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Interleukin-6 is crucial for recall of influenza-specific memory CD4 T cells.

Longhi MP, Wright K, Lauder SN, Nowell MA, Jones GW, Godkin AJ, Jones SA, Gallimore AM - PLoS Pathog. (2008)

Bottom Line: Specifically, we find that CD4+ but not CD8+ T cell memory is critically dependent upon IL-6.This effect of IL-6 includes its ability to suppress CD4+CD25+ regulatory T cells (Treg).We demonstrate that influenza-induced IL-6 limits the activity of virus-specific Tregs, thereby facilitating the activity of virus-specific memory CD4+ T cells.

View Article: PubMed Central - PubMed

Affiliation: Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.

ABSTRACT
Currently, our understanding of mechanisms underlying cell-mediated immunity and particularly of mechanisms that promote robust T cell memory to respiratory viruses is incomplete. Interleukin (IL)-6 has recently re-emerged as an important regulator of T cell proliferation and survival. Since IL-6 is abundant following infection with influenza virus, we analyzed virus-specific T cell activity in both wild type and IL-6 deficient mice. Studies outlined herein highlight a novel role for IL-6 in the development of T cell memory to influenza virus. Specifically, we find that CD4+ but not CD8+ T cell memory is critically dependent upon IL-6. This effect of IL-6 includes its ability to suppress CD4+CD25+ regulatory T cells (Treg). We demonstrate that influenza-induced IL-6 limits the activity of virus-specific Tregs, thereby facilitating the activity of virus-specific memory CD4+ T cells. These experiments reveal a critical role for IL-6 in ensuring, within the timeframe of an acute infection with a cytopathic virus, that antigen-specific Tregs have no opportunity to down-modulate the immune response, thereby favoring pathogen clearance and survival of the host.

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Related in: MedlinePlus

IL-6 production post-infection with influenza virus.WT mice were infected i.n. with 20 HAU H17 influenza virus. Three and eight days after infection, serum levels of IL-6, IL-10, MCP-1/CCL2, IFN-γ, TNF-α, and IL-12 were measured in uninfected (A) and infected (B) mice by Cytometric Bead Array.
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ppat-1000006-g001: IL-6 production post-infection with influenza virus.WT mice were infected i.n. with 20 HAU H17 influenza virus. Three and eight days after infection, serum levels of IL-6, IL-10, MCP-1/CCL2, IFN-γ, TNF-α, and IL-12 were measured in uninfected (A) and infected (B) mice by Cytometric Bead Array.

Mentions: We assessed whether IL-6 is produced following infection of mice with influenza virus. Serum, removed from WT mice infected intranasally 3 and 8 days earlier with 20 haemagglutination units (HAU) of influenza virus, was assessed by Cytometric Bead Array. This method of analysis allowed us to compare serum levels of IL-6, IL-10, MCP-1, IFNγ, TNFα and IL-12 in the infected mice. The results, shown in Figure 1, indicate a selective elevation in IL-6 secretion in the serum at these time-points. IL-6 levels returned to baseline levels following the establishment of the memory phase of the infection (data not shown). Since IL-6 production was prominent during the acute phase of infection and within the timeframe of virus specific T cell activation we considered it reasonable to hypothesize that IL-6 plays a role in shaping the T cell response to influenza virus.


Interleukin-6 is crucial for recall of influenza-specific memory CD4 T cells.

Longhi MP, Wright K, Lauder SN, Nowell MA, Jones GW, Godkin AJ, Jones SA, Gallimore AM - PLoS Pathog. (2008)

IL-6 production post-infection with influenza virus.WT mice were infected i.n. with 20 HAU H17 influenza virus. Three and eight days after infection, serum levels of IL-6, IL-10, MCP-1/CCL2, IFN-γ, TNF-α, and IL-12 were measured in uninfected (A) and infected (B) mice by Cytometric Bead Array.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2279258&req=5

ppat-1000006-g001: IL-6 production post-infection with influenza virus.WT mice were infected i.n. with 20 HAU H17 influenza virus. Three and eight days after infection, serum levels of IL-6, IL-10, MCP-1/CCL2, IFN-γ, TNF-α, and IL-12 were measured in uninfected (A) and infected (B) mice by Cytometric Bead Array.
Mentions: We assessed whether IL-6 is produced following infection of mice with influenza virus. Serum, removed from WT mice infected intranasally 3 and 8 days earlier with 20 haemagglutination units (HAU) of influenza virus, was assessed by Cytometric Bead Array. This method of analysis allowed us to compare serum levels of IL-6, IL-10, MCP-1, IFNγ, TNFα and IL-12 in the infected mice. The results, shown in Figure 1, indicate a selective elevation in IL-6 secretion in the serum at these time-points. IL-6 levels returned to baseline levels following the establishment of the memory phase of the infection (data not shown). Since IL-6 production was prominent during the acute phase of infection and within the timeframe of virus specific T cell activation we considered it reasonable to hypothesize that IL-6 plays a role in shaping the T cell response to influenza virus.

Bottom Line: Specifically, we find that CD4+ but not CD8+ T cell memory is critically dependent upon IL-6.This effect of IL-6 includes its ability to suppress CD4+CD25+ regulatory T cells (Treg).We demonstrate that influenza-induced IL-6 limits the activity of virus-specific Tregs, thereby facilitating the activity of virus-specific memory CD4+ T cells.

View Article: PubMed Central - PubMed

Affiliation: Medical Biochemistry and Immunology, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom.

ABSTRACT
Currently, our understanding of mechanisms underlying cell-mediated immunity and particularly of mechanisms that promote robust T cell memory to respiratory viruses is incomplete. Interleukin (IL)-6 has recently re-emerged as an important regulator of T cell proliferation and survival. Since IL-6 is abundant following infection with influenza virus, we analyzed virus-specific T cell activity in both wild type and IL-6 deficient mice. Studies outlined herein highlight a novel role for IL-6 in the development of T cell memory to influenza virus. Specifically, we find that CD4+ but not CD8+ T cell memory is critically dependent upon IL-6. This effect of IL-6 includes its ability to suppress CD4+CD25+ regulatory T cells (Treg). We demonstrate that influenza-induced IL-6 limits the activity of virus-specific Tregs, thereby facilitating the activity of virus-specific memory CD4+ T cells. These experiments reveal a critical role for IL-6 in ensuring, within the timeframe of an acute infection with a cytopathic virus, that antigen-specific Tregs have no opportunity to down-modulate the immune response, thereby favoring pathogen clearance and survival of the host.

Show MeSH
Related in: MedlinePlus