Dynamic decrease in PD-1 expression correlates with HBV-specific memory CD8 T-cell development in acute self-limited hepatitis B patients.
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.
Zhang
Zheng
Z
Research Centre for Biological Therapy, Beijing Institute of Infectious Diseases, Beijing 302 Hospital, 100 Xi Si Huan Middle Road, Beijing 100039, China.
Jin
Bo
B
Zhang
Ji-Yuan
JY
Xu
Bin
B
Wang
Huifen
H
Shi
Ming
M
Wherry
E John
EJ
Lau
George K K
GK
Wang
Fu-Sheng
FS
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
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