| First Author | Johnson TA | Year | 2008 |
| Journal | Am J Pathol | Volume | 172 |
| Issue | 4 | Pages | 980-92 |
| PubMed ID | 18349128 | Mgi Jnum | J:133344 |
| Mgi Id | MGI:3778313 | Doi | 10.2353/ajpath.2008.070892 |
| Citation | Johnson TA, et al. (2008) Antigen-induced pten gene deletion in T cells exacerbates neuropathology in experimental autoimmune encephalomyelitis. Am J Pathol 172(4):980-92 |
| abstractText | The Pten tumor suppressor gene is critical for normal intrathymic development of T cells; however, its role in mature antigen-activated T cells is less well defined. A genetically crossed mouse line, Pten(fl/fl) GBC, in which Pten gene deletions could be primarily confined to antigen-activated CD8(+) T cells, enabled us to evaluate the consequences of Pten loss on the course of experimental autoimmune encephalomyelitis. Compared with Pten(fl/fl) controls, myelin oligodendrocyte glycoprotein (MOG) peptide-immunized Pten(fl/fl) GBC mice developed more severe and protracted disease. This was accompanied by increased spinal cord white matter myelin basic protein depletion and axonal damage, as well as a striking persistence of macrophage and granzyme B-expressing cellular neuroinfiltrates in the chronic phase of the disease. This persistence may be explained by the observation that anti-CD3 activated Pten(fl/fl) GBC T cells were more resistant to proapoptotic stimuli. Consistent with the predicted consequences of Pten loss, purified CD8(+) T cells from Pten(fl/fl) GBC mice displayed augmented proliferative responses to anti-T-cell receptor stimulation, and MOG-primed Pten(fl/fl) GBC T cells exhibited a reduced activation threshold to MOG peptide. Pten(fl/fl) GBC mice also developed atypical central nervous system disease, manifested by prominent cervical cord and forebrain involvement. Collectively, our findings indicate that the phosphatidylinositol 3-kinase signaling pathway is an essential regulator of CD8(+) T-cell effector function in experimental autoimmune encephalomyelitis. |
