Phosphoinositide-dependent kinase l (PDK1) haplo-insufficiency inhibits production of alpha/beta (α/β) but not gamma delta (γ/δ) T lymphocytes

In the present study, we have explored the impact of deleting a single allele of PDK1 in T cell progenitors on α/β and γ/δ T cell development. The data show that deleting a single allele of PDK1 allows differentiation of α/β T cells but prevents their proliferative expansion in the thymus. Accordingly, mice with T cells that are haplo-insufficient for PDK1 have reduced numbers of thymocytes and α/β peripheral T cells. T cell progenitors also give rise to γ/δ T cells but in contrast to the loss of α/β T cells in T-PDK1 null and haplo-insufficient mice, there were increased numbers of γ/δ T cells. The production of α/β T cells is dependent on the proliferative expansion of thymocytes and is determined by a balance between the frequency with which cells enter the proliferative phase of the cell cycle and rates of cell death. Herein, we show that PDK1 haplo-insufficient thymocytes have no defects in their ability to enter the cell cycle but show increased apoptosis. PDK1 thus plays a determining role in the development of α/β T lymphocytes but does not limit γ/δ T cell development.