Our group is interested in understanding how signaling from antigen receptors, costimulatory molecules and cytokines determines lymphocyte fate. Our working hypothesis is that lymphocyte differentiation is a progressive process determined by the cumulative strength of stimulation (i.e. intensity and duration) resulting from the stochastic exposure of T cells to antigen presenting cells and cytokines. Progression through hierarchical thresholds for proliferation and differentiation result in the generation of various intermediates and terminally differentiated effector cells, which are then selected according to their survival and homing capacity. We are also investigating the mechanisms that maintain immunological memory. Our working hypothesis is that intermediates of the lymphocyte differentiation process persist in secondary lymphoid organs as central memory T or memory B lymphocytes that can proliferate and differentiate to effector T cells and plasma cells not only in response to antigen but also to polyclonal stimuli (such as cytokines or bystander help). This “stem cell” property of memory lymphocytes provides a means to maintain, in the absence of antigen, a constant level of effector T cells and antibodies that confers immediate protection for a lifetime. These studies are performed in the human system and have relevance to vaccination and immunotherapy.
See our home, the Institute for Research in Biomedicine in Bellinzona.
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