Nurturing the phenotype: Environmental signals and transcriptional regulation of intestinal γδ T cells.

The intestinal epithelium harbours a unique lymphocyte population, the intraepithelial lymphocytes (IELs). A large fraction of IELs is represented by γδ T cells. Their role in epithelial homeostasis and immune response is well documented, but a conclusive view of their developmental pathway is still missing. In this review, we discuss the existing literature as well as recent advances regarding the tissue adaptation of γδ IELs, both for the characteristic cytotoxic subset and the newly described noncytotoxic subset. We particularly highlight the environmental cues and the transcriptional regulation that equip γδ T cells with their IEL phenotype.

A monoclonal Trd chain supports the development of the complete set of functional γδ T cell lineages.

The clonal selection theory describes key features of adaptive immune responses of B and T cells. For αß T cells and B cells, antigen recognition and selection principles are known at a detailed molecular level. The precise role of the antigen receptor in γδ T cells remains less well understood. To better understand the role of the γδ T cell receptor (TCR), we generate an orthotopic TCRδ transgenic mouse model. We demonstrate a multi-layered functionality of γδ TCRs and diverse roles of CDR3δ-mediated selection during γδ T cell development. Whereas epithelial populations using Vγ5 or Vγ7 chains are almost unaffected in their biology in the presence of the transgenic TCRδ chain, pairing with Vγ1 positively selects γδ T cell subpopulations with distinct programs in several organs, thereby distorting the repertoire. In conclusion, our data support dictation of developmental tropism together with adaptive-like recognition principles in a single antigen receptor.