title: Dynamic decrease in PD-1 expression correlates with HBV-specific memory CD8 T-cell development in acute self-limited hepatitis B patients.
abstract: OBJECTIVE
  Programmed death-1 (PD-1) upregulation can impair virus-specific CD8 T-cell responses during chronic viral infection. Whether and how PD-1 affects virus-specific memory CD8 T cells in humans with acute viral infection, however, remains largely undefined.
  
  
  METHODS
  The association between PD-1 expression and HBV-specific memory CD8 T-cell responses were longitudinally analyzed in eighteen patients with acute hepatitis B virus (HBV) infection, including ten patients with human leucocyte antigen (HLA)-A201 and eight with other HLA-A2 subtypes.
  
  
  RESULTS
  At clinical onset, PD-1 was significantly up-regulated and subsequently led to the functional suppression of HBV-specific effector CD8 T cells, as blocking PD-1/PD-L1 interactions in vitro enhanced their proliferation and IFN-gamma production. Following disease resolution, HBV-specific effector CD8 T cells developed into memory T cells. During this period, the dynamic PD-1 decrease was numerically correlated with the reduction of HBV-specific CD8 T-cell frequency, phenotypically with an acquisition of CCR7, CD45RA and CD127 expressions, and functionally with the increase in proliferation and IFN-gamma production of the memory T cells.
  
  
  CONCLUSIONS
  PD-1-mediated inhibitory signaling not only attenuates HBV-specific CD8 T-cell effector function during the acute phase of infection but also correlates with the development of HBV-specific memory CD8 T cells following disease resolution.
authors.affiliation: Research Centre for Biological Therapy, Beijing Institute of Infectious Diseases, Beijing 302 Hospital, 100 Xi Si Huan Middle Road, Beijing 100039, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Jin
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Huifen
authors.initials: H
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Shi
authors.forename: E John
authors.initials: EJ
authors.lastname: Wherry
authors.forename: George K K
authors.initials: GK
authors.lastname: Lau
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D000208:Acute Disease; D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology*; D000956:Antigens, Viral / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D049109:Cell Proliferation; D000939:Epitopes / Q000235:genetics; D005260:Female; D015870:Gene Expression; D015234:HLA-A Antigens / Q000235:genetics; D015789:HLA-A2 Antigen / Q000235:genetics; D006509:Hepatitis B / Q000276:immunology* / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D061026:Programmed Cell Death 1 Receptor; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D000956:Antigens, Viral; D051017:Apoptosis Regulatory Proteins; D000939:Epitopes; D015234:HLA-A Antigens; C435939:HLA-A*02:01 antigen; D015789:HLA-A2 Antigen; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D007371:Interferon-gamma