Epigenetic plasticity of Cd8a locus during CD8 + T-cell development and effector differentiation and reprogramming

Kim L Harland, E Bridie Day, Simon H. Apte, Brendan E. Russ, Peter C Doherty, Stephen J. Turner, Anne Kelso

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Modulation of CD8 coreceptor levels can profoundly affect T-cell sensitivity to antigen. Here we show that the heritable downregulation of CD8 during type 2 polarization of murine CD8 + effector T cells in vitro and in vivo is associated with CpG methylation of several regions of the Cd8a locus. These epigenetic modifications are maintained long-term in vivo following adoptive transfer. Even after extended type 2 polarization, however, some CD8 low effector cells respond to interferon-I 3 by re-expressing CD8 and a type 1 cytokine profile in association with partial Cd8a demethylation. Cd8a methylation signatures in naive, polarized and repolarized cells are distinct from those observed during the initiation, maintenance and silencing of CD8 expression by developing T cells in the thymus. This persistent capacity for epigenetic reprogramming of coreceptor levels on effector CD8 + T cells enables the heritable tuning of antigen sensitivity in parallel with changes in type 1/type 2 cytokine balance.

Original languageEnglish
Article number3547
Number of pages13
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 28 Mar 2014
Externally publishedYes

Cite this

@article{50ca65da15bb410d958ad7ea3efe00f2,
title = "Epigenetic plasticity of Cd8a locus during CD8 + T-cell development and effector differentiation and reprogramming",
abstract = "Modulation of CD8 coreceptor levels can profoundly affect T-cell sensitivity to antigen. Here we show that the heritable downregulation of CD8 during type 2 polarization of murine CD8 + effector T cells in vitro and in vivo is associated with CpG methylation of several regions of the Cd8a locus. These epigenetic modifications are maintained long-term in vivo following adoptive transfer. Even after extended type 2 polarization, however, some CD8 low effector cells respond to interferon-I 3 by re-expressing CD8 and a type 1 cytokine profile in association with partial Cd8a demethylation. Cd8a methylation signatures in naive, polarized and repolarized cells are distinct from those observed during the initiation, maintenance and silencing of CD8 expression by developing T cells in the thymus. This persistent capacity for epigenetic reprogramming of coreceptor levels on effector CD8 + T cells enables the heritable tuning of antigen sensitivity in parallel with changes in type 1/type 2 cytokine balance.",
author = "Harland, {Kim L} and Day, {E Bridie} and Apte, {Simon H.} and Russ, {Brendan E.} and Doherty, {Peter C} and Turner, {Stephen J.} and Anne Kelso",
year = "2014",
month = "3",
day = "28",
doi = "10.1038/ncomms4547",
language = "English",
volume = "5",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",

}

Epigenetic plasticity of Cd8a locus during CD8 + T-cell development and effector differentiation and reprogramming. / Harland, Kim L; Day, E Bridie; Apte, Simon H.; Russ, Brendan E.; Doherty, Peter C; Turner, Stephen J.; Kelso, Anne.

In: Nature Communications, Vol. 5, 3547, 28.03.2014.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Epigenetic plasticity of Cd8a locus during CD8 + T-cell development and effector differentiation and reprogramming

AU - Harland, Kim L

AU - Day, E Bridie

AU - Apte, Simon H.

AU - Russ, Brendan E.

AU - Doherty, Peter C

AU - Turner, Stephen J.

AU - Kelso, Anne

PY - 2014/3/28

Y1 - 2014/3/28

N2 - Modulation of CD8 coreceptor levels can profoundly affect T-cell sensitivity to antigen. Here we show that the heritable downregulation of CD8 during type 2 polarization of murine CD8 + effector T cells in vitro and in vivo is associated with CpG methylation of several regions of the Cd8a locus. These epigenetic modifications are maintained long-term in vivo following adoptive transfer. Even after extended type 2 polarization, however, some CD8 low effector cells respond to interferon-I 3 by re-expressing CD8 and a type 1 cytokine profile in association with partial Cd8a demethylation. Cd8a methylation signatures in naive, polarized and repolarized cells are distinct from those observed during the initiation, maintenance and silencing of CD8 expression by developing T cells in the thymus. This persistent capacity for epigenetic reprogramming of coreceptor levels on effector CD8 + T cells enables the heritable tuning of antigen sensitivity in parallel with changes in type 1/type 2 cytokine balance.

AB - Modulation of CD8 coreceptor levels can profoundly affect T-cell sensitivity to antigen. Here we show that the heritable downregulation of CD8 during type 2 polarization of murine CD8 + effector T cells in vitro and in vivo is associated with CpG methylation of several regions of the Cd8a locus. These epigenetic modifications are maintained long-term in vivo following adoptive transfer. Even after extended type 2 polarization, however, some CD8 low effector cells respond to interferon-I 3 by re-expressing CD8 and a type 1 cytokine profile in association with partial Cd8a demethylation. Cd8a methylation signatures in naive, polarized and repolarized cells are distinct from those observed during the initiation, maintenance and silencing of CD8 expression by developing T cells in the thymus. This persistent capacity for epigenetic reprogramming of coreceptor levels on effector CD8 + T cells enables the heritable tuning of antigen sensitivity in parallel with changes in type 1/type 2 cytokine balance.

UR - http://www.scopus.com/inward/record.url?scp=84897459921&partnerID=8YFLogxK

U2 - 10.1038/ncomms4547

DO - 10.1038/ncomms4547

M3 - Article

VL - 5

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 3547

ER -