Investigating in the implications of the γδ T cell receptor in the acquisition of IL-17 producing effector functions

One common way to classify functional γδ T cell subsets is based on the expressed variable gene region of the T-cell-receptor (TCR) γ-chain. It is established that the TCRs of murine IL-17 producing γδ T cells are either Vγ6+ or Vγ4+. The majority of IL-17 producers get functionally pre-programmed in the prenatal thymus, and persist thereafter as tissue-resident cells into adulthood. Little is known about the role of the expressed TCR on IL-17 effector fate acquisition, and if also other subsets can produce IL-17 under certain circumstances. To address this question, we took advantage of a mouse model that lack the Vγ4 and Vγ6 γ-chain (Vγ4-/- / Vγ6-/- double knock-out). Initial results indicate that Vγ1+ T cells show increased IL-17 production capability in the absence of Vγ4+ and Vγ6+ γδ T cells, suggesting that the γδTCR does not always instruct the phenotype. This raises the question about the ontogenetic origin, which might be a TCR-independent default mechanism to instruct IL-17 production by γδ T cells, of IL-17+ Vγ1+ T cells. Moreover, it remains elusive if these Vγ1+ T cells (i) adopt highly similar tissue-specific gene expression programs and (ii) functionality in health and disease, than the Vγ4+ and Vγ6+ T cells. To elucidate whether IL-17pos and IL-17neg Vγ1+ T cells show a similar or a different TCR repertoire diversity, an mRNA-based next-generation sequencing analysis of δ-chain sequences (TCR-seq) was performed on FACS-sorted IL-17pos and IL-17neg γδ T cells from pLNs of Vγ4-/- / Vγ6-/- mice.