HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Related articles in The JI Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chappell, C. Articles by Jacob, J. Search for Related Content PubMed PubMed Citation Articles by Chappell, C. Articles by Jacob, J. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene

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.

Related articles in The JI:

IN THIS ISSUE

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

This article has been cited by other articles:

				R. M. Thomas, N. Chunder, C. Chen, S. E. Umetsu, S. Winandy, and A. D. Wells Ikaros Enforces the Costimulatory Requirement for IL2 Gene Expression and Is Required for Anergy Induction in CD4+ T Lymphocytes J. Immunol., December 1, 2007; 179(11): 7305 - 7315. [Abstract] [Full Text] [PDF]