Programmed death-1 (PD-1) is demonstrated to have an increased expression on antigen-specific T cells during chronic virus infections, and the blockage of PD-1/PD-ligand (PD-L1) pathway could restore the function of exhausted T cells. We measured the PD-1 expression levels on HBV-specific CD8 T cells and investigated the role of PD-1/PD-L1 pathway in T-cell responses of patients with different HBV infection statuses. Compared to the patients with convalescent acute hepatitis B, PD-1 expression on total CD8 T cells from chronic hepatitis B (CHB) patients was significantly upregulated, especially on the HBV pentamer-positive CD8 T cells. And PD-L1, but not PD-L2, was also significantly upregulated on PBMC from CHB patients. In CHB patients, HBV-specific T cells and cellular proliferation could be observed under the recombinant HBV-Ag stimulation in vitro, and blockade of PD-1 pathway significantly enhanced the IFN-gamma production and cellular proliferation of PBMC. Furthermore, PD-1 expression level on HBV-pentamers positive CD8 T cells was positively associated with plasma viral load in CHB patients. Thus, PD-1 upregulation on HBV-specific CD8 T cells is engaged in the dysfunction of T cells and high viraemia in CHB patients, and the antiviral T-cell responses could be improved by the blockade of this inhibitory PD-1/PD-L1 pathway. (c) 2007 Elsevier Ltd. All rights reserved.
机构:Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa
Day, Cheryl L.
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Kaufmann, Daniel E.
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Kiepiela, Photini
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Brown, Julia A.
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Reddy, Sharon
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Miller, Joseph D.
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Zhu, Baogong
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机构:Univ KwaZulu Natal, Doris Duke Med Res Inst, HIV Pathogenesis Programme, ZA-4013 Durban, South Africa
Day, Cheryl L.
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Kaufmann, Daniel E.
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Kaufmann, Daniel E.
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Kiepiela, Photini
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Brown, Julia A.
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Brown, Julia A.
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Moodley, Eshia S.
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Moodley, Eshia S.
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Reddy, Sharon
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Miller, Joseph D.
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Zhu, Baogong
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Zhu, Baogong
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Eichbaum, Quentin
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Altfeld, Marcus
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Wherry, E. John
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Coovadia, Hoosen M.
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Ahmed, Rafi
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Ahmed, Rafi
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