부산대학교 도서관

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.febslet.2006.03.022 Byline: April P. Kelly (a), Heather J. Hinton (b), Rosemary G. Clarke (a), Doreen A. Cantrell (a) Keywords: PDK1; Gamma delta T lymphocytes; Haplo-insufficiency Abbreviations: DAPI; 4',6-diamidino-2-phenylindole; DN, double negative; DP, double positive; FSC, forward scatter; MHC, major histocompatibility complex; NLC, normal littermate control; PDK-1, 3'-phosphoinositide-dependent protein kinase 1; PI, propidium iodine; SP, single positive Abstract: In the present study, we have explored the impact of deleting a single allele of PDK1 in T cell progenitors on [alpha]/[beta] and [gamma]/[delta] T cell development. The data show that deleting a single allele of PDK1 allows differentiation of [alpha]/[beta] 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 [alpha]/[beta] peripheral T cells. T cell progenitors also give rise to [gamma]/[delta] T cells but in contrast to the loss of [alpha]/[beta] T cells in T-PDK1 null and haplo-insufficient mice, there were increased numbers of [gamma]/[delta] T cells. The production of [alpha]/[beta] 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 [alpha]/[beta] T lymphocytes but does not limit [gamma]/[delta] T cell development. Author Affiliation: (a) Division of Cell Biology and Immunology, School of Life Sciences, WTB Complex, University of Dundee, Dow Street, Dundee DD1 5EH, UK (b) Cytos Biotechnology AG, Wagistrasse 25, 8952 Zurich-Schlieren, Switzerland Article History: Received 3 January 2006; Revised 20 February 2006; Accepted 7 March 2006