Heart transplantation has become a rapidly evolving therapy for end-stage heart failure. To reduce the risk of rejection of the transplanted organ, patients are treated with immunosuppressive therapy. However, as immunosuppressive drugs carry severe side effects, true transplant tolerance (i.e., long-lasting nonreactivity of the immune system to donor antigens in the absence of immunosuppressive drugs) is a major goal in transplantation research. T-cell-mediated regulation of donor-reactive cells is one of the mechanisms that may be involved in the induction and maintenance of graft acceptance after organ transplantation. The identification and characterization of regulatory T cells that can control the anti-donor immune reactivity has therefore become the focus of many studies. Research in experimental transplant models has demonstrated that these regulators are important for the prevention of allograft rejection and the induction of transplant tolerance.1! -4 Yet, it remains to be elucidated whether regulatory T cells control anti-donor immune reactivity in immunosuppressed organ transplant patients, thereby inducing and maintaining donor-specific nonresponsiveness. The central aim of this thesis was to investigate the role of regulatory T cells in the control of immune responses directed to the transplanted graft of heart transplant patients. We focused on two compartments where functional regulatory T cells may be present, i.e. the transplanted heart and the peripheral blood. Our studies demonstrated that various regulatory T-cell populations present in these compartments play a role in immunological processes, such as immunological quiescence and acute cellular rejection.

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Netherlands Heart Foundation, Dutch Transplantation Society, Astellas Pharma B.V., Novartis Pharma B.V., Roche Nederland B.V., Genzyme Europe B.V., Bristol-Myers Squibb B.V.
Erasmus MC: University Medical Center Rotterdam
W. Weimar (Willem)
Erasmus MC: University Medical Center Rotterdam

Dijke, E. (2009, January 14). Immune Regulation after Heart Transplantation: Dynamics of regulatory T cells in the transplanted heart and peripheral blood. Retrieved from http://hdl.handle.net/1765/16010