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575
Immune Cellular Effectors Required for the
Clearances of Different Circulating and
Intrahepatic HBV Antigens
Dan Zhu1, Jia Liu2 and Dongliang Yang2, (1)Department
of Infectious Disease, Union Hosipital,Tongji Medical
College,Huazhong University of Science and Technology,
(2)Department of Infectious Disease, Union Hospital, Tongji
Medical College, Huazhong University of Science and
Technology
Background: Both HBsAg and HBeAg serve as important
serologic markers for the diagnosis and monitoring of patients
with chronic hepatitis B. A cure for HBV infection is most
specifically indicated by HBsAg seroconversion, which usually
occurs later than HBeAg seroconversion. In clinical practice,
however, some patients with HBsAg seroconversion were
found to be persistently positive for circulating HBeAg and
HBV DNA, as well as intrahepatic HBV antigens and DNA.
These observations suggest that different immune effectors
are responsible for the clearances of different circulating and
intrahepatic HBV antigens Methods: To better define the
possible mechanisms, the clearances of HBsAg, HBeAg,
HBcAg and HBV DNA in the serum and liver were studied in
mice that were temporarily depleted a panel of immune cells and
challenged with HBV through hydrodynamic injection (HDI).
Results: We could demonstrate that in the HBV HDI mouse
model, serum HBV DNA clearance is associated with serum
HBeAg clearance but not HBsAg seroconversion. Intrahepatic
HBsAg remains positive after HBsAg seroconversion, while
the clearances of intrahepatic HBcAg and serum HBeAg are
synchronous. Depletion of CD8 T cells resulted in persistence
of serum HBeAg and HBV DNA, but only a slight delay of
HBsAg seroconversion. In contrast, depletion of CD4 T cells
or B cells resulted in persistence of serum HBsAg, HBeAg
and HBV DNA. Interestingly, clearance of intrahepatic HBsAg
but not HBcAg was observed in B cell depleted mice, although
they remained serum HBsAg positive at the corresponding
time point. To further examine the function of CD8 T cells and
B cells in mediating serum HBsAg and HBeAg, purified CD8
T cells and non-CD8 splenocytes (about 60% of which are B
cells) from HBV resolved mice were adoptively transferred to
naive mice. CD8 T cells preferentially infiltrated into the liver
while B cells preferentially infiltrated into the spleen. After HBV
challenge, CD8 T cell transferred mice showed significantly
accelerated serum HBeAg clearance and non-CD8
splenocyte transferred mice showed significantly accelerated
serum HBsAg clearance. Conclusion: Taken together, these
results reveal that CD8+ T cells are not essential cellular
effector for circulating HBsAg clearance. Both CD4 T cells
and B cells serve as master effectors for circulating HBsAg,
HBeAg and HBV DNA clearances. The role and mechanism
of B cells in mediating intrahepatic HBV clearance remains to
be thoroughly explored.
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发表于 2018-10-26 15:08