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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Harland KL,Day EB,Apte SH,Russ BE,Doherty PC,Turner SJ,Kelso Adoi
10.1038/ncomms4547subject
Has Abstractpub_date
2014-03-28 00:00:00pages
3547issn
2041-1723pii
ncomms4547journal_volume
5pub_type
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