tetano
Editor, Senior Moderator
J Virol. 2014 Jun 4. pii: JVI.00534-14. [Epub ahead of print]
Crucial role of IL-7 in the development of T follicular helper cells as well as the induction of humoral immunity.
Seo YB1, Im SJ1, Namkoong H1, Kim SW1, Choi YW2, Kang MC2, Lim HS3, Jin HT3, Yang SH3, Cho ML4, Kim YM5, Lee SW5, Choi YK6, Surh CD5, Sung YC7.
Author information
Abstract
T follicular helper (Tfh) cells are specialized providers of cognate B cell help which is important in promoting the induction of high affinity antibody production in germinal centers (GCs). IL-6 and IL-21 have been known to play important roles in Tfh cell differentiation. Here, we demonstrate that IL-7 plays a pivotal role in Tfh generation and GC formation in vivo, as treatment with anti-IL-7 neutralizing antibody markedly impaired the development of Tfh cells and IgG responses. Moreover, codelivery of mouse Fc-fused IL-7 (IL-7-mFc) with a vaccine enhanced the generation of GC B cells as well as Tfh cells, but not other lineages of T helper cells, including Th1, Th2, and Th17 cells. Interestingly, a six-fold-lower dose of an influenza vaccine codelivered with Fc-fused IL-7 induced higher antigen-specific and cross-reactive IgG titers than the vaccine alone in both mice and monkeys, and led to markedly enhanced protection against heterologous influenza virus challenge in mice. Enhanced generation of Tfh cells by IL-7-mFc treatment was not significantly affected by the neutralization of IL-6 and IL-21, indicating an independent role of IL-7 on Tfh differentiation. Thus, IL-7 holds promise as a critical cytokine for selectively inducing Tfh cell generation and enhancing protective IgG responses.
IMPORTANCE:
Here, we demonstrate for the first time that co-delivery of Fc-fused IL-7 significantly increased influenza vaccine-induced antibody responses, accompanied by robust expansion of Tfh cells and GC B cells as well as enhanced GC formation. Furthermore, IL-7-mFc induced earlier and cross-reactive IgG responses, leading to striking protection against heterologous influenza challenge. These results suggest that Fc-fused IL-7 could be used for inducing strong and cross-protective humoral immunity against highly mutable viruses such as HIV and hepatitis C virus, as well as influenza viruses.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
24899182
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24899182
Crucial role of IL-7 in the development of T follicular helper cells as well as the induction of humoral immunity.
Seo YB1, Im SJ1, Namkoong H1, Kim SW1, Choi YW2, Kang MC2, Lim HS3, Jin HT3, Yang SH3, Cho ML4, Kim YM5, Lee SW5, Choi YK6, Surh CD5, Sung YC7.
Author information
Abstract
T follicular helper (Tfh) cells are specialized providers of cognate B cell help which is important in promoting the induction of high affinity antibody production in germinal centers (GCs). IL-6 and IL-21 have been known to play important roles in Tfh cell differentiation. Here, we demonstrate that IL-7 plays a pivotal role in Tfh generation and GC formation in vivo, as treatment with anti-IL-7 neutralizing antibody markedly impaired the development of Tfh cells and IgG responses. Moreover, codelivery of mouse Fc-fused IL-7 (IL-7-mFc) with a vaccine enhanced the generation of GC B cells as well as Tfh cells, but not other lineages of T helper cells, including Th1, Th2, and Th17 cells. Interestingly, a six-fold-lower dose of an influenza vaccine codelivered with Fc-fused IL-7 induced higher antigen-specific and cross-reactive IgG titers than the vaccine alone in both mice and monkeys, and led to markedly enhanced protection against heterologous influenza virus challenge in mice. Enhanced generation of Tfh cells by IL-7-mFc treatment was not significantly affected by the neutralization of IL-6 and IL-21, indicating an independent role of IL-7 on Tfh differentiation. Thus, IL-7 holds promise as a critical cytokine for selectively inducing Tfh cell generation and enhancing protective IgG responses.
IMPORTANCE:
Here, we demonstrate for the first time that co-delivery of Fc-fused IL-7 significantly increased influenza vaccine-induced antibody responses, accompanied by robust expansion of Tfh cells and GC B cells as well as enhanced GC formation. Furthermore, IL-7-mFc induced earlier and cross-reactive IgG responses, leading to striking protection against heterologous influenza challenge. These results suggest that Fc-fused IL-7 could be used for inducing strong and cross-protective humoral immunity against highly mutable viruses such as HIV and hepatitis C virus, as well as influenza viruses.
Copyright ? 2014, American Society for Microbiology. All Rights Reserved.
PMID:
24899182
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24899182