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.
Sequencing data have been deposited in GEO under the accession code GSE167309.
T Follicular Helper 17 (Tfh17) Cells are Superior for Immunological Memory MaintenanceNCBI Gene Expression Omnibus, GSE167309.
Imbalance of regulatory and cytotoxic SARS-CoV-2-reactive CD4+ T cells in COVID-19NCBI Gene Expression Omnibus, GSE152522.
Clonal replacement of tumor-specific T cells following PD-1 blockade [bulk RNA]NCBI Gene Expression Omnibus, GSE123812.
- Thi HO Nguyen
- Katherine Kedzierska
- Ian A Cockburn
- Di Yu
- Yin Yao
- Zheng Liu
- Liangjing Lu
- Yunbo Wei
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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).
- Tomohiro Kurosaki, Osaka University, Japan
© 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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