T follicular helper 17 (Tfh17) cells are superior for immunological memory maintenance

  1. Xin Gao
  2. Kaiming Luo
  3. Diya Wang
  4. Yunbo Wei
  5. Yin Yao
  6. Jun Deng
  7. Yang Yang
  8. Qunxiong Zeng
  9. Xiaoru Dong
  10. Le Xiong
  11. Dongcheng Gong
  12. Lin Lin
  13. Kai Pohl
  14. Shaoling Liu
  15. Yu Liu
  16. Lu Liu
  17. Thi HO Nguyen
  18. Lilith F Allen
  19. Katherine Kedzierska
  20. Yanliang Jin
  21. Mei-Rong Du
  22. Wanping Chen
  23. Liangjing Lu
  24. Nan Shen
  25. Zheng Liu
  26. Ian A Cockburn  Is a corresponding author
  27. Wenjing Luo  Is a corresponding author
  28. Di Yu  Is a corresponding author
  1. Australian National University, Australia
  2. Shanghai Jiao Tong University, China
  3. Fourth Military Medical University, China
  4. Qilu University of Technology, China
  5. University of Queensland, Australia
  6. Obstetrics and Gynecology Hospital of Fudan University, China
  7. University of Melbourne, Australia

Abstract

A defining feature of successful vaccination is the ability to induce long-lived antigen-specific memory cells. T follicular helper (Tfh) cells specialize in providing help to B cells in mounting protective humoral immunity in infection and after vaccination. Memory Tfh cells that retain the CXCR5 expression can confer protection through enhancing humoral response upon antigen re-exposure but how they are maintained is poorly understood. CXCR5+ memory Tfh cells in human blood are divided into Tfh1, Tfh2 and Tfh17 cells by the expression of chemokine receptors CXCR3 and CCR6 associated with Th1 and Th17 respectively. Here, we developed a new method to induce Tfh1, Tfh2 and Tfh17-like (iTfh1, iTfh2 and iTfh17) mouse cells in vitro. Although all three iTfh subsets efficiently support antibody responses in recipient mice with immediate immunization, iTfh17 cells are superior to iTfh1 and iTfh2 cells in supporting antibody response to a later immunization after extended resting in vivo to mimic memory maintenance. Notably, the counterpart human Tfh17 cells are selectively enriched in CCR7+ central memory Tfh cells with survival and proliferative advantages. Furthermore, the analysis of multiple human cohorts that received different vaccines for HBV, influenza virus, tetanus toxin or measles revealed that vaccine-specific Tfh17 cells outcompete Tfh1 or Tfh2 cells for the persistence in memory phase. Therefore, the complementary mouse and human results showing the advantage of Tfh17 cells in maintenance and memory function supports the notion that Tfh17-induced immunization might be preferable in vaccine development to confer long-term protection.

Data availability

Sequencing data have been deposited in GEO under the accession code GSE167309.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Xin Gao

    Immunology and Infectious Disease Division, Australian National University, Cabnerra, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5927-2241
  2. Kaiming Luo

    China-Australia Centre for Personalised Immunology, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Diya Wang

    Department of Occupational and Environmental Health, Fourth Military Medical University, Xi'an, China
    Competing interests
    The authors declare that no competing interests exist.
  4. Yunbo Wei

    Laboratory of Immunology for Environment and Health, Qilu University of Technology, Jinan, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Yin Yao

    Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University, Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Jun Deng

    China-Australia Centre for Personalised Immunology, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Yang Yang

    Faculty of Medicine, University of Queensland, Brisbane, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Qunxiong Zeng

    China-Australia Centre for Personalised Immunology, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Xiaoru Dong

    Department of Occupational and Environmental Health, Fourth Military Medical University, Xi'an, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Le Xiong

    Department of Rheumatology, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Dongcheng Gong

    China-Australia Centre for Personalised Immunology, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  12. Lin Lin

    Department of Laboratory Medicine, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Kai Pohl

    Immunology and Infectious Disease Division, Australian National University, Cabnerra, Australia
    Competing interests
    The authors declare that no competing interests exist.
  14. Shaoling Liu

    Shanghai Children's Medical Centre, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  15. Yu Liu

    Shanghai Children's Medical Centre, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  16. Lu Liu

    Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  17. Thi HO Nguyen

    Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  18. Lilith F Allen

    Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
  19. Katherine Kedzierska

    Department of Microbiology and Immunology, University of Melbourne, Melbourne, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6141-335X
  20. Yanliang Jin

    Shanghai Children's Medical Centre, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  21. Mei-Rong Du

    Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  22. Wanping Chen

    Department of Occupational and Environmental Health, Fourth Military Medical University, Xi'an, China
    Competing interests
    The authors declare that no competing interests exist.
  23. Liangjing Lu

    Department of Rheumatology, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  24. Nan Shen

    China-Australia Centre for Personalised Immunology, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  25. Zheng Liu

    Department of Otolaryngology-Head and Neck Surgery, Shanghai Jiao Tong University, Shanghai, China
    Competing interests
    The authors declare that no competing interests exist.
  26. Ian A Cockburn

    Immunology and Infectious Disease Division, Australian National University, Cabnerra, Australia
    For correspondence
    ian.cockburn@anu.edu.au
    Competing interests
    The authors declare that no competing interests exist.
  27. Wenjing Luo

    Department of Occupational and Environmental Health, Fourth Military Medical University, Xi'an, China
    For correspondence
    luowenj@fmmu.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
  28. Di Yu

    Frazer Institute, Faculty of Medicine, University of Queensland, Brisbane, Australia
    For correspondence
    di.yu@uq.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1721-8922

Funding

National Health and Medical Research Council (GNT2009554,GNT200046,GNT1194036,GNT1158404,6)

  • Thi HO Nguyen
  • Katherine Kedzierska
  • Ian A Cockburn
  • Di Yu

National Natural Science Foundation of China (82130030,81920108011,82101198)

  • Yin Yao
  • Zheng Liu

National Key Research and Development Program of China (2017YFC0909003)

  • Liangjing Lu

Natural Science Foundation of Shandong Province (ZR2020ZD41,2021ZDSYS12)

  • Yunbo Wei

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Tomohiro Kurosaki, Osaka University, Japan

Ethics

Animal experimentation: All animal experiments were carried under protocols (ethics number: A2019/36) approved byANU's animal ethics committee.

Human subjects: Written informed consent was obtained from participants or the parents of children participants according to the ethics approved by human ethics committees of Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine (KY2019-161), Fourth Military Medical University (KY20163344-1), Tongji Hospital (NCT05009134), Shanghai Children's Medical Centre affiliated to Shanghai Jiao Tong University School of Medicine and Obstetrics and Gynecology Hospital of Fudan University (Kyy2018-6).

Version history

  1. Received: July 27, 2022
  2. Preprint posted: July 31, 2022 (view preprint)
  3. Accepted: January 18, 2023
  4. Accepted Manuscript published: January 19, 2023 (version 1)
  5. Version of Record published: February 1, 2023 (version 2)

Copyright

© 2023, Gao et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Xin Gao
  2. Kaiming Luo
  3. Diya Wang
  4. Yunbo Wei
  5. Yin Yao
  6. Jun Deng
  7. Yang Yang
  8. Qunxiong Zeng
  9. Xiaoru Dong
  10. Le Xiong
  11. Dongcheng Gong
  12. Lin Lin
  13. Kai Pohl
  14. Shaoling Liu
  15. Yu Liu
  16. Lu Liu
  17. Thi HO Nguyen
  18. Lilith F Allen
  19. Katherine Kedzierska
  20. Yanliang Jin
  21. Mei-Rong Du
  22. Wanping Chen
  23. Liangjing Lu
  24. Nan Shen
  25. Zheng Liu
  26. Ian A Cockburn
  27. Wenjing Luo
  28. Di Yu
(2023)
T follicular helper 17 (Tfh17) cells are superior for immunological memory maintenance
eLife 12:e82217.
https://doi.org/10.7554/eLife.82217

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https://doi.org/10.7554/eLife.82217

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