| First Author | Soond DR | Year | 2012 |
| Journal | J Immunol | Volume | 188 |
| Issue | 12 | Pages | 5935-43 |
| PubMed ID | 22611241 | Mgi Jnum | J:188961 |
| Mgi Id | MGI:5442669 | Doi | 10.4049/jimmunol.1102116 |
| Citation | Soond DR, et al. (2012) Pten loss in CD4 T cells enhances their helper function but does not lead to autoimmunity or lymphoma. J Immunol 188(12):5935-43 |
| abstractText | 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. |
