Immune mediated disease such as inflammatory bowel disease (IBD) is the result of the inappropriate T cell response. There are voids in our understanding of how T cells integrate g-protein mediated chemotactic and chemokinetic """"""""go"""""""" signals with T cell antigen receptor """"""""stop"""""""" signals. Together these signals result in the appropriate T cell response to stimuli. Using the powerful technology of intravital laser scanning confocal microscopy, along with fluorescently labeled T cells and dendritic cells (DC), we aim to define the biophysical dynamics of T-DC interactions in vivo. Next, we aim to define how defects in T cell """"""""stop"""""""" versus """"""""go"""""""" integration, resulting from a null mutation in the g-protein subunit G-alphai2, leads to altered T cell biophysical dynamics and therefore, susceptibility to T cell mediated IBD. Next, we aim to examine how regulatory cells may correct T cell dynamics in G-alphai2 null T cells leading to protection from disease onset and progression. The long-term goal is to therapeutically modulate T cell """"""""stop"""""""" versus """"""""go"""""""" signals to abrogate disease development and progression. ? ? ?
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