Summary
Antigen-specific effector CD8+ T cells play a critical role in controlling hepatic infections, such as the one caused
by hepatitis B virus (HBV). We review here recent results where we coupled advanced
dynamic imaging with dedicated mouse models of HBV pathogenesis to show that circulating
effector CD8+ T cells aimed at viral clearance initially arrest in liver sinusoids by preferentially
docking onto platelets that have previously adhered to liver sinusoids. Upon detachment
from platelets, effector CD8+ T cells crawl within the sinusoids irrespective of bloodstream direction, and probe
underlying hepatocytes for the presence of antigen by extending filopodia-like protrusions
through the sinusoidal fenestrae. Effector CD8+ T cells recognize hepatocellular antigen and perform effector functions (i.e., IFN-γ
production and hepatocyte killing) while still in the intravascular space. They later
extravasate in the parenchyma. Finally, we provide our perspective on how, in the
next few years, intravital microscopy might shed new light on yet unresolved issues
with particular regard to identifying the determinants of hepatic effector CD8+ T cell trafficking, antigen recognition and effector functions during hepatocellular
carcinoma and understanding the mechanisms whereby intrahepatic T cell priming induces
functionally defective T cell responses. A better understanding of how adaptive immunity
mediates pathogen clearance and tumor elimination may lead to improved vaccination
and treatment strategies for immunotherapy of infectious diseases and cancer.
Keywords
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Article Info
Publication History
Published online: July 13, 2016
Accepted:
July 4,
2016
Received in revised form:
June 30,
2016
Received:
May 4,
2016
Identification
Copyright
© 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
