Lymphoproliferative disease resulting from impaired deletion of FAS controlled T cells. (A08*)

• Subject Area: Rheumatology
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 256073931

This project will study autoimmune-lymphoproliferative syndrome (ALPS) as a model of uncontrolled lymphoproliferation, caused by FAS deficiency. The goal is to delineate the ontogeny, specificity, induction and differentiation of FAS controlled (FC) T cells. They hypothesize that any post-thymic T cell can acquire the specific FC T cell differentiation program, provided it receives the appropriate signals in the right environment. Human CyTOF based developmental modelling will be combined with scRNAseq and TCR sequence analysis for a more precise delineation of cell transitions from naïve towards the program of FC T cells. Based on the hypothesis that FC T cell fate is induced in secondary lymphoid organs, the microanatomical localization, cellular interactions partners and ligand/receptor pair expression of FC T cells and interacting immune cells in lymph node tissue will be determined using immunohistochemistry, imaging mass cytometry and spatial multiomics. The generated hypothesis on FC T cell ontogeny and fate induction will be tested by competitive adoptive transfer and infection experiments in Fas-deficient lprcg mice.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1160: Immune-mediated pathology as a consequence of impaired immune reactions (IMPATH)
• Applicant Institution: Albert-Ludwigs-Universität Freiburg
• Project Heads: Dr. Maria Elena Maccari; Dr. Anne Katharina Rensing-Ehl