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2015 ; 5
(ä): 12159
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Regulation of T cell function by microRNA-720
#MMPMID26199080
Wang Y
; Zhang Z
; Ji D
; Chen GF
; Feng X
; Gong LL
; Guo J
; Li ZW
; Chen CF
; Zhao BB
; Li ZG
; Li QJ
; Yan HP
; Sempowski G
; Wang FS
; He YW
Sci Rep
2015[Jul]; 5
(ä): 12159
PMID26199080
show ga
Chronic hepatitis B virus (HBV) infection is a major global health burden.
Functional exhaustion and numerical reduction of HBV-specific cytotoxic T
lymphocytes (CTLs) in the liver and peripheral blood limit anti-HBV CTL activity
in patients with chronic HBV infection (CHB). However, the ongoing anti-HBV
CD8(+) T cell responses in the lymphoid organs are largely unknown due to the
infeasibility of obtaining lymphoid organs from CHB patients. Here we demonstrate
that the percentage of HBV-specific CD8(+) T cells is higher in the spleen of CHB
patients than that from peripheral blood and liver. Although they do respond to
TCR stimulation and produce IFN?, the cells proliferate poorly. Furthermore,
miR-720 expression is upregulated in HBV-specific CD8(+) T cells. Overexpression
of miR-720 in primary human CD8(+) T cells inhibits TCR stimulation-induced
proliferation. We also demonstrate that TGF? sustains miR-720 upregulation after
TCR stimulation, and blood TGF? levels are associated with the outcome of type I
interferon treatment of CHB patients. Thus, therapies targeting miR-720 may help
restore impaired immunity in CHB patients.
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