| First Author | Buckler JL | Year | 2006 |
| Journal | J Immunol | Volume | 177 |
| Issue | 7 | Pages | 4262-6 |
| PubMed ID | 16982858 | Mgi Jnum | J:139334 |
| Mgi Id | MGI:3807759 | Doi | 10.4049/jimmunol.177.7.4262 |
| Citation | Buckler JL, et al. (2006) Cutting edge: T cell requirement for CD28 costimulation is due to negative regulation of TCR signals by PTEN. J Immunol 177(7):4262-6 |
| abstractText | Recent studies suggest that the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) plays a critical role in the maintenance of self-tolerance. Using T cell-specific PTEN knockout mice (PTENDeltaT), we have identified a novel mechanism by which PTEN regulates T cell tolerance. We found that TCR stimulation alone, without CD28 costimulation, is sufficient to induce hyperactivation of the PI3K pathway, which leads to enhanced IL-2 production by naive PTENDeltaT T cells. Importantly, as a result of this increased response to TCR stimulation, PTENDeltaT CD4(+) T cells no longer require CD28 costimulation for in vitro or in vivo expansion. In fact, unlike wild-type T cells, PTENDeltaT CD4(+) T cells are not anergized by delivery of TCR stimulation alone. These data suggest that by negatively regulating TCR signals, PTEN imposes a requirement for CD28 costimulation, thus defining a novel mechanism for its role in self-tolerance. |
