| First Author | Singh N | Year | 2010 |
| Journal | Eur J Immunol | Volume | 40 |
| Issue | 2 | Pages | 559-68 |
| PubMed ID | 19950180 | Mgi Jnum | J:157784 |
| Mgi Id | MGI:4436967 | Doi | 10.1002/eji.200939736 |
| Citation | Singh N, et al. (2010) Defective T-cell receptor-induced apoptosis of T cells and rejection of transplanted immunogenic tumors in p53(-/-) mice. Eur J Immunol 40(2):559-68 |
| abstractText | Mice lacking the tumor suppressor gene p53 spontaneously develop T-cell lymphomas at a high rate, suggesting that in these mice lymphomas arise due to defective apoptosis mechanisms in T cells mediated by p53. However, a role of p53 in regulation of T-cell responses or apoptosis has been poorly defined. TCR-mediated signaling in the absence of CD28 costimulation induces both apoptosis and proliferation of naive T cells from WT mice. In this report we show that, in response to TCR stimulation, T cells from naive p53-deficient mice exhibited higher proliferation and drastically reduced apoptosis than WT T cells. CD28 costimulation enhanced the proliferation of TCR-stimulated WT and p53(-/-) T cells, suggesting that p53 uncouples CD28-mediated antiapoptotic and proliferative signals. To evaluate the physiological significance of these findings, we transplanted OVA expressing-EG.7 tumor cells into WT and p53(-/-) mice. Unlike WT mice, p53(-/-) mice exhibited a robust tumor-resistant phenotype and developed cytotoxic T-cell responses against OVA. Collectively, these data support the hypothesis that p53 is an essential factor in negative regulation of T-cell responses and have implication for immunomodulation during treatment of cancers and other inflammatory conditions. |
