Genetic diseases provide a fascinating window to understand human T cell immunity and its relevance for the control of infectious diseases and immune homeostasis. Our group works at the interface between clinical and basic immunology and integrates both physicians and basic scientists. Our translational research activities start with observations in patients with genetic alterations affecting T cell development and function. Molecular and functional analysis of T cells from these patients help to uncover the relevance of these genes for immune function. Cellular and animal models are used to better understand disease pathogenesis and to evaluate novel treatment options.
We study three immunodeficiency states representing models for different aspects of human T cell immunity:
Combined immunodeficiencies (CID), caused by genetic defects affecting T cell development and activation. We focus on defects allowing residual T cell development to define the minimum level T cell immunity required for a healthy life.
Autoimmune-lymphoproliferative primary immunodeficiencies (AL-PID), most frequently caused by signalling defects in the Fas and JAK/STAT pathways. We use these diseases to understand the molecular and metabolic control of T cell homeostasis.
Hemophagocytic lymphohistiocytosis (HLH), caused by genetic defects of lymphocyte cytotoxicity. We study the molecular regulation of T cell cytotoxicity and the inflammatory consequences of its failure.