Increased frequency of circulating follicular helper T cells in children with hand, foot, and mouth disease caused by enterovirus 71 infection

J Immunol Res. 2014;2014:651872. doi: 10.1155/2014/651872. Epub 2014 Jun 11.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology
  • Antigens, Surface / metabolism
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cytokines / blood
  • Cytokines / genetics
  • Cytokines / metabolism
  • Enterovirus A, Human / immunology*
  • Female
  • Flow Cytometry
  • Gene Expression
  • Hand, Foot and Mouth Disease / blood
  • Hand, Foot and Mouth Disease / diagnosis
  • Hand, Foot and Mouth Disease / immunology*
  • Humans
  • Immunophenotyping
  • Infant
  • Lymphocyte Count
  • Male
  • Receptors, CXCR5 / metabolism
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism


  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Surface
  • Cytokines
  • Receptors, CXCR5