The Loss of TET2 Promotes CD8 + T Cell Memory Differentiation

T cell differentiation requires appropriate regulation of DNA methylation. In this article, we demonstrate that the methylcytosine dioxygenase ten-eleven translocation (TET)2 regulates CD8 T cell differentiation. In a murine model of acute viral infection, TET2 loss promotes early acquisition of a m...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2018-01, Vol.200 (1), p.82-91
Main Authors: Carty, Shannon A, Gohil, Mercy, Banks, Lauren B, Cotton, Renee M, Johnson, Matthew E, Stelekati, Erietta, Wells, Andrew D, Wherry, E John, Koretzky, Gary A, Jordan, Martha S
Format: Article
Language:English
Subjects:
Animal models
Animals
CD8 antigen
CD8-Positive T-Lymphocytes - immunology
Cell Differentiation
Cell fate
Cell Proliferation
Cells, Cultured
Dioxygenase
DNA Methylation
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Genomes
Immunologic Memory
Immunological memory
Lymphocyte Activation
Lymphocytes
Lymphocytes T
Lymphocytic Choriomeningitis - immunology
Lymphocytic choriomeningitis virus - immunology
Memory cells
Mice
Mice, Inbred C57BL
Mice, Knockout
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - metabolism
T cell receptors
T-Lymphocyte Subsets - immunology
Transcription
Translocation
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Summary:T cell differentiation requires appropriate regulation of DNA methylation. In this article, we demonstrate that the methylcytosine dioxygenase ten-eleven translocation (TET)2 regulates CD8 T cell differentiation. In a murine model of acute viral infection, TET2 loss promotes early acquisition of a memory CD8 T cell fate in a cell-intrinsic manner without disrupting Ag-driven cell expansion or effector function. Upon secondary recall, TET2-deficient memory CD8 T cells demonstrate superior pathogen control. Genome-wide methylation analysis identified a number of differentially methylated regions in TET2-deficient versus wild-type CD8 T cells. These differentially methylated regions did not occur at the loci of differentially expressed memory markers; rather, several hypermethylated regions were identified in known transcriptional regulators of CD8 T cell memory fate. Together, these data demonstrate that TET2 is an important regulator of CD8 T cell fate decisions.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.1700559