17567698

pubmed:Citation

17

Infection with hepatitis C virus (HCV) is associated with persistence in the majority of individuals. We demonstrate here that the inhibitory molecule programmed death-1 (PD-1) is significantly upregulated on total and HCV-specific CD8(+) cytotoxic T lymphocytes (CTLs) in the peripheral blood and livers of patients with chronic infection compared to subjects with spontaneous HCV resolution, patients with nonviral liver disease, and normal controls. PD-1 expression on cytomegalovirus-specific CTLs also varies according to HCV status and is highest in patients with chronic infection. HCV-specific CTLs that are PD-1(high) express higher levels of the senescence marker CD57 than PD-1(low) CTLs, and CD57 expression is greater in chronic than in resolved infection. In vitro blockade of PD-1 by monoclonal antibodies specific to its ligands (PD-L1 and PD-L2) results in restoration of functional competence (proliferation and gamma interferon and interleukin-2 secretion) of HCV-specific CTLs, including those residing in the liver. This reversal of CTL exhaustion is evident even in individuals who lack HCV-specific CD4(+) T-cell help. Our data indicate that the PD-1/PD-L pathway is critical in persistent HCV infection in humans and represents a potential novel target for restoring function of exhausted HCV-specific CTLs.

http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-10358209, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-10581077, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-10847128, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-11244031, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-11356962, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-11870386, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-11927944, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-12218168, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-12526953, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-14734757, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-15122199, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-15486925, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-15771580, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-15919940, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-16107834, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-16382236, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-16469690, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-16500147, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-16724117, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-16845628, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-16876901, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-16917489, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-16921384, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-16954372, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-16956940, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-17000870, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-17058243, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-17151366, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-17182670, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-17326153, http://linkedlifedata.com/resource/pubmed/commentcorrection/17567698-17326154

http://linkedlifedata.com/resource/pubmed/journal/0113724

http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD274, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD57, http://linkedlifedata.com/resource/pubmed/chemical/Apoptosis Regulatory Proteins, http://linkedlifedata.com/resource/pubmed/chemical/CD274 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma, http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2, http://linkedlifedata.com/resource/pubmed/chemical/PDCD1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/PDCD1LG2 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Programmed Cell Death 1 Ligand 2..., http://linkedlifedata.com/resource/pubmed/chemical/Programmed Cell Death 1 Receptor

Sep

pubmed-author:CastelblancoNicoleN, pubmed-author:Golden-MasonLucyL, pubmed-author:KlarquistJaredJ, pubmed-author:MengsholJohn AJA, pubmed-author:PalmerBrentB, pubmed-author:RosenHugo RHR

81

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2011-11-17