The phosphatidylinositol phosphatase PTEN is under control of costimulation and regulates proliferation in human T cells

European Journal of Immunology
Carsten B Schmidt-WeberKurt Blaser

Abstract

The phosphatidylinositol phosphatase gene PTEN is a dual specific phosphatase acting on phospho amino acids but also on three phosphorylated inositol phospholipids. Present results demonstrate that PTEN is inducible by costimulatory signals in human CD4(+) T cells. PTEN expression was up-regulated on RNA and protein level in freshly isolated human CD4(+) T cells following stimulation with CD28 or CD2. In contrast, PTEN expression was high but remained CD28 and CD2 unresponsive in lymphoma cells. Intracellular staining revealed PTEN expression in CD4(+) T cell populations stimulated with anti-CD28 or anti-CD28 / anti-CD3. Stimulation with anti-CD3 alone did not induce PTEN expression. Inhibition of PTEN expression by antisense oligonucleotides in CD4(+) T cells stimulated with non-mitogenic anti-CD28 resulted in massively increased proliferation, which was sensitive to the phosphatidylinositol 3-kinase (PI3 K) inhibitor wortmannin. Although CD28 and CD2 induce PI3 K signal transduction, wortmannin did not block PTEN up-regulation by CD28 or CD2 indicating that PTEN gene expression is PI3 K independent. These results demonstrate that PTEN negatively controls costimulatory signals by antagonizing PI3 K activity in the absence of T...Continue Reading

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Citations

Oct 6, 2007·Immunologic Research·Masaki KashiwadaPaul B Rothman
Jun 22, 2005·International Immunology·Carsten B Schmidt-WeberKurt Blaser
Nov 3, 2005·Current Opinion in Allergy and Clinical Immunology·Carsten B Schmidt-Weber, Kurt Blaser
Jul 16, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Frederick L LockeThomas F Gajewski
Apr 3, 2003·Immunological Reviews·Maria-Cristina Seminario, Ronald L Wange
Oct 1, 2005·Leukemia & Lymphoma·Ayşegül H UnerSevket Ruacan

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