The developmental fate of T cells is critically influenced by TCRγδ expression

Differentiation of gamma delta and alpha beta T cells from a common precursor cell depends on productive rearrangement and expression of TCR gamma delta or TCR beta 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 TCR gamma transgene competitively inhibits alpha beta thymocyte development under conditions where TCR beta gene rearrangement is limiting. The status of TCR delta gene rearrangements in the remaining alpha beta-lineage cells indicates that the effect is mediated by the intact gamma delta receptor. Paradoxically, in TCR beta(-/-) mice, gamma delta receptor expression can also drive differentiation of some up-lineage cells. To resolve this paradox, we provide evidence for a minor population of gamma delta-dependent alpha beta-lineage cells in normal mice. The results indicate that the T cell lineage commitment process is either error-prone or stochastic.