Adaptive Immunity Laboratory

Exploring tissue-specific CD8+ T cell biology during adaptive immune responses

The adaptive immune system protects us from harmful microbial infections and cancer, and provides life-long immunity after vaccination. To accomplish these extraordinary feats, cellular components of the immune system, T and B cells, continuously interact with antigen-presenting cells (APCs) in multiple organs. A well-studied example are naïve CD8⁺ T cells interactions with dendritic cells, the most powerful APCs for this subset. Their cross-talk results in CD8⁺ T cell activation, differentiation to cytotoxic effector cells and invasion of infected organs for elimination of virus-infected or tumorigenic cells. Following the acute immune response, memory CD8⁺ T cells patrol the body to protect from remerging pathogens.

The general principles of such adaptive immune responses are well established. Yet, little is known on how CD8⁺ T cell biology and microenvironmental cues - tissue-specific biochemical signals and physical properties - influence T cell cross-talk with APCs and target cell identification in lymphoid and non-lymphoid organs.

Our laboratory is combining multiple platforms to uncover the molecular and cellular processes that govern tissue-specific adaptive immune responses mediated by cytotoxic CD8⁺ T cells. We follow two main lines of investigation:

• We are examining the role of key regulators governing CD8⁺ T cell activation in lymphoid tissue in preclinical models of immunization and viral infection. From this analysis, we determine the critical decision-making steps at the onset of immune responses and their impact on long-term host protection.

• We investigate the cell biology of tissue-resident memory CD8⁺ T cells at their organ of residence, such as exocrine glands, skin and other non-lymphoid organs. To this end, we examine how these cells integrate local cues for efficient host protection.

Our technical platforms include conventional and spectral flow cytometry, gene expression profiling, microbial infection models, CRISPR/Cas technology, functional ex vivo assays, immunofluorescent tissue analysis, light sheet fluorescence microscopy and twophoton microscopy. The combination of these approaches permits to obtain unprecedented insight into the dynamic nature of the adaptive immune system at the single cell level.