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

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