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Phosphoinositide‐dependent kinase l (PDK1) haplo‐insufficiency inhibits production of alpha/beta (α/β) but not gamma delta (γ/δ) T lymphocytes
Author(s) -
Kelly April P.,
Hinton Heather J.,
Clarke Rosemary G.,
Cantrell Doreen A.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.03.022
Subject(s) - t cell , microbiology and biotechnology , cell cycle , biology , progenitor cell , thymocyte , apoptosis , stem cell , immunology , immune system , genetics
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.