Project Details
KFO 146: Cell-mediated Suppression of Auto- and Alloreactive Immune Responses
Subject Area
Medicine
Term
from 2006 to 2013
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 18407128
The main role of the immune system is the protection of the host from microorganisms such as bacteria and viruses. Although the immune system has an elaborate system of checks and balances to ensure selftolerance, occasionally this system breaks down. When the immune system attacks host components causing pathological change, this is called autoimmunity.
Prominent examples include rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease resulting from an attack of immune cells against its own intestinal tissue.
Furthermore, transplanted organs such as kidney, heart, and liver can be recognised by the immune system as non-self and are attacked by immune cells and rejected. In the case of allogeneic bone marrow transplantation there is a complication called graft-versus-host disease (GvHD) in which donor T cells in the bone marrow graft go on the offensive and attack the host's tissues. However, it is well established, that the curative potential of allogeneic bone marrow transplantation is due to immunocompetent donor T cells inducing potent antineoplastic effects against host tumor cells. This reaction, which is termed graft-versus-leukemia (GVL) effect, is clinically effective against a number of different hematologic malignancies such as myeloid and lymphoid leukemias, lymphoma, and myeloma. GVL effects usually but not exclusively occur in association with GvHD.
The Clinical Research Group aims to develop new strategies for the treatment of autoimmune diseases and graft rejection. Almost all current therapeutic concepts in autoimmune diseases and graft rejection are based on the systemic suppression of immune functions and are not curative.
Merely the elimination of such cells and also cells controlling the secreting effector cells could be curative and induce true long-term remissions. The therapeutic concepts investigated in the Clinical Research Group are based on the specific suppression of pathogenic immune cells that induce and sustain autoimmune inflammation and graft rejection while protecting the immune response against microorganisms. The ultimate goal of this consortium will be the translation of new immunological insights into therapy.
Prominent examples include rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease resulting from an attack of immune cells against its own intestinal tissue.
Furthermore, transplanted organs such as kidney, heart, and liver can be recognised by the immune system as non-self and are attacked by immune cells and rejected. In the case of allogeneic bone marrow transplantation there is a complication called graft-versus-host disease (GvHD) in which donor T cells in the bone marrow graft go on the offensive and attack the host's tissues. However, it is well established, that the curative potential of allogeneic bone marrow transplantation is due to immunocompetent donor T cells inducing potent antineoplastic effects against host tumor cells. This reaction, which is termed graft-versus-leukemia (GVL) effect, is clinically effective against a number of different hematologic malignancies such as myeloid and lymphoid leukemias, lymphoma, and myeloma. GVL effects usually but not exclusively occur in association with GvHD.
The Clinical Research Group aims to develop new strategies for the treatment of autoimmune diseases and graft rejection. Almost all current therapeutic concepts in autoimmune diseases and graft rejection are based on the systemic suppression of immune functions and are not curative.
Merely the elimination of such cells and also cells controlling the secreting effector cells could be curative and induce true long-term remissions. The therapeutic concepts investigated in the Clinical Research Group are based on the specific suppression of pathogenic immune cells that induce and sustain autoimmune inflammation and graft rejection while protecting the immune response against microorganisms. The ultimate goal of this consortium will be the translation of new immunological insights into therapy.
DFG Programme
Clinical Research Units
Projects
- Antigen-spezifische Elimination von primären CD4+ und CD8+ T-Zellen durch Apoptose-induzierende artifizielle antigenpräsentierende Zellen in vitro (Applicant Fleck, Martin )
- Basophile Granulozyten als neue Regulatoren einer GvHD und GvT Reaktion (Applicant Mack, Matthias )
- Einfluss CD4+CD25+ regulatorischer Spender T-Zellen auf die Infektabwehr nach allogener Stammzelltransplantation (Applicant Hoffmann, Petra )
- Epigenetik zelltypspezifischer Genexpression in T-Zell-Subpopulationen (Applicant Rehli, Michael )
- Immunregulation durch adoptiven Transfer humaner CD4+CD25+ regulatorischer T-Zellen im xenogenen GVHD-Modell (Applicant Edinger, Matthias )
- Immunregulatorische Funktionen humaner TCRáâ+ CD4-CD8- doppelt negativer T-Zellen (Applicant Mackensen, Andreas )
- Untersuchung der Bedeutung von CpG Motiven bakterieller DNA für die Homöostase des intestinalen Immunsystems (Applicant Obermeier, Florian )
- Use of Monocyte-Derived Cells to Control Autoimmune Reactions in Patients with Chronic Inflammatory Bowel Disease (Applicant Geissler, Ph.D., Edward K. )
- Zell-vermittelte Suppression von auto- und alloreaktiven Immunreaktionen (Z-Projekt) (Applicant Edinger, Matthias )
Spokesperson
Professor Dr. Reinhard Andreesen