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

A. Suzuki, 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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439 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)523-534
Number of pages12
JournalImmunity
Volume14
Issue number5
DOIs
Publication statusPublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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    Suzuki, A., Yamaguchi, M. T., Ohteki, T., Sasaki, T., Kaisho, T., Kimura, Y., Yoshida, R., Wakeham, A., Higuchi, T., Fukumoto, M., Tsubata, T., Ohashi, P. S., Koyasu, S., Penninger, J. M., Nakano, T., & Mak, T. W. (2001). T cell-specific loss of Pten leads to defects in central and peripheral tolerance. Immunity, 14(5), 523-534. https://doi.org/10.1016/S1074-7613(01)00134-0