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- Publisher Website: 10.1097/MCG.0000000000001461
- Scopus: eid_2-s2.0-85121028921
- PMID: 33122602
- WOS: WOS:000725702700008
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Article: Phenotypic Changes of PD-1 and GITR in T Cells Are Associated With Hepatitis B Surface Antigen Seroclearance
Title | Phenotypic Changes of PD-1 and GITR in T Cells Are Associated With Hepatitis B Surface Antigen Seroclearance |
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Authors | |
Keywords | GITR HBV HBsAg PD-1 regulatory T cells |
Issue Date | 2020 |
Publisher | Lippincott Williams & Wilkins. The Journal's web site is located at http://www.jcge.com |
Citation | Journal of Clinical Gastroenterology, 2020, Epub 2020-10-28 How to Cite? |
Abstract | Background:
Regulatory T cells (Tregs) possess hepatitis B virus (HBV)-specific immunoregulatory effects in chronic HBV infection. The role of Tregs in spontaneous seroclearance of hepatitis B surface antigen (HBsAg) remains to be determined.
Methods:
We recruited treatment-naive chronic HBV patients achieving spontaneous HBsAg seroclearance (experimental group) and matched HBsAg-positive controls. Peripheral blood mononuclear cells were isolated using the Ficoll-Paque density gradient centrifugation method. The frequency of Tregs and inhibitory phenotypes and immunoregulatory cytokines of Tregs were detected by flow cytometry.
Results:
Twenty-seven patients with HBsAg seroclearance (mean age: 52.40±6.00 y, 55.6% male) and 27 matched controls were recruited. Median HBsAg and HBV DNA levels in the control group were 2.80 (1.24 to 3.43) and 3.16 (1.68 to 3.85) log IU/mL, respectively. Mean frequencies of Tregs and expressions of FoxP3+ Tregs were comparable in both groups (both P>0.05). The mean expression of programmed death 1 (PD-1) and glucocorticoid-induced TNFR family-related gene (GITR) in total CD4+ T cells were significantly downregulated in the experimental group when compared with the control group (10.62% vs. 13.85%, P=0.003; 16.20% vs. 27.02%, P=0.002, respectively). When compared with the control group, PD-1+CD4+ Tregs expression in the experimental group was significantly downregulated (13.85% vs. 10.62%, P=0.003). A similar phenomenon was noted for GITR+CD8+ Tregs (20.16% vs. 14.08%, P=0.049). Intracellular cytokine productions showed no significant differences (all P>0.05).
Conclusions:
The reduced expression of PD-1 and GITR might attenuate the immunosuppressive capability of Tregs. Decreased expression on CD4+ T cells might represent an enhanced antiviral function, playing a role in initiating the “functional cure” of chronic HBV infection. |
Persistent Identifier | http://hdl.handle.net/10722/293677 |
ISSN | 2023 Impact Factor: 2.8 2023 SCImago Journal Rankings: 0.906 |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | LIU, F | - |
dc.contributor.author | ZHANG, S | - |
dc.contributor.author | Wong, DKH | - |
dc.contributor.author | Huang, FY | - |
dc.contributor.author | Cheung, KS | - |
dc.contributor.author | Mak, LY | - |
dc.contributor.author | Fung, J | - |
dc.contributor.author | Yuen, MF | - |
dc.contributor.author | Seto, WK | - |
dc.date.accessioned | 2020-11-23T08:20:13Z | - |
dc.date.available | 2020-11-23T08:20:13Z | - |
dc.date.issued | 2020 | - |
dc.identifier.citation | Journal of Clinical Gastroenterology, 2020, Epub 2020-10-28 | - |
dc.identifier.issn | 0192-0790 | - |
dc.identifier.uri | http://hdl.handle.net/10722/293677 | - |
dc.description.abstract | Background: Regulatory T cells (Tregs) possess hepatitis B virus (HBV)-specific immunoregulatory effects in chronic HBV infection. The role of Tregs in spontaneous seroclearance of hepatitis B surface antigen (HBsAg) remains to be determined. Methods: We recruited treatment-naive chronic HBV patients achieving spontaneous HBsAg seroclearance (experimental group) and matched HBsAg-positive controls. Peripheral blood mononuclear cells were isolated using the Ficoll-Paque density gradient centrifugation method. The frequency of Tregs and inhibitory phenotypes and immunoregulatory cytokines of Tregs were detected by flow cytometry. Results: Twenty-seven patients with HBsAg seroclearance (mean age: 52.40±6.00 y, 55.6% male) and 27 matched controls were recruited. Median HBsAg and HBV DNA levels in the control group were 2.80 (1.24 to 3.43) and 3.16 (1.68 to 3.85) log IU/mL, respectively. Mean frequencies of Tregs and expressions of FoxP3+ Tregs were comparable in both groups (both P>0.05). The mean expression of programmed death 1 (PD-1) and glucocorticoid-induced TNFR family-related gene (GITR) in total CD4+ T cells were significantly downregulated in the experimental group when compared with the control group (10.62% vs. 13.85%, P=0.003; 16.20% vs. 27.02%, P=0.002, respectively). When compared with the control group, PD-1+CD4+ Tregs expression in the experimental group was significantly downregulated (13.85% vs. 10.62%, P=0.003). A similar phenomenon was noted for GITR+CD8+ Tregs (20.16% vs. 14.08%, P=0.049). Intracellular cytokine productions showed no significant differences (all P>0.05). Conclusions: The reduced expression of PD-1 and GITR might attenuate the immunosuppressive capability of Tregs. Decreased expression on CD4+ T cells might represent an enhanced antiviral function, playing a role in initiating the “functional cure” of chronic HBV infection. | - |
dc.language | eng | - |
dc.publisher | Lippincott Williams & Wilkins. The Journal's web site is located at http://www.jcge.com | - |
dc.relation.ispartof | Journal of Clinical Gastroenterology | - |
dc.rights | This is a non-final version of an article published in final form in (provide complete journal citation) | - |
dc.subject | GITR | - |
dc.subject | HBV | - |
dc.subject | HBsAg | - |
dc.subject | PD-1 | - |
dc.subject | regulatory T cells | - |
dc.title | Phenotypic Changes of PD-1 and GITR in T Cells Are Associated With Hepatitis B Surface Antigen Seroclearance | - |
dc.type | Article | - |
dc.identifier.email | Wong, DKH: danywong@hku.hk | - |
dc.identifier.email | Huang, FY: fungyu@hkucc.hku.hk | - |
dc.identifier.email | Cheung, KS: cks634@hku.hk | - |
dc.identifier.email | Mak, LY: lungyi@hku.hk | - |
dc.identifier.email | Fung, J: jfung@hkucc.hku.hk | - |
dc.identifier.email | Yuen, MF: mfyuen@hku.hk | - |
dc.identifier.email | Seto, WK: wkseto@hku.hk | - |
dc.identifier.authority | Wong, DKH=rp00492 | - |
dc.identifier.authority | Cheung, KS=rp02532 | - |
dc.identifier.authority | Mak, LY=rp02668 | - |
dc.identifier.authority | Fung, J=rp00518 | - |
dc.identifier.authority | Yuen, MF=rp00479 | - |
dc.identifier.authority | Seto, WK=rp01659 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1097/MCG.0000000000001461 | - |
dc.identifier.pmid | 33122602 | - |
dc.identifier.scopus | eid_2-s2.0-85121028921 | - |
dc.identifier.hkuros | 318763 | - |
dc.identifier.volume | Epub 2020-10-28 | - |
dc.identifier.isi | WOS:000725702700008 | - |
dc.publisher.place | United States | - |