Profiling of the early transcriptional response of murine gamma delta T cells following TCR stimulation

gamma delta T cells represent one of the three lineages of lymphocytes, along with alpha beta T cells and B cells, which express antigen receptors. Since their discovery over two decades ago, considerable effort has been made to understand their antigen specificity and their contribution to the immune response. From these studies, we have learned that gamma delta T cells recognize a different set of antigens than alpha beta T cells, acquire effector functions faster than alpha beta T cells, regulate the response of other immune cells during infection, and play distinct roles in immunity. The molecular basis for how gamma delta T cells manifest their unique functions, however, remains unknown. To address this, we profiled the genes upregulated soon after TCR stimulation in order to identify which gene networks associated with T cell effector function are induced in gamma delta T cells. Interestingly, most of the genes in this transcriptional profile were not unique to activated gamma delta T cells, as they were also expressed in activated alpha beta T cells. However, many of the genes within this profile were upregulated with faster kinetics and/or greater magnitude in activated gamma delta T cells than in activated alpha beta T cells. In addition, we found that the genes in the transcriptional profile of activated wild-type gamma delta T cells can be used as a standard to screen activated gamma delta T cells from mice with potential signaling defects for alterations in gamma delta TCR signal transduction. Thus, by defining the early transcriptional response of activated wild-type gamma delta T cells and by comparing their transcriptional profile to that of activated wild-type alpha beta T cells as well as to that of activated gamma delta T cells from signaling defective mice, we are able to gain important insights into the molecular basis for gamma delta T cell function.