Development of dendritic epidermal T cells with a skewed diversity of γδTCRs in Vδ1-deficient mice

One of the most intriguing features of gamma delta T cells that reside in murine epithelia is the association of a specific V gamma/V delta usage with each epithelial tissue. Dendritic epidermal T cells (DETCs) in the murine epidermis, are predominantly derived from the "first wave" V gamma 5(+) fetal thymocytes and overwhelmingly express the canonical V gamma 5/V delta 1-TCRs lacking junctional diversity, Targeted disruption of the V delta 1 gene resulted in a markedly impaired development of V gamma 5(+) fetal thymocytes as precursors of DETCs; however, gamma delta TCR+ DETCs with a typical dendritic morphology were observed in V delta 1(-/-) mice and their cell densities in the epidermis were slightly lower than those in V delta 1(+/-) epidermis, Moreover, the V delta 1-deficient DETCs were functionally competent in their ability to up-regulate cytokines and keratinocyte growth factor-expression in response to keratinocytes, V gamma 5(+) DETCs were predominant in the V delta 1(-/-) epidermis, though V gamma 5(-) gamma delta TCR+ DETCs were also detected, The V gamma 5(+) DETCs showed a typical dendritic shape, gamma delta TCRhigh, and age-associated expansion in epidermis as observed in conventional DETCs of normal mid, whereas the V gamma 5(-) gamma delta TCR+ DETCs showed a less dendritic shape, gamma delta TCRlow, and no expansion in the epidermis, consistent with their immaturity. These results suggest that optimal DETC development does not require a particular V gamma/V delta-chain usage but requires expression of a limited diversity of gamma delta TCRs, which allow DETC precursors to mature and expand within the epidermal microenvironment.