Centrum für Chronische Immundefizienz - CCI

Animal models for hemophagocytic lymphohistiocytosis (HLH), a defect in cytotoxicity of T cells and NK cells

Familial hemophagocytic lymphohistiocytosis (FHL) is a life-threatening primary immunodeficiency which is fatal without treatment. The disease is characterised by a severe disturbance of the immune homeostasis. Most cases of FHL are due to genetic defects in Perforin or in other genes involved in cellular cytotoxicity by NK cells or cytotoxic T cells. The hemophagocytic syndrome (HLH) can develop in the context of infections. The pathogenesis of this disease remains poorly understood. However, this is an important prerequisite for development of targeted immunological therapies. In this interdisciplinary project we want to further characterize the pathogenesis of FHL in animal models.

CV

Research Areas

1. Identification of initial triggers required for induction of HLH in FHL mice.

2. Impact of various genetic defects on HLH progression – correlation of genotype with phenotype.

3. Analysis of other immunological functions beside cytotoxicity of HLH related genes (SFB1160, project B04).
https://www.sfb1160.uni-freiburg.de/research/projects/b4/

4. Impact of T cell exhaustion on HLH pathogenesis.

5. Therapeutic intervention strategies in HLH:

• Adoptive T cell therapy
• Gene therapy (in collaboration with Prof. T. Cathomen, SFB1160, project A07) --> https://www.sfb1160.uni-freiburg.de/research/projects/a7/
• Modulation of activating and inhibitory receptors

Cooperations

• Yenan Bryceson, Karolinska Institute, Stockholm, Sweden
• Toni Cathomen, Institute for Transfusion Medicine and Gene Therapy, Freiburg
• Susana Minguet, Institute of Biology III, Freiburg
• Hanspeter Pircher, Max Planck Institute of Immunobiology and Epigenetics, Freiburg
• Marta Rizzi, Department of Rheumatology and Clinical Immunology, Freiburg
• Udo zur Stadt, Pädiatrische Hämatologie und Onkologie, Uniklinik Hamburg-Eppendorf

Publications

https://pubmed.ncbi.nlm.nih.gov/?term=Aichele+P%5BAuthor%5D

Team members