Common and Exclusive Features of Intestinal Intraepithelial γδ T Cells and Other γδ T Cell Subsets

Murine peripheral lymph node TCR γδ T cells have been divided into type 1 and type 17 functional categories based on phenotypic and functional markers. Localized in the gut epithelial barrier, intestinal intraepithelial lymphocytes (iIEL) γδ T cells constitute a peculiar subset of T lymphocytes involved in intestinal homeostasis. However, whether iIEL γδ T cells obey the type 1/type 17 dichotomy is unclear. Using both global transcriptional signatures and expression of cell surface markers, we reveal that murine iIEL γδ T cells compose a distinct population, expressing ∼1000 specific genes, in particular genes that are responsible for cytotoxicity and regulatory functions. The expression of the transcription factor Helios is a feature of iIEL γδ T cells, distinguishing them from the other TCR γδ T subsets, including those present in the epithelia of other tissues. The marked expression of Helios is also shared by the other iIELs, TCRαβCD8αα lymphocytes present within the intestinal epithelium. Finally, we show that Helios expression depends in part on TGF-β signaling but not on the microbiota. Thus, our study proposes iIEL γδ T cells as a distinct subset and identifies novel markers to differentiate them from their peripheral counterparts.