The Loss of TET2 Promotes CD8+ T Cell Memory Differentiation

被引：132

作者：

Carty, Shannon A. ^{[1
,8
,9
]}

Gohil, Mercy ^{[2
]}

Banks, Lauren B. ^{[2
]}

Cotton, Renee M. ^{[3
]}

Johnson, Matthew E. ^{[4
]}

Stelekati, Erietta ^{[5
,6
]}

Wells, Andrew D. ^{[3
,4
,6
]}

Wherry, E. John ^{[5
,6
]}

Koretzky, Gary A. ^{[2
,7
]}

Jordan, Martha S. ^{[3
,6
]}

机构：

[1] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA

[2] Univ Penn, Abramson Family Canc Res Inst, Perelman Sch Med, Philadelphia, PA 19104 USA

[3] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA

[4] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA

[5] Univ Penn, Perelman Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA

[6] Univ Penn, Perelman Sch Med, Inst Immunol, Philadelphia, PA 19104 USA

[7] Weill Cornell Med, Dept Med, New York, NY 10065 USA

[8] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA

[9] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

来源：

JOURNAL OF IMMUNOLOGY | 2018年 / 200卷 / 01期

基金：

美国国家卫生研究院;

关键词：

HEMATOPOIETIC STEM-CELLS; DNA METHYLATION; 5-METHYLCYTOSINE OXIDATION; SELF-RENEWAL; CLONAL HEMATOPOIESIS; CD8+T CELLS; EFFECTOR; GENERATION; TRANSCRIPTION; EXPRESSION;

D O I：

10.4049/jimmunol.1700559

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

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-deficientmemory CD8(+) T cells demonstrate superior pathogen control. Genome-wide methylation analysis identified a number of differentially methylated regions in TET2-deficient versus wildtype 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.

引用

页码：82 / 91

页数：10

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