis is, to evaluate the predictive value of T-cell ageing parameters and clinical outcomes such as the development of rejection and infection, and also to compare the changes in circulatory T cells with changes in the lymph nodes.

Chapter 1 will introduce the premature ageing process in ESRD patients and the different T-cell ageing parameters that can be assessed from the blood and lymph nodes.
Chapter 2 will discuss the relationship between circulatory T-cell ageing parameters assessed prior to renal transplantation and the development of acute allograft rejection within three months after renal transplantation.
Chapter 3 will describe the alloreactive potential of CD4+CD28null T cells, as these cells were associated with a reduced risk for rejection after renal transplantation.
Chapter 4 will assess the relationship between circulatory T-cell ageing parameters and the development of opportunistic and serious infections after renal transplantation.
Chapter 5 will describe how ageing-related changes in circulatory T cells relate to changes in the T-cell composition of lymph nodes.
Chapter 6 will evaluate the relationship between the development of early acute rejection after renal transplantation and the T-cell composition of the lymph node prior to renal transplantation. Next to this the alloreactivity of T cells isolated from lymph nodes and peripheral blood were also evaluated and compared. Chapter 7 will summarize and discuss all the obtained results
Chapter 8 will show a Dutch summary of the acquired results