Transcriptomes of clonally explanded human effector Gamma9Delta2 T cells

In this study dedicated to the transcriptional, phenotypic and functional diversity of the human Gamma9Delta2 T cells we probed an array of in vitro-generated clones maintained using rapid expansion protocol (REP) which involves repetitive exposure to feeder cells, IL-2 and IL-15. Based on functional readouts in co-cultures with tumor cells we identified gradients of type 1 and, unexpectedly, type 2-like functionalities among the clones maintained in these type 1-polarizing conditions. Functional readouts were supported by in-depth transcriptional profiling. A gradient of activation, supposedly partially driven by VGamma9VDelta2TCR signaling, appears to shape this transcriptional and functional heterogeneity. Stronger activation drives a type 1-oriented state, marked by a signature IFNgamma response, enhanced proliferation, and polyfunctionality - traits that are particularly valuable for immunotherapy applications.