Immunology and Infectious Disease Division, John Curtin School of Medical Research, The Australian National University, Canberra, Australia; China-Australia Centre for Personalised Immunology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Kaiming Luo
China-Australia Centre for Personalised Immunology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Diya Wang
Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, China
Yunbo Wei
Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology, Shandong Academy of Sciences, Jinan, China
Yin Yao
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Jun Deng
China-Australia Centre for Personalised Immunology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Yang Yang
Frazer Institute, Faculty of Medicine, University of Queensland, Brisbane, Australia
Qunxiong Zeng
China-Australia Centre for Personalised Immunology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Xiaoru Dong
Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, China
Le Xiong
Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Dongcheng Gong
China-Australia Centre for Personalised Immunology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Lin Lin
Department of Laboratory Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Kai Pohl
Immunology and Infectious Disease Division, John Curtin School of Medical Research, The Australian National University, Canberra, Australia
Shaoling Liu
Shanghai Children's Medical Centre, Shanghai Jiao Tong University, Shanghai, China
Yu Liu
Shanghai Children's Medical Centre, Shanghai Jiao Tong University, Shanghai, China
Lu Liu
Obstetrics and Gynecology Hospital of Fudan University (Shanghai Red House Obstetrics and Gynecology Hospital), Shanghai, China
Thi HO Nguyen
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia
Lilith F Allen
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia
Yanliang Jin
Shanghai Children's Medical Centre, Shanghai Jiao Tong University, Shanghai, China
Mei-Rong Du
Obstetrics and Gynecology Hospital of Fudan University (Shanghai Red House Obstetrics and Gynecology Hospital), Shanghai, China
Wanping Chen
Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, China
Liangjing Lu
Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Nan Shen
China-Australia Centre for Personalised Immunology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Zheng Liu
Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Ian A Cockburn
Immunology and Infectious Disease Division, John Curtin School of Medical Research, The Australian National University, Canberra, Australia
Wenjing Luo
Department of Occupational and Environmental Health and the Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, China
Immunology and Infectious Disease Division, John Curtin School of Medical Research, The Australian National University, Canberra, Australia; Frazer Institute, Faculty of Medicine, University of Queensland, Brisbane, Australia; Ian Frazer Centre for Children’s Immunotherapy Research, Children’s Health Research Centre, Faculty of Medicine, University of Queensland, Brisbane, Australia
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.
