Understanding the implications of the γδ T cell receptor in the acquisition of IL-17-producing effector functions. 
Ziqing Wang1, Tao Yang1, Inga Sandrock1, Sarina Ravens1
 
1 Institute of Immunology, Hannover Medical School, Hannover, Germany.
 
 
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. Accordingly, murine IL-17 producing γδ T cells are either Vγ6+ or Vγ4+. They 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. To address this question, we took advantage of a mouse model that lacks the Vγ4 and Vγ6 γ-chain (Vγ4-/- / Vγ6-/- double knock-out). Initial results indicate that Vγ1+ T cells produce IL-17 in mice lacking Vγ4+ and Vγ6+ γδTCRs, clearly indicating that the γδTCR does not always instruct the phenotype. Importantly, IL-17+ Vγ1+ T cells were not only present in lymphoid organs, but also at mucosal sites such as the lung and skin. This raises the question about the ontogenetic origin of IL-17+ Vγ1+ T cells and if this instructs their functionality. 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 their Vγ4 and Vγ6 T cell counterparts.