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Development of TCR gamma delta iIELs
1Department of Medicine, Lakeside Veteran's Administration Hospital, Chicago, USA.
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 TCR gamma delta iIEL development has been to utilize G8 transgenic (Tg) mice expressing an antigen-specific, developmentally-regulated, gamma delta TCR. These mice have provided a useful tool to dissect T-cell development of intestinal TCR gamma delta cells. In this review, we summarize our findings of studies using this model system to dissect the complex events that regulate TCR gamma delta iIEL development and functional activity. The data suggest a maturational scheme for TCR gamma delta iIELs wherein the majority of TCR gamma delta iIELs migrate to the gut in an immature state where they develop in response to TCR ligation. As TCR gamma delta iIELs develop, surface and functional phenotypes change in a discernable pattern. These findings provide an important first step in analysing TCR gamma delta development, maturation and differentiation in normal animals.
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 TCR gamma delta iIEL development has been to utilize G8 transgenic (Tg) mice expressing an antigen-specific, developmentally-regulated, gamma delta TCR. These mice have provided a useful tool to dissect T-cell development of intestinal TCR gamma delta cells. In this review, we summarize our findings of studies using this model system to dissect the complex events that regulate TCR gamma delta iIEL development and functional activity. The data suggest a maturational scheme for TCR gamma delta iIELs wherein the majority of TCR gamma delta iIELs migrate to the gut in an immature state where they develop in response to TCR ligation. As TCR gamma delta iIELs develop, surface and functional phenotypes change in a discernable pattern. These findings provide an important first step in analysing TCR gamma delta development, maturation and differentiation in normal animals.