Blockage of αβ T-cell development by TCR γδ transgenes

Abstract

T LYMPHOCYTES recognize antigens by means of T-cell receptors (TCR) composed of αβ (refs 1–3) or γδ heterodimers^4–6. The mechanism governing the development of αβ- and γδ-bearing T cells from a common precursor T cell is so far unknown. It has been proposed that T-cell precursors rearrange their γ- and δ-chain genes first, and αβ T cells are generated only from those cells that fail to rearrange productively both γ- and δ-chain genes^7,8. Our recent study on γδ-transgenic mice contradicted this hypothesis, however, and indicated that repression of γ-chain gene expression mediated by a transcriptional silencer element has a critical role in the generation of αβ T cells⁹. Here we report that the generation of a αβ T cells is severely blocked in transgenic mice carrying γ- and δ-chain transgenes without the associated silencer, thereby strengthening the validity of the silencer model of T-cell development.