Decrease of T-cells exhaustion markers programmed cell death-1 and T-cell immunoglobulin and mucin domain-containing protein 3 and plasma IL-10 levels ... View Full Text


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Article Info

DATE

2020-09-29

AUTHORS

Sylwia Osuch, Tomasz Laskus, Hanna Berak, Karol Perlejewski, Karin J. Metzner, Marcin Paciorek, Marek Radkowski, Kamila Caraballo Cortés

ABSTRACT

During chronic hepatitis C virus (HCV) infection, both CD4+ and CD8+ T-cells become functionally exhausted, which is reflected by increased expression of programmed cell death-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), and elevated anti-inflammatory interleukin 10 (IL-10) plasma levels. We studied 76 DAA-treated HCV-positive patients and 18 non-infected controls. Flow cytometry measured pretreatment frequencies of CD4+PD-1+, CD4+PD-1+Tim-3+ and CD8+PD-1+Tim-3+ T-cells and IL-10 levels measured by ELISA were significantly higher and CD4+PD-1-Tim-3- and CD8+PD-1-Tim-3- T-cells were significantly lower in patients than in controls. Treatment resulted in significant decrease of CD4+Tim-3+, CD8+Tim-3+, CD4+PD-1+Tim-3+ and CD8+PD-1+Tim-3+ T-cell frequencies as well as IL-10 levels and increase in CD4+PD-1-Tim-3- and CD8+PD-1-Tim-3- T-cells. There were no significant changes in the frequencies of CD4+PD-1+ T-cells, while CD8+PD-1+ T-cells increased. Patients with advanced liver fibrosis had higher PD-1 and lower Tim-3 expression on CD4+T-cells and treatment had little or no effect on the exhaustion markers. HCV-specific CD8+T-cells frequency has declined significantly after treatment, but their PD-1 and Tim-3 expression did not change. Successful treatment of chronic hepatitis C with DAA is associated with reversal of immune exhaustion phenotype, but this effect is absent in patients with advanced liver fibrosis. More... »

PAGES

16060

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-020-73137-6

DOI

http://dx.doi.org/10.1038/s41598-020-73137-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1131253241

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/32994477


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37 schema:description During chronic hepatitis C virus (HCV) infection, both CD4<sup>+</sup> and CD8<sup>+</sup> T-cells become functionally exhausted, which is reflected by increased expression of programmed cell death-1 (PD-1) and T-cell immunoglobulin and mucin domain-containing protein 3 (Tim-3), and elevated anti-inflammatory interleukin 10 (IL-10) plasma levels. We studied 76 DAA-treated HCV-positive patients and 18 non-infected controls. Flow cytometry measured pretreatment frequencies of CD4<sup>+</sup>PD-1<sup>+</sup>, CD4<sup>+</sup>PD-1<sup>+</sup>Tim-3<sup>+</sup> and CD8<sup>+</sup>PD-1<sup>+</sup>Tim-3<sup>+</sup> T-cells and IL-10 levels measured by ELISA were significantly higher and CD4<sup>+</sup>PD-1<sup>-</sup>Tim-3<sup>-</sup> and CD8<sup>+</sup>PD-1<sup>-</sup>Tim-3<sup>-</sup> T-cells were significantly lower in patients than in controls. Treatment resulted in significant decrease of CD4<sup>+</sup>Tim-3<sup>+</sup>, CD8<sup>+</sup>Tim-3<sup>+</sup>, CD4<sup>+</sup>PD-1<sup>+</sup>Tim-3<sup>+</sup> and CD8<sup>+</sup>PD-1<sup>+</sup>Tim-3<sup>+</sup> T-cell frequencies as well as IL-10 levels and increase in CD4<sup>+</sup>PD-1<sup>-</sup>Tim-3<sup>-</sup> and CD8<sup>+</sup>PD-1<sup>-</sup>Tim-3<sup>-</sup> T-cells. There were no significant changes in the frequencies of CD4<sup>+</sup>PD-1<sup>+</sup> T-cells, while CD8<sup>+</sup>PD-1<sup>+</sup> T-cells increased. Patients with advanced liver fibrosis had higher PD-1 and lower Tim-3 expression on CD4<sup>+</sup>T-cells and treatment had little or no effect on the exhaustion markers. HCV-specific CD8<sup>+</sup>T-cells frequency has declined significantly after treatment, but their PD-1 and Tim-3 expression did not change. Successful treatment of chronic hepatitis C with DAA is associated with reversal of immune exhaustion phenotype, but this effect is absent in patients with advanced liver fibrosis.
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44 schema:keywords C virus (HCV) infection
45 CD4
46 CD8
47 DAA
48 ELISA
49 HCV-positive patients
50 HCV-specific CD8
51 IL-10 levels
52 PD-1
53 Tim-3
54 Tim-3 expression
55 advanced liver fibrosis
56 anti-inflammatory interleukin 10 (IL-10) plasma levels
57 cell death 1
58 cell exhaustion markers
59 cell frequencies
60 cell immunoglobulin
61 cells
62 changes
63 chronic hepatitis C
64 chronic hepatitis C virus (HCV) infection
65 control
66 cytometry
67 death-1
68 decrease
69 domain-containing protein 3
70 effect
71 exhaustion markers
72 exhaustion phenotype
73 expression
74 fibrosis
75 frequency
76 frequency of CD4
77 hepatitis C
78 hepatitis C virus infection
79 high PD-1
80 immune exhaustion phenotype
81 immunoglobulin
82 increase
83 increased expression
84 infection
85 interleukin-10 plasma levels
86 levels
87 liver fibrosis
88 lower Tim-3 expression
89 markers
90 mucin domain-containing protein 3
91 non-infected controls
92 patients
93 phenotype
94 plasma levels
95 pretreatment frequency
96 protein 3
97 reversal
98 significant changes
99 significant decrease
100 successful treatment
101 treatment
102 virus infection
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