Allo-specific immunosuppression by relatory T cells.
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KUN Katholieke Universiteit Nijmegen, 12 november 2004
Promotor : Pauw, B.E. de Co-promotor : Joosten, I.
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Blood Transfusion and Transplantation Immunology
SubjectUMCN 1.4: Immunotherapy, gene therapy and transplantation
Transplantation of an allogeneic donor organ results in recipient T cell activation. Under normal circumstances there is a balance between aggressive T cells and suppressive regulatory T cells. In case of transplantation especially the aggressive T cells will divide and initiate rejection. Nowadays, immunosuppressive drugs are used to inhibit T cell expansion, thereby preventing graft rejection. These drugs have many side effects and act in a non-antigen specific way, meaning that also desired T cell responses against pathogens are inhibited. Hence, it is crucial to develop donor specific immuno suppressive modalities. This might be established by therapeutic approaches that shift the balance between aggressive and suppressive regulatory T cell towards donor specific regulatory T cells. In our laboratory we focus on donor specific immunotherapy with ex vivo generated donor (alloantigen)-specific regulatory T cells. In this thesis, ex vivo generation and expansion protocols are described that result in donor antigen-specific regulatory T cells. These cells are of great importance for donor specific immunotherapy in transplantation and offer a route to permanent graft survival without the need for life-long non-specific immunosuppression.
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