alexa Cutting edge: Prolonged exposure to HIV reinforces a poised epigenetic program for PD-1 expression in virus-specific CD8 T cells.
Immunology

Immunology

Immunotherapy: Open Access

Author(s): Youngblood B, Noto A, Porichis F, Akondy RS, Ndhlovu ZM, , Youngblood B, Noto A, Porichis F, Akondy RS, Ndhlovu ZM, , Youngblood B, Noto A, Porichis F, Akondy RS, Ndhlovu ZM, , Youngblood B, Noto A, Porichis F, Akondy RS, Ndhlovu ZM,

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Abstract Ag-specific CD8 T cells play a critical role in controlling HIV infection but eventually lose antiviral functions in part because of expression and signaling through the inhibitory programmed death-1 (PD-1) receptor. To better understand the impact of prolonged TCR ligation on regulation of PD-1 expression in HIV-specific CD8 T cells, we investigated the capacity of virus-specific CD8 T cells to modify the PD-1 epigenetic program after reduction in viral load. We observed that the transcriptional regulatory region was unmethylated in the PD-1(hi) HIV-specific CD8 T cells, whereas it remained methylated in donor-matched naive cells at acute and chronic stages of infection. Surprisingly, the PD-1 promoter remained unmethylated in HIV-specific CD8 T cells from subjects with a viral load controlled by antiviral therapy for >2 y or from elite controllers. Together, these data demonstrate that the epigenetic program at the PD-1 locus becomes fixed after prolonged exposure to HIV virus.
This article was published in J Immunol and referenced in Immunotherapy: Open Access

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