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

Wang,Dongsheng; Zhou,Ding'an; Du,Qin; Liang,Qi; Wang,Qiang; Fang,Li; Wang,Guangrong; Fan,Quming; Liu,Beizhong; Zhou,Jingguo; Tang,Zhong; Wu,Hao; Guo,Xiaolan; Jiao,Yanmei; Zhang,Guoyuan

doi:10.3892/mmr.2013.1326

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

Authors:
- Dongsheng Wang
- Ding'an Zhou
- Qin Du
- Qi Liang
- Qiang Wang
- Li Fang
- Guangrong Wang
- Quming Fan
- Beizhong Liu
- Jingguo Zhou
- Zhong Tang
- Hao Wu
- Xiaolan Guo
- Yanmei Jiao
- Guoyuan Zhang
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Affiliations: Department of Laboratory Medicine, The Affiliated Hospital of North Sichuan Medical College, Sichuan 637000, P.R. China, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, P.R. China, Medical Laboratory Center of Yongchuan Hospital, Chongqing Medical University, Chongqing 402160, P.R. China, Center for Infectious Diseases, Beijing You'an Hospital, Capital Medical University, Beijng 100069, P.R. China
Published online on: February 19, 2013 https://doi.org/10.3892/mmr.2013.1326
Pages: 1197-1202

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Abstract

Previous studies have indicated that immune dysregulation is an important cause of HCV‑mediated damage to the liver. Co‑stimulation signals, including programmed cell death protein 1 (PD‑1) and inducible T‑cell co‑stimulator (ICOS), have been demonstrated to be involved in the pathogenesis of HCV. The purpose of this study was to investigate the soluble PD‑1 (sPD‑1) and soluble ICOS (sICOS) serum levels in chronic HCV patients, and to elucidate the association of sPD‑1 and sICOS levels with pathological injury of chronic HCV infection. Sixty‑three patients with chronic HCV and 30 normal controls were recruited for this study. The serum concentration levels of sPD‑1 and sICOS were measured by enzyme‑linked immunosorbent assay, and the mRNA levels of PD‑1 and ICOS were detected using real‑time RT‑PCR. The serum sPD‑1 and sICOS levels were significantly elevated in the chronic HCV patient group compared with the normal control group. Furthermore, the relative mRNA expression levels of these proteins were also increased in chronic HCV patients. sPD‑1 and sICOS serum levels were significantly correlated with anti‑HCV antibody levels, but not with HCV RNA. Aberrant sPD‑1 and sICOS serum levels may reflect the dysregulation of T‑cell activation, and are associated with the pathological injury of chronic HCV infection.

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1	Sorrell MF, Belongia EA, Costa J, Gareen IF, Grem JL, Inadomi JM, Kern ER, McHugh JA, Petersen GM, Rein MF, et al: National Institutes of Health consensus development conference statement: management of hepatitis B. Hepatology. 49:S4–S12. 2009. View Article : Google Scholar : PubMed/NCBI
2	Rodriguez-Luna H and Vargas HE: Management of hepatitis C virus infection in the setting of liver transplantation. Liver Transpl. 11:479–489. 2005. View Article : Google Scholar : PubMed/NCBI
3	Mengshol JA, Golden-Mason L and Rosen HR: Mechanisms of Disease: HCV-induced liver injury. Nat Clin Pract Gastroenterol Hepatol. 4:622–634. 2007. View Article : Google Scholar : PubMed/NCBI
4	Sharpe AH and Freeman GJ: The B7-CD28 superfamily. Nat Rev Immunol. 2:116–126. 2002. View Article : Google Scholar
5	Cooper S, Erickson AL, Adams EJ, Kansopon J, Weiner AJ, Chien DY, Houghton M, Parham P and Walker CM: Analysis of a successful immune response against hepatitis C virus. Immunity. 10:439–449. 1999. View Article : Google Scholar : PubMed/NCBI
6	Thimme R, Oldach D, Chang KM, Steiger C, Ray SC and Chisari FV: Determinants of viral clearance and persistence during acute hepatitis C virus infection. J Exp Med. 194:1395–1406. 2001. View Article : Google Scholar : PubMed/NCBI
7	Puig M, Mihalik K, Tilton JC, Williams O, Merchlinsky M, Connors M, Feinstone SM and Major ME: CD4⁺ immune escape and subsequent T-cell failure following chimpanzee immunization against hepatitis C virus. Hepatology. 44:736–745. 2006.
8	Rehermann B, Chang KM, McHutchinson J, Kokka R, Houghton M, Rice CM and Chisari FV: Differential cytotoxic T-lymphocyte responsiveness to the hepatitis B and C viruses in chronically infected patients. J Virol. 70:7092–7102. 1996.PubMed/NCBI
9	Nelson DR, Marousis CG, Davis GL, Rice CM, Wong J, Houghton M and Lau JY: The role of hepatitis C virus-specific cytotoxic T lymphocytes in chronic hepatitis C. J Immunol. 158:1473–1481. 1997.PubMed/NCBI
10	Cabrera R, Tu Z, Xu Y, Firpi RJ, Rosen HR, Liu C and Nelson DR: An immunomodulatory role for CD4(+)CD25(+) regulatory T lymphocytes in hepatitis C virus infection. Hepatology. 40:1062–1071. 2004.
11	Yao ZQ, King E, Prayther D, Yin D and Moorman J: T cell dysfunction by hepatitis C virus core protein involves PD-1/PDL-1 signaling. Viral Immunol. 20:276–287. 2007. View Article : Google Scholar : PubMed/NCBI
12	Li S, Roberts S, Plebanski M, Gouillou M, Spelman T, Latour P, Jackson D, Brown L, Sparrow RL, Prince HM, et al: Induction of multi-functional T cells in a phase I clinical trial of dendritic cell immunotherapy in hepatitis C virus infected individuals. PLoS One. 7:e393682012. View Article : Google Scholar : PubMed/NCBI
13	Kasprowicz V, Schulze Zur Wiesch J, Kuntzen T, Nolan BE, Longworth S, Berical A, Blum J, McMahon C, Reyor LL, Elias N, et al: High level of PD-1 expression on hepatitis C virus (HCV)-specific CD8⁺ and CD4⁺ T cells during acute HCV infection, irrespective of clinical outcome. J Virol. 82:3154–3160. 2008. View Article : Google Scholar : PubMed/NCBI
14	Rutebemberwa A, Ray SC, Astemborski J, Levine J, Liu L, Dowd KA, Clute S, Wang C, Korman A, Sette A, et al: High-programmed death-1 levels on hepatitis C virus-specific T cells during acute infection are associated with viral persistence and require preservation of cognate antigen during chronic infection. J Immunol. 181:8215–8225. 2008. View Article : Google Scholar
15	Atsukawa M, Nakatsuka K, Kobayashi T, Shimizu M, Tamura H, Harimoto H, Takahashi H and Sakamoto C: Ribavirin downmodulates inducible costimulator on CD4⁺ T cells and their interleukin-10 secretion to assist in hepatitis C virus clearance. J Gastroenterol Hepatol. 27:823–831. 2012.PubMed/NCBI
16	Nielsen C, Ohm-Laursen L, Barington T, Husby S and Lillevang ST: Alternative splice variants of the human PD-1 gene. Cell Immunol. 235:109–116. 2005. View Article : Google Scholar : PubMed/NCBI
17	Meng Q, Yang P, Li B, Zhou H, Huang X, Zhu L, Ren Y and Kijlstra A: CD4⁺PD-1⁺ T cells acting as regulatory cells during the induction of anterior chamber-associated immune deviation. Invest Ophthalmol Vis Sci. 47:4444–4452. 2006.PubMed/NCBI
18	Klenerman P and Semmo N: Cellular immune responses against persistent hepatitis C virus: gone but not forgotten. Gut. 55:914–916. 2006. View Article : Google Scholar : PubMed/NCBI
19	Koziel MJ: Cellular immune responses against hepatitis C virus. Clin Infect Dis. 41(Suppl 1): S25–S31. 2005. View Article : Google Scholar : PubMed/NCBI
20	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
21	Nishimura H, Nose M, Hiai H, Minato N and Honjo T: Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity. 11:141–151. 1999. View Article : Google Scholar : PubMed/NCBI
22	Greenwald RJ, Freeman GJ and Sharpe AH: The B7 family revisited. Annu Rev Immunol. 23:515–548. 2005. View Article : Google Scholar : PubMed/NCBI
23	Witsch EJ, Peiser M, Hutloff A, Buchner K, Dorner BG, Jonuleit H, Mages HW and Kroczek RA: ICOS and CD28 reversely regulate IL-10 on re-activation of human effector T cells with mature dendritic cells. Eur J Immunol. 32:2680–2686. 2002. View Article : Google Scholar : PubMed/NCBI
24	Warnatz K, Bossaller L, Salzer U, Skrabl-Baumgartner A, Schwinger W, van der Burg M, van Dongen JJ, Orlowska-Volk M, Knoth R, Durandy A, et al: Human ICOS deficiency abrogates the germinal center reaction and provides a monogenic model for common variable immunodeficiency. Blood. 107:3045–3052. 2006. View Article : Google Scholar : PubMed/NCBI
25	Nakamoto N, Cho H, Shaked A, Olthoff K, Valiga ME, Kaminski M, Gostick E, Price DA, Freeman GJ, Wherry EJ and Chang KM: Synergistic reversal of intrahepatic HCV-specific CD8 T cell exhaustion by combined PD-1/CTLA-4 blockade. PLoS Pathog. 5:e10003132009. View Article : Google Scholar : PubMed/NCBI