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.
Highlights
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
PI3K signaling in OX40CrePtenf T cells is sustained In OX40Cre mice, Cre is expressed almost exclusively in activated CD4 T cells and regulatory T cell (Treg), and only 2–5% of CD8 T cells [35]
We have shown in this article that Pten is not an essential tumor suppressor in peripheral CD4 Th cells
Summary
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. PI3K signaling in OX40CrePtenf T cells is sustained In OX40Cre mice, Cre is expressed almost exclusively in activated CD4 T cells and Tregs, and only 2–5% of CD8 T cells [35].
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
