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DNA Methylation by DNA Methyltransferase 1 Is Critical for Effector CD8 T Cell Expansion¹

Craig Chappell^*, Caroline Beard, John Altman^*, Rudolph Jaenisch^, and Joshy Jacob^2,*

^* Emory Vaccine Center, Department of Microbiology and Immunology, Emory University, Atlanta, GA 30329; and Whitehead Institute for Biomedical Research and Biology Department, Massachusetts Institute of Technology, Cambridge, MA 02139

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.

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The JI 2006 176: 4507-4508. [Full Text]  

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