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a 271
CXCR5-EXPRESSING CD8+ T CELLS CONTRIBUTE TO HBsAg
CLEARANCE IN CHRONIC HBV INFECTION
Yongyin Li, Libo Tang, Chengcong Chen, Shuqin Gu, Yang
Zhou, Guofu Ye, Xiaoyi Li, Weibin Wang, Jian Sun, Jie Peng
and Jinlin Hou, Department of Infectious Diseases , Nanfang
Hospital, Southern Medical University
Background: CD8+ T cell dysfunction impairs immunemediated
viral control in chronic hepatitis B virus (HBV)
infection, however, the pool of CD8+ T cells is functionally
heterogeneous Therefore, CD8+ T cell subpopulations with
unique properties, particularly those with defining functions,
should be further investigated This study aims to dissect a
subset of CD8+ T cells expressing C-X-C motif chemokine
receptor 5 (CXCR5) in chronic HBV infection. Methods:
The frequency of circulating CXCR5+CD8+ T cells and the
levels of C-X-C motif chemokine ligand 13 (CXCL13) were
measured in chronic hepatitis B (CHB) patients receiving
nucleos(t)ide analogue antiviral therapy A series of surface
markers of peripheral and hepatic CXCR5+ and CXCR5−
CD8+ T cells were assessed, as well as the expression of
intracellular HBV-specific interferon (IFN)-γ or interleukin (IL)-
21. Immunocompetent C57BL/6, IL-21 receptor-deficient or
μMT mice (B cell-deficient) were hydrodynamically injected
with pAAV-HBV1.2 plasmids. Some of the mice were given
an injection of sorted CXCR5+CD8+ or CXCR5−CD8+ T cells
Serum levels of hepatitis B surface antigen (HBsAg) and the
frequency of HBV-specific IFN-γ from peripheral, splenic,
and hepatic CXCR5+CD8+ T cells were assessed Results:
CXCR5+CD8+ T cells were expanded and possessed
distinctive phenotypical and transcriptional properties in
patients with chronic HBV infection (Figure A); moreover,
this subset of CD8+ T cells maintained decent antiviral ability
and was associated with favorable treatment response in
CHB patients (Figure B-D) Although CXCR5+CD8+ T cells
showed higher expression of programmed cell death 1
(PD1) than that of the CXCR5− subset, they demonstrated
a status of activation with memory potential based on their
enhanced expression of CD69 and CD38 as well as CD62L
and CCR7 (Figure E) Notably, high levels of CXCL13 from
patients with HBV infection promoted the recruitment of
intrahepatic CXCR5+CD8+ T cells and were associated with
favorable outcomes (Figure F), and an increased production
of HBV-specific IFN-γ and IL-21 was found in intrahepatic
CXCR5+CD8+ T cells (Figure G and H) More strikingly, mice
with adoptive transfer of CXCR5+CD8+ T cells exhibited a more
potent ability to control HBV replication (Figure I). Additionally,
an impaired production of HBV-specific IFN-γ from hepatic
CXCR5+CD8+ T cells was observed in mice deficient in IL-
21 receptor or in B cells (Figure J and K). Conclusion:
CXCR5+CD8+ T cells demonstrate potent anti-HBV effect
and facilitate HBsAg clearance in chronic HBV infection. The
identification of this unique subpopulation may contribute to
a better understanding of CD8+ T cell functions and provide a
potential immunotherapeutic target for HBV cure. |
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发表于 2019-10-25 17:41