[PDF][PDF] T cell-specific loss of Pten leads to defects in central and peripheral tolerance

A Suzuki, MT Yamaguchi, T Ohteki, T Sasaki, T Kaisho… - Immunity, 2001 - cell.com
A Suzuki, MT Yamaguchi, T Ohteki, T Sasaki, T Kaisho, Y Kimura, R Yoshida, A Wakeham…
Immunity, 2001cell.com
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 flox/− mice). All Pten
flox/− mice develop CD4+ T cell lymphomas by 17 weeks. Pten flox/− mice show increased
thymic cellularity due in part to a defect in thymic negative selection. Pten flox/− mice exhibit
elevated levels of B cells and CD4+ T cells in the periphery, spontaneous activation of CD4+
T cells, autoantibody production, and hypergammaglobulinemia. Pten flox/− T cells …
Abstract
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 (Ptenflox/− mice). All Ptenflox/− mice develop CD4+ T cell lymphomas by 17 weeks. Ptenflox/− mice show increased thymic cellularity due in part to a defect in thymic negative selection. Ptenflox/− mice exhibit elevated levels of B cells and CD4+ T cells in the periphery, spontaneous activation of CD4+ T cells, autoantibody production, and hypergammaglobulinemia. Ptenflox/− T cells hyperproliferate, are autoreactive, secrete increased levels of Th1/Th2 cytokines, resist apoptosis, and show increased phosphorylation of PKB/Akt and ERK. Peripheral tolerance to SEB is also impaired in Ptenflox/− mice. PTEN is thus an important regulator of T cell homeostasis and self-tolerance.
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