title: Increased frequency of circulating follicular helper T cells in children with hand, foot, and mouth disease caused by enterovirus 71 infection.
abstract: Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD) in children. The role of T follicular helper (TFH) cells in EV71-infected children remains unclear in regulating humoral immunity. The frequency of circulating ICOS(high)/PD-1(high)CXCR5(+)CD4(+) TFH cells in the children with mild and severe EV71 infection and healthy controls (HC) was detected by flow cytometry, respectively. IL-21 and IL-6 mRNA expression and their serum levels, Bcl-6 mRNA expression, and specific neutralizing antibodies against EV71 (NAb-EV71) were measured. In the acute stage of patients with EV71 infection, increased frequencies of circulating TFH cells with ICOS(high) and PD-1(high) expression in the mild and severe patients were observed, and the positive correlations among the frequencies of circulating TFH cells and the serum levels of IL-21, IL-6, and NAb-EV71 titres were detected, respectively. Moreover, the expressions of IL-6 and IL-21 mRNA in PBMCs from patients were also significantly higher than those of HC. However, further analysis did not reveal any significant differences between mild and severe patients. These data indicate a role of TFH cells and associated cytokines in modulating the humoral response during the pathogenesis of EV71 infection.
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: David
authors.initials: D
authors.lastname: Cui
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: Xianzhi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: Jianzhou
authors.initials: J
authors.lastname: Lou
authors.affiliation: Department of Clinical Laboratory, Center of Community Health Service of Qingbo Street, Hangzhou 310002, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: Xianfei
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: Zhimei
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: Dejian
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Huo
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Xie
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: Shufa
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.affiliation: Department of Pathology and Center of Infection and Immunology, The University of Hong Kong, Hong Kong.
authors.forename: Liwei
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Clinical Laboratory, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000367:Age Factors; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D000954:Antigens, Surface / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000378:metabolism; D029821:Enterovirus A, Human / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D006232:Hand, Foot and Mouth Disease / Q000097:blood / Q000175:diagnosis / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D018655:Lymphocyte Count; D008297:Male; D054380:Receptors, CXCR5 / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000954:Antigens, Surface; D016207:Cytokines; D054380:Receptors, CXCR5