In:
European Journal of Immunology, Wiley, Vol. 43, No. 3 ( 2013-03), p. 793-804
Abstract:
Cytokine memory for IFN ‐γ production by effector/memory T h1 cells plays a key role in both protective and pathological immune responses. To understand the epigenetic mechanism determining the ontogeny of effector/memory T h1 cells characterized by stable effector functions, we identified a T ‐cell‐specific methylation pattern at the IFNG promoter and CNS ‐1 in ex vivo effector/memory T h1 cells, and investigated methylation dynamics of these regions during the development of effector/memory T h1 cells. During T h1 differentiation, demethylation occurred at both the promoter and CNS ‐1 regions of IFNG as early as 16 h, and this process was independent of cell proliferation and DNA synthesis. Using an IFN ‐γ capture assay, we found early IFN ‐γ‐producing cells from 2‐day differentiating cultures acquired “permissive” levels of demethylation and developed into effector/memory T h1 cells undergoing progressive demethylation at the IFNG promoter and CNS ‐1 when induced by IL ‐12. Methylation levels of these regions in effector/memory T h1 cells of peripheral blood from rheumatoid arthritis patients correlated inversely with reduced frequencies of IFN ‐γ‐producers, coincident with recruitment of effector/memory T h1 cells to the site of inflammation. Thus, after termination of TCR stimulation, IL ‐12 signaling potentiates the stable functional IFN ‐γ memory in effector/memory T h1 cells characterized by hypomethylation at the IFNG promoter and CNS ‐1.
Type of Medium:
Online Resource
ISSN:
0014-2980
,
1521-4141
DOI:
10.1002/eji.201242858
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
1491907-2
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