Chemokine-receptor Mediated Dendritic Cell and T-cell Recirculation in Heart Failure and Transplantation
Heart failure (HF) is a complex clinical syndrome characterized by immune activation in its chronic stages. By different forms of cardiac dysfunction, infiltration of failing human myocardium with effector leukocytes through low-grade inflammation, leads to deterioration of clinical condition to endstage HF. The only available permanent therapeutic option for patients with end-stage cardiac disease is heart transplantation (HTx). Allo-antigen dependent immune cell activation and recirculation determine graft outcome, with heart allograft rejection remaining a severe complication after HTx. For years the international transplantation community attempts to improve patient survival and prevent graft loss. In this context, identifying patients at high risk for rejection or even predicting acute cardiac rejection (AR) would be important, as appropriate adjustments in immunosuppressive regimens may avoid over-immunosuppression related complications after clinical HTx. In this thesis, we attempted to clarify the role of chemokines and chemokine receptors in leukocyte recirculation during end-stage HF and rejection after HTx. Trafficking of dendritic cell (DC) and T-cell subsets received our particular attention, because their interaction critically determines the type of immune reactivity elicited in chronic disease and transplantation. Chapter 1, provides a general introduction on the migratory routes followed by DCs and T-cells, based on chemokines and their receptors. Known chemotactic pathways of leukocyte activation and infiltration as well as their role in the pathogenesis of HF and heart allograft rejection are presented. A description of the objectives of our studies is also included.
|Promotor||Bogers, A.J.J.C. (Ad) , Weimar, W. (Willem)|
|Sponsor||Bogers, Prof. Dr. A.J.J.C. (promotor) , Weimar, Prof. Dr. W. (promotor)|
Athanassopoulos, P.. (2006, June 28). Chemokine-receptor Mediated Dendritic Cell and T-cell Recirculation in Heart Failure and Transplantation. Retrieved from http://hdl.handle.net/1765/7842