Transcriptional programming and gene regulation in WC1+ γδ T cell subpopulations

Abstract

γδ T cells represent a high proportion of lymphocytes in the blood of ruminants with the majority expressing lineage-specific glycoproteins from the WC1 family. WC1 receptors are coded for by a multigenic array whose genes have variegated but stable expression among cells in the γδ T cell population. WC1 molecules function as hybrid pattern recognition receptors as well as co-receptors for the TCR and are required for responses by the cells. Because of the variegated gene expression, WC1⁺ γδ T cells can be divided into two main populations known as WC1.1⁺ and WC1.2⁺ based on monoclonal antibody reactivity with the expressed WC1 molecules. These subpopulations differ in their ability to respond to specific pathogens. Here, we showed these populations are established in the thymus and that WC1.1⁺ and WC1.2⁺ subpopulations have transcriptional programming that is consistent with stratification towards Tγδ1 or Tγδ17. WC1.1⁺ cells exhibited the Tγδ1 phenotype with greater transcription of Tbx21 and production of more IFNγ while the WC1.2⁺ subpopulation tended towards Tγδ17 programming producing higher levels of IL-17 and had greater transcription of Rorc. However, when activated both WC1⁺ subpopulations' cells transcribed Tbx21 and secreted IFNγ and IL-17 reflecting the complexity of these subpopulations defined by WC1 gene expression. The gene networks involved in development of these two subpopulations including expression of their archetypal genes wc1-3 (WC1.1⁺) and wc1-4 (WC1.2⁺) were unknown but we report that SOX-13, a γδ T cell fate-determining transcription factor, has differential occupancy on these WC1 gene loci and suggest a model for development of these subpopulations.

Keywords: IFNγ; IL-17; SOX-13; Thymic signaling; Tγδ1; Tγδ17; WC1; γδ T cells.