Aberrant production of soluble inducible T cell co‑stimulator and soluble programmed cell death protein 1 in patients with chronic hepatitis B

Wang,Dongsheng; Du,Qin; Luo,Guangcheng; Wang,Qiang; Wang,Guangrong; Zhang,Guoyuan; Leng,Zhengwei; Guo,Xiaolan

doi:10.3892/mmr.2017.7630

Aberrant production of soluble inducible T cell co‑stimulator and soluble programmed cell death protein 1 in patients with chronic hepatitis B

Authors:
- Dongsheng Wang
- Qin Du
- Guangcheng Luo
- Qiang Wang
- Guangrong Wang
- Guoyuan Zhang
- Zhengwei Leng
- Xiaolan Guo
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Affiliations: Department of Laboratory Medicine, The Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan 637000, P.R. China, Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430074, P.R. China
Published online on: September 26, 2017 https://doi.org/10.3892/mmr.2017.7630
Pages: 8556-8562

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Abstract

Previous studies demonstrated that immune dysregulation is an important cause of hepatitis B virus (HBV)‑mediated liver damage. Co‑stimulators including programmed cell death protein 1 (PD‑1) and inducible T cell co‑stimulator (ICOS) are involved in the pathogenesis of HBV. In the present study, the serum levels of soluble (s)PD‑1 and sICOS in patients with chronic HBV infections, were investigated, and the association between sPD‑1 and sICOS levels and liver injury degree was investigated. Serum sPD‑1 and sICOS levels were increased in the HBV‑patient group particularly in the HBV external core antigen positive group. In the immune clearance group, sPD‑1 and sICOS were increased compared with the tolerance group. Furthermore, the relative mRNA expression levels were also increased in patients with HBV. However there was no correlation between sPD‑1 and sICOS levels and HBV antibodies or PD‑1/ICOS mRNA copies. The altered sPD‑1 and sICOS serum levels in the different HBV groups may reflect the dysregulation of T cell activation, and may be associated with the HBV pathological process.

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1	Lok AS: The maze of treatments for hepatitis B. N Engl J Med. 352:2743–2746. 2005. View Article : Google Scholar : PubMed/NCBI
2	Ferrari C: HBV and the immune response. Liver Int. 35 Suppl 1:S121–S128. 2015. View Article : Google Scholar
3	Lee JA, Kim YM, Hyun PM, Jeon JW, Park JK, Suh GH, Jung BG and Lee BJ: Honeybee (Apis mellifera) venom reinforces viral clearance during the early stage of infection with porcine reproductive and respiratory syndrome virus through the up-regulation of Th1-specific immune responses. Toxins (Basel). 7:1837–1853. 2015. View Article : Google Scholar : PubMed/NCBI
4	Klein J and Sato A: The HLA system. First of two parts. N Engl J Med. 343:702–709. 2000. View Article : Google Scholar : PubMed/NCBI
5	Wang D, Zhou D, DU Q, Liang Q, Wang Q, Fang L, Wang G, Fan Q, Liu B, Zhou J, et al: Aberrant production of soluble inducible T-cell co-stimulator (sICOS) and soluble programmed cell death protein 1 (sPD-1) in patients with chronic hepatitis C. Mol Med Rep. 7:1197–1202. 2013. View Article : Google Scholar : PubMed/NCBI
6	Cao J, Zhang L, Huang S, Chen P, Zou L, Chen H, Xiang Y, Lai X and Ren G: Aberrant production of soluble co-stimulatory molecules CTLA-4 and CD28 in patients with chronic hepatitis B. Microb Pathog. 51:262–267. 2011. View Article : Google Scholar : PubMed/NCBI
7	Wang L, Zhao C, Peng Q, Shi J and Gu G: Expression levels of CD28, CTLA-4, PD-1 and Tim-3 as novel indicators of T-cell immune function in patients with chronic hepatitis B virus infection. Biomed Rep. 2:270–274. 2014.PubMed/NCBI
8	Nurieva RI, Mei XM, Forbush K, Bevan MJ and Dong C: B7h is required for T cell activation, differentiation, and effector function. Proc Natl Acad Sci USA. 100:pp. 14163–14168. 2003; View Article : Google Scholar : PubMed/NCBI
9	Yanaba K, Asano Y, Noda S, Akamata K, Aozasa N, Taniguchi T, Takahashi T, Ichimura Y, Toyama T, Sumida H, et al: Increased production of soluble inducible costimulator in patients with diffuse cutaneous systemic sclerosis. Arch Dermatol Res. 305:17–23. 2013. View Article : Google Scholar : PubMed/NCBI
10	Wu X, Zhang H, Xing Q, Cui J, Li J, Li Y, Tan Y and Wang S: PD-1(+) CD8(+) T Cells are exhausted in tumours and functional in draining lymph nodes of colorectal cancer patients. Br J Cancer. 111:1391–1399. 2014. View Article : Google Scholar : PubMed/NCBI
11	Her M, Kim D, Oh M, Jeong H and Choi I: Increased expression of soluble inducible costimulator ligand (ICOSL) in patients with systemic lupus erythematosus. Lupus. 18:501–507. 2009. View Article : Google Scholar : PubMed/NCBI
12	Wan B, Nie H, Liu A, Feng G, He D, Xu R, Zhang Q, Dong C and Zhang JZ: Aberrant regulation of synovial T cell activation by soluble costimulatory molecules in rheumatoid arthritis. J Immunol. 177:8844–8850. 2006. View Article : Google Scholar : PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Method. 25:402–408. 2001. View Article : Google Scholar
14	Ye B, Liu X, Li X, Kong H, Tian L and Chen Y: T-cell exhaustion in chronic hepatitis B infection: Current knowledge and clinical significance. Cell Death Dis. 6:e16942015. View Article : Google Scholar : PubMed/NCBI
15	Bengsch B, Martin B and Thimme R: Restoration of HBV-specific CD8+ T cell function by PD-1 blockade in inactive carrier patients is linked to T cell differentiation. J Hepatol. 61:1212–1219. 2014. View Article : Google Scholar : PubMed/NCBI
16	Magistrelli G, Jeannin P, Elson G, Gauchat JF, Nguyen TN, Bonnefoy JY and Delneste Y: Identification of three alternatively spliced variants of human CD28 mRNA. Biochem Biophys Res Commun. 259:34–37. 1999. View Article : Google Scholar : PubMed/NCBI
17	Hutloff A, Dittrich AM, Beier KC, Eljaschewitsch B, Kraft R, Anagnostopoulos I and Kroczek RA: ICOS is an inducible T-cell co-stimulator structurally and functionally related to CD28. Nature. 397:263–266. 1999. View Article : Google Scholar : PubMed/NCBI
18	Ishida Y, Agata Y, Shibahara K and Honjo T: Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 11:3887–3895. 1992.PubMed/NCBI
19	Jiang W: Blockade of B7-H1 enhances dendritic cell-mediated T cell response and antiviral immunity in HBV transgenic mice. Vaccine. 30:758–766. 2012. View Article : Google Scholar : PubMed/NCBI
20	Shankar EM, Che KF, Messmer D, Lifson JD and Larsson M: Expression of a broad array of negative costimulatory molecules and Blimp-1 in T cells following priming by HIV-1 pulsed dendritic cells. Mol Med. 17:229–240. 2011. View Article : Google Scholar : PubMed/NCBI
21	Cheng HY, Kang PJ, Chuang YH, Wang YH, Jan MC, Wu CF, Lin CL, Liu CJ, Liaw YF, Lin SM, et al: Circulating programmed death-1 as a marker for sustained high hepatitis B viral load and risk of hepatocellular carcinoma. PLoS One. 9:e958702014. View Article : Google Scholar : PubMed/NCBI
22	Thio CL, Mosbruger TL, Kaslow RA, Karp CL, Strathdee SA, Vlahov D, O'Brien SJ, Astemborski J and Thomas DL: Cytotoxic T-lymphocyte antigen 4 gene and recovery from hepatitis B virus infection. J Virol. 78:11258–11262. 2004. View Article : Google Scholar : PubMed/NCBI