T cell receptor specificity is critical for the development of epidermal γδ T cells

A particular feature of gamma delta T cell biology is that cells expressing T cell receptor (TCR) using specific V gamma /V delta segments are localized in distinct epithelial sites, e.g., in mouse epidermis nearly all gamma delta T cells express V gamma3/V delta1. These cells, referred to as dendritic epidermal T cells (DETC) originate from fetal V gamma3(+) thymocytes. The role of gamma delta TCR specificity in DETC's migration/localization to the skin has remained controversial. To address this issue we have generated transgenic (Tg) mice expressing a TCR delta chain (V delta6.3-D delta1-D delta2-J delta1-C delta), which can pair with V gamma3 in fetal thymocytes but is not normally expressed by DETC. In wild-type (wt) V delta6.3Tg mice DETC were present and virtually all of them express V delta6.3. However, DETC were absent in TCR-delta (-/-) V delta6.3Tg mice, despite the fact that V delta6.3Tg gamma delta T cells were present in normal numbers in other lymphoid and nonlymphoid tissues. In wt V delta6.3Tg mice, a high proportion of in-frame V delta1 transcripts were found in DETC, suggesting that the expression of an endogenous TCR-delta (most probably V delta1) was required for the development of V delta6.3+ epidermal gamma delta T cells. Collectively our data demonstrate that TCR specificity is essential for the development of gamma delta T cells in the epidermis. Moreover, they show that the TCR-delta locus is not allelically excluded.