Interleukin-6 Is Crucial for Recall of Influenza-Specific Memory CD4+ T Cells

Longhi, M. Paula; Wright, Kate; Lauder, Sarah N.; Nowell, Mari Ann; Jones, Gareth Wyn; Godkin, Andrew; Jones, Simon A.; Gallimore, Awen

doi:10.1371/journal.ppat.1000006

Cited by 93 publications

(82 citation statements)

References 31 publications

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“…Data presented herein build upon these studies and highlight three key observations relating to the IL-6 control of local T cell responses. First, consistent with previous reports, IL-6-deficient mice displayed significantly reduced T cell recruitment following acute or repeated inflammatory activation (9,33,47). However, the impaired T cell infiltration was not selective for IL-17A-secreting T cells; it also affected IFN-g-secreting T cells.…”

Section: Discussionsupporting

confidence: 91%

Loss of CD4+ T Cell IL-6R Expression during Inflammation Underlines a Role for IL-6TransSignaling in the Local Maintenance of Th17 Cells

Jones

McLoughlin

Hammond

et al. 2010

The Journal of Immunology

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166

138

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IL-6 responses are classically orchestrated via a membrane-bound IL-6R (CD126) α subunit (classical IL-6R signaling) or through a soluble form of this cognate receptor (IL-6 trans signaling). Appraisal of IL-6R expression on human and mouse T cells emphasized that IL-6R expression is closely linked with that of CCR7 and CD62L. In this regard, infiltrating effector T cells from clinical and experimental peritonitis episodes lose IL-6R expression, and anti-CD3/CD28 Ab costimulation of peripheral T cells in vitro leads to a downregulation in IL-6R expression. Consequently, IL-6 signaling through membrane-bound IL-6R seems to be limited to naive or central memory T cell populations. Loss of IL-6R expression by activated T cells further suggests that these effector cells might still retain IL-6 responsiveness via IL-6 trans signaling. Using IL-6R–deficient mice and recombinant tools that modulate the capacity of IL-6 to signal via its soluble receptor, we report that local control of IL-6 trans signaling regulates the effector characteristics of the T cell infiltrate and promotes the maintenance of IL-17A–secreting CD4+ T cells. Therefore, we concluded that classical IL-6R signaling in naive or central memory CD4+ T cells is required to steer their effector characteristics, whereas local regulation of soluble IL-6R activity might serve to maintain the cytokine profile of the Th cell infiltrate. Therefore, the activation status of a T cell population is linked with an alteration in IL-6 responsiveness.

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Section: Discussionsupporting

confidence: 91%

Loss of CD4+ T Cell IL-6R Expression during Inflammation Underlines a Role for IL-6TransSignaling in the Local Maintenance of Th17 Cells

Jones

McLoughlin

Hammond

et al. 2010

The Journal of Immunology

Self Cite

166

138

View full text Add to dashboard Cite

show abstract

“…Thus, IL-6 could contribute to tissue destruction in inflammatory disease through its effect on CD4 T cell cytokine production (Figure 1). IL-6 participates in the development of memory CD4 T cells, against influenza [84]. It is therefore possible that IL-6 also helps to maintain survival or homeostasis of autoreactive CD4 T cells and contribute to the persistence of these cells in chronic inflammatory diseases.…”

Section: Reviewmentioning

confidence: 99%

Interleukin-6: from an inflammatory marker to a target for inflammatory diseases

Rincón

2012

Trends in Immunology

296

200

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“…However, with the demise of the suppressor T-cell concept during recent decades, the role of Treg cells in IAV infection and, more specifically, their mechanism of action, remained unexplored. More-recent studies have implicated Treg cells in impairing the induction of CD8 ϩ T cells by IAV vaccination (18) and of CD4 ϩ T cell memory by IAV infection specifically in IL-6-deficient mice (34). However, a potential involvement of Treg cells in the development of IAVinduced pathology was not investigated.…”

Section: Treg Cells In Total Cd4mentioning

confidence: 99%

Suppression of Innate Immune Pathology by Regulatory T Cells during Influenza A Virus Infection of Immunodeficient Mice

Antunes¹,

Kassiotis²

2010

J Virol

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The viral infection of higher vertebrates elicits potent innate and adaptive host immunity. However, an excessive or inappropriate immune response also may lead to host pathology that often is more severe than the direct effects of viral replication. Therefore, several mechanisms exist that regulate the magnitude and class of the immune response. Here, we have examined the potential involvement of regulatory T (Treg) cells in limiting pathology induced by influenza A virus (IAV) infection. Using lymphocyte-deficient mice as hosts, we showed that Treg cell reconstitution resulted in a significant delay in weight loss and prolonged survival following infection. The adoptively transferred Treg cells did not affect the high rate of IAV replication in the lungs of lymphocyte-deficient hosts, and therefore their disease-ameliorating effect was mediated through the suppression of innate immune pathology. Mechanistically, Treg cells reduced the accumulation and altered the distribution of monocytes/macrophages in the lungs of IAV-infected hosts. This reduction in lung monocytosis was associated with a specific delay in monocyte chemotactic protein-2 (MCP-2) induction in the infected lungs. Nevertheless, Treg cells failed to prevent the eventual development of severe disease in lymphocyte-deficient hosts, which likely was caused by the ongoing IAV replication. Indeed, using T-cell-deficient mice, which mounted a T-cell-independent B cell response to IAV, we further showed that the combination of virusneutralizing antibodies and transferred Treg cells led to the complete prevention of clinical disease following IAV infection. Taken together, these results suggested that innate immune pathology and virus-induced pathology are the two main contributors to pathogenesis during IAV infection.

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Interleukin-6 Is Crucial for Recall of Influenza-Specific Memory CD4+ T Cells

Cited by 93 publications

References 31 publications

Loss of CD4+ T Cell IL-6R Expression during Inflammation Underlines a Role for IL-6TransSignaling in the Local Maintenance of Th17 Cells

Loss of CD4+ T Cell IL-6R Expression during Inflammation Underlines a Role for IL-6TransSignaling in the Local Maintenance of Th17 Cells

Interleukin-6: from an inflammatory marker to a target for inflammatory diseases

Suppression of Innate Immune Pathology by Regulatory T Cells during Influenza A Virus Infection of Immunodeficient Mice

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