| First Author | Chappell C | Year | 2006 |
| Journal | J Immunol | Volume | 176 |
| Issue | 8 | Pages | 4562-72 |
| PubMed ID | 16585546 | Mgi Jnum | J:131165 |
| Mgi Id | MGI:3773100 | Doi | 10.4049/jimmunol.176.8.4562 |
| Citation | Chappell C, et al. (2006) DNA methylation by DNA methyltransferase 1 is critical for effector CD8 T cell expansion. J Immunol 176(8):4562-72 |
| abstractText | Transcriptional silencing mediated by DNA methylation is a critical component of epigenetic regulation during early embryonic development in animals. However, the requirement for DNA methylation during activation and differentiation of mature CD8+ T cells into effector and memory cells is not clear. Using cre-mediated deletion of DNA methyltransferase 1 (Dnmt1) at the time of CD8+ T cell activation, we investigated the obligation for maintaining patterns of DNA methylation during the generation of Ag-specific effector and memory CD8+ T cells in response to acute viral infection of mice with lymphocytic choriomeningitis virus. Dnmt1-/- CD8+ T cells failed to undergo the massive CD8+ T cell expansion characteristic of lymphocytic choriomeningitis virus infection, leading to >80% reductions in Ag-specific effector CD8+ T cells at the height of the response. Despite this, Dnmt1-/- CD8+ T cells efficiently controlled the viral infection. Interestingly, the number of Ag-specific Dnmt1-/- memory CD8+ T cells was moderately reduced compared with the reductions seen at day 8 postinfection. Our data suggest that ablation of Dnmt1 and subsequent DNA methylation affect the finite proliferative potential of Ag-specific CD8+ T cells with moderate effects on their differentiation to effector and memory CD8+ T cells. |
