title: Pten loss in CD4 T cells enhances their helper function but does not lead to autoimmunity or lymphoma.
abstract: PTEN, one of the most commonly mutated or lost tumor suppressors in human cancers, antagonizes signaling by the PI3K pathway. Mice with thymocyte-specific deletion of Pten rapidly develop peripheral lymphomas and autoimmunity, which may be caused by failed negative selection of thymocytes or from dysregulation of postthymic T cells. We induced conditional deletion of Pten from CD4 Th cells using a Cre knocked into the Tnfrsf4 (OX40) locus to generate OX40(Cre)Pten(f) mice. Pten-deficient Th cells proliferated more and produced greater concentrations of cytokines. The OX40(Cre)Pten(f) mice had a general increase in the number of lymphocytes in the lymph nodes, but not in the spleen. When transferred into wild-type (WT) mice, Pten-deficient Th cells enhanced anti-Listeria responses and the clearance of tumors under conditions in which WT T cells had no effect. Moreover, inflammatory responses were exaggerated and resolved later in OX40(Cre)Pten(f) mice than in WT mice. However, in contrast with models of thymocyte-specific Pten deletion, lymphomas and autoimmunity were not observed, even in older OX40(Cre)Pten(f) mice. Hence loss of Pten enhances Th cell function without obvious deleterious effects.
authors.affiliation: Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, United Kingdom.
authors.forename: Dalya R
authors.initials: DR
authors.lastname: Soond
authors.forename: Fabien
authors.initials: F
authors.lastname: Garçon
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Patton
authors.forename: Julia
authors.initials: J
authors.lastname: Rolf
authors.forename: Martin
authors.initials: M
authors.lastname: Turner
authors.forename: Cheryl
authors.initials: C
authors.lastname: Scudamore
authors.forename: Oliver A
authors.initials: OA
authors.lastname: Garden
authors.forename: Klaus
authors.initials: K
authors.lastname: Okkenhaug
mesh_terms: D000818:Animals; D015551:Autoimmunity; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005434:Flow Cytometry; D055879:Gene Knock-In Techniques; D006706:Homeostasis / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008223:Lymphoma / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D051059:PTEN Phosphohydrolase / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology
chemical_list: D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse