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Tfh17 Cells Have Superior Memory Maintenance in Vaccination

Xin Gao,1,2 Kaiming Luo,2 Yunbo Wei,3 Qunxiong Zeng,4 Le Xiong,4 Dongcheng Gong,2 Lin Lin,5 Kai Pohl,1 Ian A. Cockburn,1 Di Yu 2,6

1 Department of Immunology and Infectious Disease, John Curtin School of Medical Research, The Australian National University 2 China-Australia Centre for Personalised Immunology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University 3 Laboratory of Immunology for Environment and Health, Shandong Analysis and Test Center, Qilu University of Technology, Shandong Academy of Sciences 4 Department of Rheumatology, Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University 5 Department of Laboratory Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University 6 Diamantina Institute, Faculty of Medicine, The University of Queensland

A defining feature of successful vaccine is the ability to induce long-lived antigen specific memory cells. Circulating memory follicular helper T (cTfh) cells, defined as CXCR5+CD4+ T cells in the blood, can confer protection through quickly supporting early humoral response upon antigen reexposure. cTfh cells have been divided into Tfh1, Tfh17 and Tfh2 cells by CXCR3 and CCR6, however, their memory maintenance remains uninvestigated. In this study, we investigated the memory maintenance of Tfh1, Tfh17 and Tfh2 cells in both human and mouse vaccination studies. We found human Tfh17 cells comparing with Tfh1 or Tfh2 cells, were phenotypically more central-memory (CM), preferentially survived into memory phase upon vaccination, and dominated vaccine specific long-lived cTfh cells. Mouse studies showed Tfh17-polarized cells had better Tfh memory and induced stronger antibody response after resting and re-immunization. Our study for the first time revealed the differential contribution of Tfh1, Tfh17 and Tfh2 cells to the maintenance of humoral immunological memory. Notably, our research suggested that Tfh17-polarized immunization was preferable in future vaccine development to confer long-term protection.