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PMID: 11371355 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

Immunity ·Vol. 14 ·No. 5 ·2001-05-00 ·Pages 523-34

Suzuki A, Yamaguchi MT, Ohteki T, Sasaki T, Kaisho T, Kimura Y, Yoshida R, Wakeham A, Higuchi T, Fukumoto M, Tsubata T, Ohashi PS, Koyasu S, Penninger JM, Nakano T, Mak TW

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.

MeSH Terms

Animals Apoptosis/immunology CD4-Positive T-Lymphocytes/cytology,immunology Cell Division Cytokines/biosynthesis DNA-Binding Proteins/metabolism Enterotoxins/immunology Female Genes, Tumor Suppressor I-kappa B Proteins Immune Tolerance Lymphatic Diseases/immunology Lymphoma, T-Cell/immunology Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Mitogen-Activated Protein Kinases/metabolism PTEN Phosphohydrolase Phosphoric Monoester Hydrolases/genetics,immunology Protein Serine-Threonine Kinases Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-akt Proto-Oncogene Proteins c-bcl-2/metabolism Receptors, Antigen/genetics,immunology Receptors, Antigen, T-Cell/genetics,immunology Splenomegaly Staphylococcus aureus/immunology Superantigens/immunology Thymus Gland/abnormalities,cytology Tumor Suppressor Proteins

Chemicals

Cytokines DNA-Binding Proteins Enterotoxins H-Y antigen receptor I kappa B beta protein I-kappa B Proteins Proto-Oncogene Proteins Proto-Oncogene Proteins c-bcl-2 Receptors, Antigen Receptors, Antigen, T-Cell Superantigens Tumor Suppressor Proteins enterotoxin B, staphylococcal Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Mitogen-Activated Protein Kinases Phosphoric Monoester Hydrolases PTEN Phosphohydrolase

Authors & Affiliations

16 authors, click to expand affiliations / ORCID

Suzuki A

Department of Molecular and Cellular Biology, Osaka University, 565-0871, Osaka, Japan.

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

Article Info

Journal

Immunity

Abbr.

Immunity

ISSN

1074-7613

DOI

10.1016/s1074-7613(01)00134-0

Published

2001-05-00

Pages

523-34

Language

English

Region

United States

NLM ID

9432918

Subset

External Links

PubMed source DOI: 10.1016/s1074-7613(01)00134-0 View journal details

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

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