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

Abstract

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