The Developmental Fate of T Cells Is Critically Influenced by TCRγδ Expression

Abstract

Differentiation of γδ and αβ T cells from a common precursor cell depends on productive rearrangement and expression of TCRγδ or TCRβ genes, but whether it is an instructive or a stochastic mechanism that is responsible for this process is unclear. We report that expression of the productively rearranged TCRγ transgene competitively inhibits αβ thymocyte development under conditions where TCRβ gene rearrangement is limiting. The status of TCRδ gene rearrangements in the remaining αβ-lineage cells indicates that the effect is mediated by the intact γδ receptor. Paradoxically, in TCRβ−/− mice, γδ receptor expression can also drive differentiation of some αβ-lineage cells. To resolve this paradox, we provide evidence for a minor population of γδ-dependent αβ-lineage cells in normal mice. The results indicate that the T cell lineage commitment process is either error-prone or stochastic.