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

γδ T cells represent one of the three lineages of lymphocytes, along with αβ 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 γδ T cells recognize a different set of antigens than αβ T cells, acquire effector functions faster than αβ T cells, regulate the response of other immune cells during infection, and play distinct roles in immunity. The molecular basis for how γδ 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 γδ T cells. Interestingly, most of the genes in this transcriptional profile were not unique to activated γδ T cells, as they were also expressed in activated αβ T cells. However, many of the genes within this profile were upregulated with faster kinetics and/or greater magnitude in activated γδ T cells than in activated αβ T cells. In addition, we found that the genes in the transcriptional profile of activated wild-type γδ T cells can be used as a standard to screen activated γδ T cells from mice with potential signaling defects for alterations in γδTCR signal transduction. Thus, by defining the early transcriptional response of activated wild-type γδ T cells and by comparing their transcriptional profile to that of activated wild-type αβ T cells as well as to that of activated γδ T cells from signaling defective mice, we are able to gain important insights into the molecular basis for γδ T cell function.