SFB 633:  Induction and Modulation of T cell Mediated Immune Responses in the Gastrointestinal Tract

• Subject Area: Medicine
• Term: from 2003 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5485888

The special characteristics of the intestinal immune system make it a very suitable site to determine mechanisms of immunologic tolerance induction and then to use this knowledge for therapeutic application. In addition, many gastrointestinal diseases can serve as natural models of a disturbed balance between protective, proinflammatory and tolerogenic immune reactions, allowing deeper insight into regulatory mechanisms operating "in vivo".
This is relevant since the induction of a specific immune response through vaccination is one of the most important medical advancements of all times. However, specific modulation of unwanted immune responses, e.g. in autoimmune diseases and chronic inflammatory diseases, while safeguarding immune responses that are protective for the organism, is still hardly possible.
The prerequisites of specific immune modulation will be generated by the work done within the Collaborative Research Centre. As a long term goal, the Research Centre equally aims at the specific augmentation of wanted and the suppression of unwanted specific immune reactions.
Part A (Topography and Induction of Immune Reactions in the Gut) comprises projects which aim at a better understanding of the local interaction of antigen presenting cells and T cells during antigen specific immune reactions and the resulting activation and differentiation of mucosa associated T cells.
Projects in part B (Regulation and Modulation of Intestinal Immunity) focus on the characterisation of factors involved in local T cell differentiation and migration to the gastrointestinal mucosa. A better understanding of these factors, also in the context of destructive immune responses present in different models of inflammation, will allow to work out concepts to modulate abnormal T cell differentiation in inflammatory diseases. One important aspect of the work performed is to achieve results that are clinically relevant. For that reason, parallel to a spectrum of well defined animal models, studies in normal volunteers and patients are started from the beginning and immune responses are studied to soluble proteins, in infection and in intestinal tumors.

• DFG Programme: Collaborative Research Centres

Completed projects

• A001 - Analysis of the presentation of orally applied antigens and the specific T cell reaction: tolerance versus immunity (Project Heads Radbruch, Andreas ;  Scheffold, Alexander )
• A01 - Analysis of the presentation of orally applied antigens and the specific T cell reaction: tolerance versus immunity (Project Head Scheffold, Alexander )
• A02 - Charakterisierung humaner T-Zellantworten nach mukosaler Antigenexposition: Toleranzinduktion vs. Immunisierung (Project Heads Duchmann, Rainer ;  Zeitz, Martin )
• A03 - Untersuchungen zur Funktion intestinaler Immunzellen in humanen peyerschen Plaques und muskosalen Lymphfollikeln (Project Heads Ullrich, Reiner ;  Zeitz, Martin )
• A04 - Identification of T cell epitopes relevant for inflammatory bowel diseases and their rheumatic manifestations (Project Heads Duchmann, Rainer ;  Sieper, Joachim ;  Thiel, Andreas )
• A05 - Analysis of the spontaneous and induced immune response against tumors of the gastrointestinal tract (Project Heads Blankenstein, Thomas ;  Willimsky, Gerald )
• A06 - Mukosale antigen-spezifische T-Lymphozytenantwort im Verlauf einer bakteriellen Infektion (Project Heads Kaufmann, Stefan H.E. ;  Mittrücker, Hans-Willi )
• A07 - Microbiota-mediated regulation of intestinal T-cell responses (Project Heads Bereswill, Stefan ;  Göbel, Ulf B. ;  Schumann, Ralf Reiner )
• A08 - The liver as a part of the mucosal immune system: induction of oral tolerance and of regulatory CD4+ T cells (Project Head Klugewitz, Katja )
• A10 - Impact of CD8+ T-cell activation in the liver on the development of extraintestinal manifestations of inflammatory bowel diseases in the liver (Project Head Schott, Eckart )
• A12 - Mesenteric adipose tissue - regulatory function in intestinal inflammation (Project Head Siegmund, Britta )
• A13 - Significance of tumor necrosis factor and lymphotoxin signalling for mucosal immunity (Project Head Nedospasov, Sergei A. )
• A14 - Characterisation of human peripheral and intestinal T cell responses after mucosal antigen exposition: Induction of tolerance vs. immunity (Project Heads Dörner, Thomas ;  Ullrich, Reiner )
• A15 - Analysis of tolerance induction of interleukin-17-producing T helper cells in the small intestine (Project Heads Esplugues, Ph.D., Enric ;  Hauser, Anja Erika )
• B01 - Induction of specific homing receptors and of regulatory properties in mucosal T cells (Project Heads Hamann, Alf ;  Hühn, Jochen )
• B02 - Regulation of lmymphocyte effector/memory functions in the mucosal immune response (Project Heads Höpken, Uta Elisabeth ;  Lipp, Martin )
• B03 - Funktion von CD2 für die intestinale T-Zellaktivierung und deren Modulation bei Colitis (Project Head Hoffmann, Jörg Carl )
• B04 - Immunmodulatorische Funktion von CD44v7 bei der Induktion von antigenspezifischer Toleranz (Project Head Wittig, Bianca )
• B05 - Konsequenzen der darmspezifischen Zytokinsekretion auf die immunologische Homöostase, Infektabwehr und Entzündung (Project Head Kaufmann, Stefan H.E. )
• B06 - Mechanisms of induction and effector function in T-cell-mediated ileitis following oral infection with Toxoplasma gondii (Project Head Heimesaat, Markus M. )
• B07 - Analysis of proteasome mediated inflammation in patients with inflammatory bowel disease (Project Heads Kroesen, Anton Josef ;  Steinhoff, Ulrich )
• B09 - Morbus Whipple - Investigation of interactions of T cells and antigen-presenting cells (Project Heads Moos, Verena ;  Schneider, Thomas )
• B10 - The role of proinflammatory T cells in chronic mucosal inflammation (Project Heads Chang, Hyun-Dong ;  Radbruch, Andreas ;  Thiel, Andreas )
• B11 - Cellular approaches for the treatment of intestinal Graft-versus-Host disease and inflammatory bowel disease (Project Heads Maul, Jochen ;  Rieger, Kathrin ;  Uharek, Lutz )
• B12 - Modulation of the T cell dependent immune defence against Helicobacter pylori under the influence of cholesterol (Project Heads Aebischer, Anton ;  Ignatius, Ralf ;  Meyer, Thomas F. ;  Schneider, Thomas )
• B14 - Role and potential therapeutic use of interleukin-22+ Natural Killer cells in colitis (Project Head Romagnani, Ph.D., Chiara )
• B15 - Regulation of the intestinal homeostasis by interleukin-7 (Project Head Schüler, Thomas )
• E01 - Mechanisms of induction and effector function in T-cell-mediated ileitis following oral infection with Toxoplasma gondii (Project Head Heimesaat, Markus M. )
• MGK - Integrated Research Training Group IMMUCO (Project Heads Klugewitz, Katja ;  Moos, Verena ;  Radbruch, Andreas ;  Zeitz, Martin )
• Z01 - Development of systematic morpholgical methods for the evaluation of mucosal inflammations and the in-situ detection of defined cell populations (Project Heads Kühl, Anja A. ;  Schulzke, Jörg-Dieter ;  Siegmund, Britta ;  Zeitz, Martin )
• Z02 - Entwicklung und Durchführung von Technologien zur Antigen-spezifischen Zytomerie mittels Multiparamteranalyse (Project Head Scheffold, Alexander )
• Z02 - Administrative Project of the Collaborative Research Centre (Project Heads Siegmund, Britta ;  Zeitz, Martin )

• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Co-Applicant Institution: Freie Universität Berlin; Humboldt-Universität zu Berlin
• Participating Institution: Deutsches Rheuma-Forschungszentrum Berlin (DRFZ); Max-Delbrück-Centrum für Molekulare Medizin (MDC); Max-Planck-Institut für Infektionsbiologie; Robert Koch-Institut (RKI)
• Business and Industry: Miltenyi Biotec B.V. & Co.KG
• Spokespersons: Professorin Dr. Britta Siegmund, since 10/2012; Professor Dr. Martin Zeitz, until 9/2012 (†)