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 language | English |
|---|---|
| Article number | 3547 |
| Number of pages | 13 |
| Journal | Nature Communications |
| Volume | 5 |
| DOIs | |
| Publication status | Published - 28 Mar 2014 |
| Externally published | Yes |
Cite this
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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 journal › Article › Research › peer-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 -