The loss of TET2 promotes CD8+ T cell memory differentiation

SA Carty, M Gohil, LB Banks, RM Cotton… - The Journal of …, 2018 - journals.aai.org
SA Carty, M Gohil, LB Banks, RM Cotton, ME Johnson, E Stelekati, AD Wells, EJ Wherry
The Journal of Immunology, 2018journals.aai.org
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 …
Abstract
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.
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