Visual Universitätsmedizin Mainz

Research Team Dr. Jonuleit

Team Jonuleit

Head:

HD Dr. rer. nat. Jonuleit
Helmut Jonuleit, HD Dr. rer. nat.

+49 (0)6131-172957
+49 (0)6131-17473541

Team:

Dr. Andrea Tüttenberg, wissenschaftliche Assistentin
Dr. Jan Kubach, Postdoc
Anita Correll, Doktorandin
Bettina Trinschek, Doktorandin
Mohamed Hossam El-Din, Doktorand
Mario Hubo, Doktorand
Andreas Sommer, Doktorand
Ayten Balli, MTA
Lydia Paragnik, MTA

Major Research Interests:

The mayor interests of the group are the functional characterization of human dendritic cells and regulatory T cells, development of efficient dendritic cell-based cellular therapies of cancer, T cell modulatory components for treatment of imbalanced immune responses in allergy, autoimmunity and chronic inflammatory diseases and cancer.

Current Funding:

SFB-548: "Analysis and modulation of allergic and autoimmune diseases", Subpoject A8: "Functional characterization of human regulatory T cells"

CD4+CD25+ regulatory T cells (CD25+ Tregs) play a central role in the induction and maintenance of peripheral tolerance. They suppress the activation of autoaggressive CD4+ and CD8+ T cells. In the last years we were able to characterize different human CD25+ Treg subsets. We have shown that naïve CD4+ T cells differentiate after repetitive stimulation with immature dendritic cells (DC) into IL-10-producing Tregs, which suppress the activation of conventional T cells. Furthermore, we identified two functional distinct subsets of human CD25+ Tregs in the peripheral blood characterized by the expression of different surface integrins (α4β7+ and α4β1+ CD25+ Tregs). Both subsets are anergic and inhibit proliferation and cytokine release of conventional T cells in a contact-dependent manner. Additionally, they transfer suppressive activity to co-cultured CD4+ T helper cells by a mechanism called infectious tolerance.
Aim of this project is the identification and functional characterization of Treg-specific proteins, responsible for the functional properties of human Tregs.

SFB-432: "Mechanisms of tumor defense and their therapeutic implications", Subproject B11: "Analysis and modulation of immune suppression by regulatory T cells and dendritic cells in melanoma patients"

Dendritic cells (DC) are specialized for the initiation of T cell immunity, including cytotoxic T cells (CTL), which kill virus infected as well as malignant cells. In mouse models, immunization with antigen pulsed or transfected DC efficiently primes CD4+ and CD8+ T cells, resulting in protective immunity against infectious agents and tumors. Because of their unique properties as professional antigen-presenting cells to induce protective immune responses, several strategies using tumor antigen-loaded DC as “natural adjuvants” for immunotherapy of cancer patients were developed. Numerous preclinical and clinical studies using in vitro-generated monocyte-derived DC in combination with tumor-associated antigens for the treatment of patients with advanced (stage IV) melanoma were implemented. However, in most cases the immune system of advanced stage IV cancer patients allows only a transient anti-tumor response. Moreover, increasing evidence exists that active suppression by anergic conventional T cells, tumorantigen-specific Tregs and tolerogenic DC ultimately prevent "autoaggressive" immune reactions against the tumor.

The abrogation of the suppressive influence of Tregs on anti-tumor immune responses is certainly of vital importance for future anti-cancer vaccine strategies. Aims of this project are the functional characterization of CD25+ Tregs in melanoma patients in different stages of disease and to design protocols for transient manipulation of these suppressors. Additionally, we will develop novel protocols for generation of "conditioned" DC for an efficient DC-based immunotherapy of melanoma patients. Conditioning of mature DC by certain signals, such as TLR ligands, should allow these DC to overcome suppressive Treg-activity for tumor antigens. Thereby, self-tolerance might be broken and effective anti-tumor T cell responses should be induced.
A better understanding of interactions between DC, different members of the Treg family and other cells of the immune system will lead to improved protocols for clinical use of defined DC for the induction of efficient immune responses against cancer.

European Union & NRW: "Applications of proteomics for identification of targets for therapeutic uses by proteomics and biomarker identification for diagnostics by proteomics"

In this project we analyze and compare the proteomes of freshly isolated and activated human CD4+ T cells and CD25+ regulatory T cells (CD25+ Tregs). Goal of this study is the identification and functional characterization of Treg-specific proteins. Therefore, large amounts of different T cell subsets will be isolated from distinct blood products and afterwards proteomes of T cell subsets will be analyzed in cooperation with Protagen AG in Dortmund. The first Treg-specific proteins have been identified and functionally characterized.

Research cooperation with Boehringer-Ingelheim GmbH: "Immunomodulation with regulatory T cells and dendritic cells"

In this project we isolate different T cell populations for generation of monoclonal antibodies specific for human regulatory T cells (Tregs). Goal of this study is the generation and characterization of Treg-specific antibodies for therapeutic uses.