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10.3390/v10060287

http://scihub22266oqcxt.onion/10.3390/v10060287
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C6024775!6024775!29861472
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suck abstract from ncbi


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pmid29861472      Viruses 2018 ; 10 (6): ä
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  • Histone Modulation Blocks Treg-Induced Foxp3 Binding to the IL-2 Promoter of Virus-Specific CD8+ T Cells from Feline Immunodeficiency Virus-Infected Cats #MMPMID29861472
  • Nag M; Wang Y; De Paris K; E. Fogle J
  • Viruses 2018[Jun]; 10 (6): ä PMID29861472show ga
  • CD8+ T cells are critical for controlling HIV infection. During the chronic phase of lentiviral infection, CD8+ T cells lose their proliferative capacity and exhibit impaired antiviral function. This loss of CD8+ T cell function is due, in part, to CD4+CD25+ T regulatory (Treg) cell-mediated suppression. Our research group has demonstrated that lentivirus-activated CD4+CD25+ Treg cells induce the repressive transcription factor forkhead box P3 (Foxp3) in autologous CD8+ T cells following co-culture. We have recently reported that Treg-induced Foxp3 binds the interleukin-2 (IL-2), interferon-? (IFN- ?), and tumor necrosis factor-? (TNF-?) promoters in virus-specific CD8+ T cells. These data suggest an important role of Foxp3-mediated CD8+ T cell dysfunction in lentiviral infection. To elucidate the mechanism of this suppression, we previously reported that decreased methylation facilitates Foxp3 binding in mitogen-activated CD8+ T cells from feline immunodeficiency virus (FIV)-infected cats. We demonstrated the reduced binding of Foxp3 to the IL-2 promoter by increasing methylation of CD8+ T cells. In the studies presented here, we ask if another form of epigenetic modulation might alleviate Foxp3-mediated suppression in CD8+ T cells. We hypothesized that decreasing histone acetylation in virus-specific CD8+ T cells would decrease Treg-induced Foxp3 binding to the IL-2 promoter. Indeed, using anacardic acid (AA), a known histone acetyl transferase (HAT) inhibitor, we demonstrate a reduction in Foxp3 binding to the IL-2 promoter in virus-specific CD8+ T cells co-cultured with autologous Treg cells. These data identify a novel mechanism of Foxp3-mediated CD8+ T cell dysfunction during lentiviral infection.
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