The Loss of PTEN Allows TCR alpha beta Lineage Thymocytes to Bypass IL-7 and Pre-TCR-mediated Signaling

The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) negatively regulates cell survival and proliferation mediated by phosphoinositol 3 kinases. We have explored the role of the phosphoinositol(3,4,5)P3-phosphatase PTEN in T cell development by analyzing mice with a T cell-specific d...

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Published in:The Journal of experimental medicine 2004-10, Vol.200 (7), p.883-894
Main Authors: Hagenbeek, Thijs J, Naspetti, Marianne, Malergue, Fabrice, Garcon, Fabien, Nunes, Jacques A, Cleutjens, Kitty BJM, Trapman, Jan, Krimpenfort, Paul, Spits, Hergen
Format: Article
Language:English
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Summary:The phosphatase and tensin homologue deleted on chromosome 10 (PTEN) negatively regulates cell survival and proliferation mediated by phosphoinositol 3 kinases. We have explored the role of the phosphoinositol(3,4,5)P3-phosphatase PTEN in T cell development by analyzing mice with a T cell-specific deletion of PTEN. Pten super(flox/flox)Lck-Cre mice developed thymic lymphomas, but before the onset of tumors, they showed normal thymic cellularity. To reveal a regulatory role of PTEN in proliferation of developing T cells we have crossed PTEN- deficient mice with mice deficient for interleukin (IL)-7 receptor and pre-T cell receptor (TCR) signaling. Analysis of mice deficient for Pten and CD3 gamma ; Pten and gamma c; or Pten, gamma c, and Rag2 revealed that deletion of PTEN can substitute for both IL-7 and pre-TCR signals. These double- and triple-deficient mice all develop normal levels of CD4CD8 double negative and double positive thymocytes. These data indicate that PTEN is an important regulator of proliferation of developing T cells in the thymus.
ISSN:0022-1007
1892-1007
DOI:10.1084/jem.20040495