tetano
Editor, Senior Moderator
Nat Commun. 2014 Mar 28;5:3547. doi: 10.1038/ncomms4547.
Epigenetic plasticity of Cd8a locus during CD8(+) T-cell development and effector differentiation and reprogramming.
Harland KL1, Day EB1, Apte SH2, Russ BE3, Doherty PC4, Turner SJ3, Kelso A5.
Author information
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-γ 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.
PMID:
24675400
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/24675400
Epigenetic plasticity of Cd8a locus during CD8(+) T-cell development and effector differentiation and reprogramming.
Harland KL1, Day EB1, Apte SH2, Russ BE3, Doherty PC4, Turner SJ3, Kelso A5.
Author information
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-γ 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.
PMID:
24675400
[PubMed - in process]
http://www.ncbi.nlm.nih.gov/pubmed/24675400