The role of ICOS for T follicular helper responses

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The specialised subpopulation of T follicular helper cells (TFH) is of central importance for the humoral immune response. Without TFH cells no high affinity antibodies or long-lived plasma cells are generated. Therefore, TFH cells are also a promising target for therapeutic intervention in autoimmune diseases. With the inducible costimulator ICOS we have identified a key regulator of TFH generation and/or maintenance. With the help of a murine in vivo T/B cooperation system which is based on the adoptive transfer of antigen-specific T and B cells into immunocompetent mice we want to investigate the underlying molecular mechanisms. In a first part of the project we will use flow cytometry, immunohistology, and two-photon in vivo imaging to analyse how missing or interrupted ICOS costimulation affects the fate of antigen-specific T and B cells. In particular we are interested in the dynamics of T/B cooperation within the germinal centre. In a second part we want to re-isolate antigen-specific TFH cells after ICOS in vivo blockade and analyse their transcriptome. Using a retroviral expression system we will test the functional relevance of ICOS regulated genes for TFH development and function.