The Journal of Experimental Medicine
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Published 19 November 2001. doi:10.1084/jem.194.10.1473
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© Rockefeller University Press, 0022-1007/2001/11/1473/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 10, November 19, 2001 1473-1483

Original Article

 T Cell Receptor Specificity Is Critical for the Development of Epidermal {gamma}{delta} T Cells

Isabel Ferrero1, Anne Wilson1, Friedrich Beermann2, Werner Held1 and H. Robson MacDonald1

1 Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne
2 Swiss Institute for Experimental Cancer Research, CH-1066 Epalinges, Switzerland

Address correspondence to H. Robson MacDonald, Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, CH-1066 Epalinges, Switzerland. Phone: 41-21-692-5989; Fax: 41-21-653-4474; E-mail: hughrobson.macdonald{at}isrec.unil.ch

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{gamma}3/V{delta}1. These cells, referred to as dendritic epidermal T cells (DETC) originate from fetal V{gamma}3+ 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{delta}6.3-D{delta}1-D{delta}2-J{delta}1-C{delta}), which can pair with V{gamma}3 in fetal thymocytes but is not normally expressed by DETC. In wild-type (wt) V{delta}6.3Tg mice DETC were present and virtually all of them express V{delta}6.3. However, DETC were absent in TCR-{delta}-/- V{delta}6.3Tg mice, despite the fact that V{delta}6.3Tg {gamma}{delta} T cells were present in normal numbers in other lymphoid and nonlymphoid tissues. In wt V{delta}6.3Tg mice, a high proportion of in-frame V{delta}1 transcripts were found in DETC, suggesting that the expression of an endogenous TCR-{delta} (most probably V{delta}1) was required for the development of V{delta}6.3+ 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.

Key Words: {gamma}{delta} T cells • repertoire selection • migration • epidermis • allelic exclusion


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