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Follicular helper T cell and memory B cell immunity in CHC patients

  • Yong Liu
  • Huifan Ji
  • Pingwei Zhao
  • Hongqing Yan
  • Yanjun Cai
  • Lei Yu
  • Xiaoli Hu
  • Xiguang Sun
  • Yanfang JiangEmail author
Original Article
  • 89 Downloads

Abstract

Chronic hepatitis C (CHC) is associated with biological activity of T follicular helper (Tfh) cells and memory B cells (MBCs). However, the nature of Tfh cell subsets that are responsible for MBCs in CHC patients has not been evaluated. This study aimed to investigate Tfh and MBC immunity before and after direct-acting antiviral (DAA) therapy in patients with CHC. A total of 31 CHC patients and 15 healthy controls (HCs) were recruited. Individual patients were treated with sofosbuvir/ribavirin (SOF/RBV) or in combination with pegylated interferon alpha-2a (PEG-IFN-α-2a) for 12 weeks. Immunofluorescence revealed the frequency of ICOS+CD4+CXCR5+ active Tfh cells in liver tissue of CHC patients was higher than that of healthy control. Tfh and B cell co-culture experiments showed that Tfh2 cells from CHC patients have potential ability to induce B cell differentiation and IgG production. Flow cytometry showed that the frequencies of CD21CD27+IgD activated MBCs, ICOS+CD4+CXCR5+ activated Tfh cells, Tfh1 (IFN-γ+CD4+CXCR5+) cells, and Tfh2 (IL-4+CD4+CXCR5+) cells, but not of Tfh17 (IL-17+CD4+CXCR5+) cells, increased in CHC patients before and after DAA therapy. Collectively, ICOS+ Tfh, Tfh1, Tfh2 cells, and MBCs participated in the antiviral treatment process of SOF/RBV with or without PEG-IFN-α-2a in CHC patients, and their activity was further enhanced during the treatment.

Key messages

  • This study aimed to investigate Tfh cells and MBC immunity in CHC patients.

  • CD21CD27+IgD activated MBCs increased in CHC patients before and after treatment.

  • Tfh1 and Tfh2 cells increased in CHC patients before and after antiviral treatment.

  • Intrahepatic activated Tfh cells increased in CHC patients before treatment.

  • Tfh2 cells from CHC patients have a stronger ability to induce B cell differentiation.

Keywords

Chronic hepatitis C T follicular helper cell Memory B cell Antiviral treatment Immune response 

Notes

Acknowledgments

The authors sincerely thank Ms. Yingbo Li and Ms. Rongjing Dang for their technical assistance.

Funding information

This work was supported by the National Natural Science Foundation of China (Nos. 30972610, 81273240, 91742107, and 81570002), Jilin Province Science and Technology Agency (Nos. 20190101022JH, 20160101037JC, 20170622009JC, 2017C021, 2017J039, SXGJXX2017-8), Norman Bethune Program of Jilin University (2012206), and The fund of the State Key Laboratory of Kidney Diseases in PLA General Hospital.

Compliance with ethical standards

Ethical standards

Written informed consent was obtained from each participant. The experimental protocol was established according to the guidelines of the Declaration of Helsinki and was approved by the Human Ethics Committee of the First Hospital of Jilin University (No. 2014-301, Jilin University, Changchun, China).

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

109_2018_1735_MOESM1_ESM.pdf (242 kb)
ESM 1 (PDF 242 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Yong Liu
    • 1
  • Huifan Ji
    • 2
  • Pingwei Zhao
    • 1
  • Hongqing Yan
    • 2
  • Yanjun Cai
    • 2
  • Lei Yu
    • 3
  • Xiaoli Hu
    • 4
  • Xiguang Sun
    • 1
  • Yanfang Jiang
    • 1
    • 5
    Email author
  1. 1.Genetic Diagnosis CenterThe First Hospital of Jilin UniversityChangchunChina
  2. 2.Department of HepatologyThe First Hospital of Jilin UniversityChangchunChina
  3. 3.Department of Infectious DiseaseThe Fourth Hospital of Harbin Medical UniversityHarbinChina
  4. 4.Department of Infectious DiseaseHeilongjiang Provincial HospitalHarbinChina
  5. 5.Key Laboratory of Zoonosis Research, Ministry of EducationThe First Hospital of Jilin UniversityChangchunChina

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