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. 2001 May;14(5):523-34.
doi: 10.1016/s1074-7613(01)00134-0.

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

A Suzuki  1 , M T Yamaguchi, T Ohteki, T Sasaki, T Kaisho, Y Kimura, R Yoshida, A Wakeham, T Higuchi, M Fukumoto, T Tsubata, P S Ohashi, S Koyasu, J M Penninger, T Nakano, T W Mak
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Free article

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

A Suzuki et al. Immunity. 2001 May.
Free article

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 (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 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 Pten(flox/-) mice. PTEN is thus an important regulator of T cell homeostasis and self-tolerance.

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