THE DEVELOPMENTAL FATE OF T-CELLS IS CRITICALLY INFLUENCED BY TCR-GAMMA-DELTA EXPRESSION

Differentiation of gamma delta and alpha beta T cells from a common pr ecursor 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 tra nsgene competitively inhibits alpha beta thymocyte development under c onditions where TCR beta gene rearrangement is limiting. The status of TCR delta gene rearrangements in the remaining alpha beta-lineage cel ls indicates that the effect is mediated by the intact gamma delta rec eptor. Paradoxically, in TCR beta(-/-) mice, gamma delta receptor expr ession can also drive differentiation of some up-lineage cells. To res olve 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-pr one or stochastic.