Development of TCRγδ iIELs

Interest has focused recently on the development and function of T and B lymphocytes in the mucosal surface, particularly on a population of intestinal intraepithelial lymphocytes (iIELs) that develop by thymic and extrathymic pathways in the mucosa (for review see ref 1). Our approach to studying TCRγδ iIEL development has been to utilize G8 transgenic (Tg) mice expressing an antigen-specific, developmentally-regulated, γδTCR. These mice have provided a useful tool to dissect T-cell development of intestinal TCRγδ cells. In this review, we summarize our findings of studies using this model system to dissect the complex events that regulate TCRγδ iIEL development and functional activity. The data suggest a maturational scheme for TCRγδ iIELs wherein the majority of TCRγδ iIELs migrate to the gut in an immature state where they develop in response to TCR ligation. As TCRγδ iIELs develop, surface and functional phenotypes change in a discernable pattern. These findings provide an important first step in analysing TCRγδ development, maturation and differentiation in normal animals.