Accuri C6 Flow Cytometer System
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0807583

Received for publication August 30, 2007.
Revised May 1, 2008.
Accepted for publication May 5, 2008.

Article

Epigenetic mechanisms of age-dependent KIR2DL4 expression in T cells

Guangjin Li , Cornelia M. Weyand , and Jörg J. Goronzy @

Kathleen B. and Mason I. Lowance Center for Human Immunology, Emory University, Atlanta, Georgia, USA

@ To whom correspondence should be addressed. E-mail: jgoronz{at}emory.edu.


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Abstract

Killer Ig-like receptor (KIR) expression is mostly restricted to NK cells controlling their activation. With increasing age, KIRs are expressed on T cells and contribute to age-related diseases. We examined epigenetic mechanisms that determine the competency of T cells to transcribe KIR2DL4. Compared with Jurkat cells and CD4+CD28+ T cells from young individuals, DNA methyltransferase (DNMT) inhibition was strikingly more effective in T cells from elderly adults and the CD4+CD28– T cell line HUT78 to induce KIR2DL4 transcription. In these susceptible cells, the KIR2DL4 promoter was partially demethylated, and dimethylated H3-Lys 4 was increased, and all other histone modifications were characteristic for an inactive promoter. In comparison, NK cells had a fully demethylated KIR2DL4 promoter and the full spectrum of histone modifications indicative of active transcription with H3 and H4 acetylation, di- and trimethylated H3-Lys 4, and reduced, dimethylated H3-Lys 9. These results suggest that an increased competency of T cells to express KIR2DL4 with aging is conferred by a selective increase in H3-Lys 4 dimethylation and limited DNA demethylation. The partially accessible promoter is sensitive to DNMT inhibition, which is sufficient to induce full transcription without further histone acetylation and methylation.

Key Words: molecular biology of aging • deacetylase • cellular immunology • cellular senescence • gene expression




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