TY - JOUR
T1 - T cell-specific loss of Pten leads to defects in central and peripheral tolerance
AU - Suzuki, Akira
AU - Yamaguchi, Manae Tsukio
AU - Ohteki, Toshiaki
AU - Sasaki, Takehiko
AU - Kaisho, Tsuneyasu
AU - Kimura, Yuki
AU - Higuchi, Tetsuya
AU - Fukumoto, Manabu
AU - Ohashi, Pamela S.
AU - Tsubata, Takeshi
AU - Koyasu, Shigeo
AU - Nakano, Toru
AU - Mak, Tak W.
N1 - Funding Information:
We would like to thank Tetsuo Noda (Tohoku University), Shin Yonehara (Kyoto University), Toshifumi Matsuyama (Nagasaki University), Hiroaki Takimoto (Kitazato University), Harumi Suzuki, Satoshi Matsuda (Keio University), Vuk Stambolic, Annick Itie, Wilson Khoo (Amgen Institute), and Nana Iwami (Osaka University) for technical assistance and helpful discussions; Mary Saunders for scientific editing; and Miki Sato Suzuki for her valuable assistance. This work was partially supported by grants from the Ministry of Education, Science, Sports, and Culture, Japan, and from the Future Program of Japanese Society for Promotion of Sciences (JSPS-RFTF98L01101), the National Cancer Institute of Canada (NCIC), and the Canadian Breast Cancer Research Institute (CBCRI).
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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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U2 - 10.1016/S1074-7613(01)00134-0
DO - 10.1016/S1074-7613(01)00134-0
M3 - Article
C2 - 11371355
AN - SCOPUS:0034995242
SN - 1074-7613
VL - 14
SP - 523
EP - 534
JO - Immunity
JF - Immunity
IS - 5
ER -
