Kurzfassung

For many patients with hematologic diseases allogeneic stem cell transplantation (aSCT) is the only curative therapy option. After aSCT, Graft-versus-Host-disease (GvHD) is a common complication with high morbidity and mortality. Current state-of-the-art therapy of GvHD leads to a general immune suppression that extenuates the required Graft-versus-leukemia-effect.
In our research group we try to suppress GvHD with naturally occurring regulatory T-cells (Treg), with the aim of creating new...For many patients with hematologic diseases allogeneic stem cell transplantation (aSCT) is the only curative therapy option. After aSCT, Graft-versus-Host-disease (GvHD) is a common complication with high morbidity and mortality. Current state-of-the-art therapy of GvHD leads to a general immune suppression that extenuates the required Graft-versus-leukemia-effect.
In our research group we try to suppress GvHD with naturally occurring regulatory T-cells (Treg), with the aim of creating new therapeutic strategies without causing a general immune suppression after aSCT. In former murine models an anti-GvHD-effect after treatment with Treg could be shown, but the role of Treg in pathophysiology and treatment of GvHD especially in humans remains unclear.
In this project will try to elucidate how far GvHD prophylaxis in the conditioning regimes before aSCT like Anti-Thymozytenglobulin (ATG), anti-CD52-antibody Alemtuzumab and Calcineurin-inhibitors such as Cyclosporin A, Tacrolimus or Mycofenolat Mofetil after aSCT influences reconstitution of Treg.
To figure out what could be the most effective point of time for a Treg therapy after aSCT we will investigate whether patient Treg are able to suppress effector T cells and whether patient effector T cells are susceptible to Treg-inhibition ex vivo at different time points after aSCT.
In a third step we plan to identify potential biomarkers in Treg via Next-Generation-Sequencing based transcriptome analyses which could give information about function and potential of Treg activation at molecular levels to predict which patients would profit from Treg-DLI.
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