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Research at OU

Biology

  T Cell-Specific Loss of Pten Leads to Defects in Central and Peripheral Tolerance

 

 

PTEN, a tumor suppressor gene, is essential for embryogenesis. We used the Cre-loxP system to generate a T cell-specific deletion of the Pten gene (PTEN mice). All PTEN mice develop T cell lymphomas by 17 weeks. PTEN mice show increased thymic cellularity due in part to a defect in thymic negative selection. Impaired negative thymic selection caused autoimmune small cell infiltration into perivascular areas and some alveolar septa of the lungs (arrows, B: bronchus, V: blood vessels). PTEN mice exhibit elevated levels of B cells and CD4+ T cells in the periphery, spontaneous activation of CD4+ T cells, autoantibody production, and hyper-gammaglobulinemia. PTEN T cells hyperproliferate, are autoreactive, secrete increased levels of Th1/Th2 cytokines, resist apoptosis, and show increased phosphorylation of PKB/Akt and ERK. PTEN is thus an important regulator of T cell home

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