A critical role of T follicular helper cells in human mucosal anti-influenza response that can be enhanced by immunological adjuvant CpG-DNA

作者：Aljurayyan A N; Sharma R; Upile N; Beer H; Vaughan C; Xie C; Achar P; Ahmed M S; McNamara P S; Gordon S B; Zhang Q

来源：Antiviral Research, 2016, 132: 122-130.

DOI：10.1016/j.antivira1.2016.05.021

• T follicular helper cell (T-FH)
• Influenza virus
• Influenza vaccine
• Anti-hemagglutinin (HA) antibody response
• Nasopharynx-associated lymphoid tissues (NALT)
• CpG-DNA
• Children and adults

T Follicular helper cells (T-FH) are considered critical for B cell antibody response, and recent efforts have focused on promoting T-FH in order to enhance vaccine efficacy. We studied the frequency and function of T-FH in nasopharynx-associated lymphoid tissues (NALT) from children and adults, and its role in anti influenza antibody response following stimulation by a live-attenuated influenza vaccine (LAIV) or an inactivated seasonal virus antigen (sH1N1). We further studied whether CpG-DNA promotes T-FH and by which enhances anti-influenza response. We showed NALT from children aged 1.5-10 years contained abundant T-FH, suggesting efficient priming of T-FH during early childhood. Stimulation by LAIV induced a marked increase in T-FH that correlated with a strong production of anti-hemagglutinin (HA) IgAilgG/IgM antibodies in tonsillar cells. Stimulation by the inactivated sH1N1 antigen induced a small increase in T-FH which was markedly enhanced by CpG-DNA, accompanied by enhanced anti-HA antibody responses. In B cell co-culture experiment, anti-HA responses were only seen in the presence of T-FH, and addition of plasmacytoid dendritic cell to T-FH-B cell co-culture enhanced the T-FH-mediated antibody production following CpG-DNA and 5H1N1 antigen stimulation. Induction of TFH differentiation from nave T cells was also shown following the stimulation. Our results support a critical role of T-FH in human mucosal anti-influenza antibody response. Use of an adjuvant such as CpG-DNA that has the capacity to promote T-FH by which to enhance antigen-induced antibody responses in NALT tissue may have important implications for future vaccination strategies against respiratory pathogens.

• 出版日期2016-8