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

Akira Suzuki, Manae Tsukio Yamaguchi, Toshiaki Ohteki, Takehiko Sasaki, Tsuneyasu Kaisho, Yuki Kimura, Tetsuya Higuchi, Manabu Fukumoto, Pamela S. Ohashi, Takeshi Tsubata, Shigeo Koyasu, Toru Nakano, Tak W. Mak

Research output: Contribution to journalArticlepeer-review

489 Citations (Scopus)


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
Issue number5
Publication statusPublished - 2001
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases


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