tetano
Editor, Senior Moderator
J Virol. 2018 Mar 21. pii: JVI.00114-18. doi: 10.1128/JVI.00114-18. [Epub ahead of print]
[h=1]Activation and induction of antigen-specific T follicular helper cells (TFH) play a critical role in LAIV-induced human mucosal anti-influenza antibody response.[/h] Aljurayyan A[SUP]1[/SUP], Puksuriwong S[SUP]1[/SUP], Ahmed M[SUP]1[/SUP], Sharma R[SUP]2[/SUP], Krishnan M[SUP]2[/SUP], Sood S[SUP]2[/SUP], Davies K[SUP]3[/SUP], Rajashekar D[SUP]3[/SUP], Leong S[SUP]4[/SUP], McNamara PS[SUP]5[/SUP], Gordon S[SUP]6[/SUP], Zhang Q[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] There is increasing interest recently in developing intranasal vaccines against respiratory tract infections. Antibody response is critical in vaccine-induced protection and T[SUB]FH[/SUB] is considered important in mediating antibody response. Most data supporting the role for T[SUB]FH[/SUB] in antibody response are from animal studies, and direct evidence from humans is limited, apart from T[SUB]FH[/SUB]-like cells in blood. We studied activation and induction of T[SUB]FH[/SUB] and its role on anti-influenza antibody response by live-attenuated influenza vaccine(LAIV) in human nasopharynx-associated lymphoid tissue(NALT). T[SUB]FH[/SUB] activation in adenotonsillar tissues were analysed by flow-cytometry, and anti-hemagglutinin(HA) antibodies examined following LAIV stimulation of tonsillar mononuclear cells(MNC). Induction of antigen-specific T[SUB]FH[/SUB] by LAIV was studied by flow-cytometry for induced T[SUB]FH[/SUB] and CD154 expression. LAIV induced T[SUB]FH[/SUB] proliferation which correlated with anti-HA antibody production, and T[SUB]FH[/SUB] was shown critical for antibody response. Induction of T[SUB]FH[/SUB] from na?ve T cells by LAIV was shown in newly induced T[SUB]FH[/SUB] expressing BCL6 and CD21, which was followed by the detection of anti-HA antibodies. Antigen specificity of LAIV-induced T[SUB]FH[/SUB] was demonstrated by the expression of antigen-specific T cell activation marker CD154 upon challenge by H1N1 virus antigen or HA. LAIV-induced T[SUB]FH[/SUB] differentiation was inhibited by BCL6, IL21, ICOS and CD40 signalling blocking respectively, and that diminished anti-HA antibody production.
[h=4]CONCLUSION:[/h] We demonstrate for the first time the induction of antigen-specific T[SUB]FH[/SUB] by LAIV in human NALT that provide critical support for anti-influenza antibody response. Promoting antigen-specific T[SUB]FH[/SUB] in NALT by intranasal vaccines may provide an effective vaccination strategy against respiratory infections in humans.IMPORTANCE. Airway infection such as influenza is common in humans. Intranasal vaccination has been considered a more biologically relevant and effective way of immunization against airway infection. Vaccine-induced antibody response is crucial for protection against infection. Recent data from animal studies suggest one type of T cells, named T[SUB]FH[/SUB] is important for the antibody response. However, data on whether this T[SUB]FH[/SUB]-mediated help for antibody production operates in humans is limited, due to the lack of access to human immune tissue containing the T[SUB]FH[/SUB] In this study, we demonstrated the induction of T[SUB]FH[/SUB] cells by an intranasal influenza vaccine in human immune tissue that provide critical support for anti-influenza antibody response. Our findings provide direct evidence that T[SUB]FH[/SUB] cells play a critical role in vaccine-induced immunity in humans, and suggest a novel strategy to promote such cells by intranasal vaccines against respiratory infections.
Copyright ? 2018 Aljurayyan et al.
PMID: 29563292 DOI: 10.1128/JVI.00114-18
[h=1]Activation and induction of antigen-specific T follicular helper cells (TFH) play a critical role in LAIV-induced human mucosal anti-influenza antibody response.[/h] Aljurayyan A[SUP]1[/SUP], Puksuriwong S[SUP]1[/SUP], Ahmed M[SUP]1[/SUP], Sharma R[SUP]2[/SUP], Krishnan M[SUP]2[/SUP], Sood S[SUP]2[/SUP], Davies K[SUP]3[/SUP], Rajashekar D[SUP]3[/SUP], Leong S[SUP]4[/SUP], McNamara PS[SUP]5[/SUP], Gordon S[SUP]6[/SUP], Zhang Q[SUP]7[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] There is increasing interest recently in developing intranasal vaccines against respiratory tract infections. Antibody response is critical in vaccine-induced protection and T[SUB]FH[/SUB] is considered important in mediating antibody response. Most data supporting the role for T[SUB]FH[/SUB] in antibody response are from animal studies, and direct evidence from humans is limited, apart from T[SUB]FH[/SUB]-like cells in blood. We studied activation and induction of T[SUB]FH[/SUB] and its role on anti-influenza antibody response by live-attenuated influenza vaccine(LAIV) in human nasopharynx-associated lymphoid tissue(NALT). T[SUB]FH[/SUB] activation in adenotonsillar tissues were analysed by flow-cytometry, and anti-hemagglutinin(HA) antibodies examined following LAIV stimulation of tonsillar mononuclear cells(MNC). Induction of antigen-specific T[SUB]FH[/SUB] by LAIV was studied by flow-cytometry for induced T[SUB]FH[/SUB] and CD154 expression. LAIV induced T[SUB]FH[/SUB] proliferation which correlated with anti-HA antibody production, and T[SUB]FH[/SUB] was shown critical for antibody response. Induction of T[SUB]FH[/SUB] from na?ve T cells by LAIV was shown in newly induced T[SUB]FH[/SUB] expressing BCL6 and CD21, which was followed by the detection of anti-HA antibodies. Antigen specificity of LAIV-induced T[SUB]FH[/SUB] was demonstrated by the expression of antigen-specific T cell activation marker CD154 upon challenge by H1N1 virus antigen or HA. LAIV-induced T[SUB]FH[/SUB] differentiation was inhibited by BCL6, IL21, ICOS and CD40 signalling blocking respectively, and that diminished anti-HA antibody production.
[h=4]CONCLUSION:[/h] We demonstrate for the first time the induction of antigen-specific T[SUB]FH[/SUB] by LAIV in human NALT that provide critical support for anti-influenza antibody response. Promoting antigen-specific T[SUB]FH[/SUB] in NALT by intranasal vaccines may provide an effective vaccination strategy against respiratory infections in humans.IMPORTANCE. Airway infection such as influenza is common in humans. Intranasal vaccination has been considered a more biologically relevant and effective way of immunization against airway infection. Vaccine-induced antibody response is crucial for protection against infection. Recent data from animal studies suggest one type of T cells, named T[SUB]FH[/SUB] is important for the antibody response. However, data on whether this T[SUB]FH[/SUB]-mediated help for antibody production operates in humans is limited, due to the lack of access to human immune tissue containing the T[SUB]FH[/SUB] In this study, we demonstrated the induction of T[SUB]FH[/SUB] cells by an intranasal influenza vaccine in human immune tissue that provide critical support for anti-influenza antibody response. Our findings provide direct evidence that T[SUB]FH[/SUB] cells play a critical role in vaccine-induced immunity in humans, and suggest a novel strategy to promote such cells by intranasal vaccines against respiratory infections.
Copyright ? 2018 Aljurayyan et al.
PMID: 29563292 DOI: 10.1128/JVI.00114-18