Hepatitis C virus core protein reduces CD 8 + T‐cell proliferation, perforin production and degranulation but increases STAT 5 activation
Clearance of hepatitis C virus ( HCV ) is dependent on an effective virus‐specific CD 8 + T‐cell response, which is dysfunctional in chronic HCV infection. Dysfunction in bulk or non‐ HCV ‐specific CD 8 + T‐cells in HCV infection has also been observed. This may contribute to observed reductions in...
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Veröffentlicht in: | Immunology 2018-05, Vol.154 (1), p.156-165 |
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Sprache: | eng |
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Zusammenfassung: | Clearance of hepatitis C virus (
HCV
) is dependent on an effective virus‐specific
CD
8
+
T‐cell response, which is dysfunctional in chronic
HCV
infection. Dysfunction in bulk or non‐
HCV
‐specific
CD
8
+
T‐cells in
HCV
infection has also been observed. This may contribute to observed reductions in immunity to other diseases (e.g. cancer, viral co‐infections) in
HCV
‐infected individuals. Evidence suggests that the
HCV
core protein (found in blood as free protein) may contribute to this impairment. To determine if
HCV
core contributes to the impairment of effector functions and survival potential of
CD
8
+
T‐cells, isolated human
CD
8
+
T‐cells from healthy donors were pre‐incubated with recombinant
HCV
core protein for 72 hr and then stimulated
in vitro
to evaluate proliferation, survival potential and effector functions. Pre‐incubation of stimulated
CD
8
+
T‐cells with
HCV
core significantly reduced their proliferation. Perforin production and degranulation were also decreased, but interferon‐
γ
production was unchanged. Additionally, when
CD
8
+
T‐cells were treated with serum from
HCV
+
individuals, they produced less perforin than cells treated with healthy serum. Up‐regulation of anti‐apoptotic Bcl‐2 was slightly lower in cells treated with
HCV
core, but signal transducer and activator of transcription 5 (
STAT
5) activation was increased, suggesting dysregulation downstream of
STAT
activation. Our study reveals that
HCV
core reduces the activity and target lysis‐associated functions of
CD
8
+
T‐cells. This may contribute to the generalized impairment of
CD
8
+
T‐cells observed in
HCV
infection. These findings provide insight for the design of novel counteractive immune‐mediated strategies including the design of effective therapeutic vaccines for use in
HCV
+
individuals. |
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ISSN: | 0019-2805 1365-2567 |
DOI: | 10.1111/imm.12882 |