Human T cell Immunodeficiencies

Human T cell Immunodeficiencies2024-07-15T12:59:18+02:00

Professor Stephan Ehl

Professor, Head, Department of Pediatric Immunology, Center for Pediatrics
Director, Institute for Immunodeficiency, Center for Chronic Immunodeficiency (CCI)

Simone Schruhl (Assistant to S. Ehl)
T: +49 (0)761 270-77550
F: +49 (0)761 270-77744

Medical Center– University of Freiburg
Center for Pediatrics
Department of Pediatric Hematology and Oncology
Section for Pediatric Immunology
Mathildenstraße 1
79106 Freiburg

T cell immunity is important for the control of most infections. A successful T cell response involves antigen recognition, cellular activation and differentiation, rapid expansion and exertion of effector functions. These potent and highly dynamic processes must be tightly regulated in order to avoid inappropriate or uncontrolled inflammatory responses. Human genetic diseases provide a fascinating window to understand T cell immunity and its relevance for the control of infectious diseases as well as for diseases of immune dysregulation.


Team members: from left to right:

  • Christoph König (PhD student)
  • Laura Faletti (Post-Doc)
  • Stephan Ehl (Group leader)
  • Sarah Grün (PhD student)
  • Patrick Kury (PhD student)
  • Jasmin Mann (PhD student)
  • Jonathan (Master student)
  • Heike Ufheil (Scientific coordinator CRC1160)
  • Carla Castro (Post-Doc)
  • Anne Rensing-Ehl (Post-Doc)

Not pictured: Henrike Ritterbusch (Study nurse), Marco Fischer (Study physician), Annette Uhlmann (Clinical Study Coordinator), Gerhard Kindle (Registry Coordinator), Maria Elena Maccari (Junior Group Leader).

If you are interested in joining our research team as an MD or PhD student or as a post-doc, please contact Stephan Ehl ( with a short description of your research experience and interests.


We study three immunodeficiency states representing models for different aspects of T cell immunity:

  • Hemophagocytic Lymphohistiocytosis (HLH)
  • Profound Combined Immunodeficiencies (P-CID)
  • Autoimmune-lymphoproliferative primary immunodeficiencies (AL-PID)

Hemophagocytic lymphohistiocytosis (HLH) is one of the most dramatic and life-threatening human inflammatory diseases. Patients with HLH offer a unique opportunity to study the molecular regulation of lymphocyte cytotoxicity and intracellular vesicle trafficking. We characterize the uncontrolled T cell response in HLH to better understand the pathophysiological basis of the disease. Patients without a genetic diagnosis are evaluated by whole exome sequencing in search of novel genetic causes. We coordinate a world-wide international registry and a clinical study platform for experimental treatment studies on HLH (TREAT-HLH). We are using observations in human patients and in MUNC13 deficient mice to prepare gene therapy for human patients with FHL3.

Combined immunodeficiencies (CID) present with a wide range of infectious diseases and manifestations of impaired immune regulation such as autoimmunity. The common immunological abnormality is a gentic impairment of T cell immunity. The study of CID offers a unique opportunity to understand the limiting factors of protective T cell immunity. We approach this problem by the study of individual patients, patient cohorts and mouse models. A prospective clinical study has been initiated to better define the threshold when stem cell transplantation should be performed in affected patients. In the laboratory, we combine genome analysis with functional assays to elucidate novel genetic causes for CID. These findings are related to the particular clinical phenotypes to better understand infection control and immune regulation in humans. The overall goal is to understand how human T cell immunity works under limiting conditions

Benign lymphoproliferation and autoimmunity, in particular autoimmune cytopenia, is observed in a number of primary immunodeficiencies (AL-PID). The most prevalent disorder is autoimmune lymphoproliferative syndrome (ALPS), which is mostly associated with germline or somatic mutations in CD95. We investigate the pathophysiological basis of impaired T cell homeostasis in human ALPS by a combination of genetic, phenotypic and functional investigations. In the last years, we have contributed to the discovery of several new diseases associated with lymphoproliferation and autoimmunity. A number of these conditions affect signalling pathways and metabolic programming of T cells, offering interesting insights into human T cell biology and attractive options for novel therapies.


Complete list of publications:



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