Influenza A Infection Enhances Cross-Priming of CD8+ T Cells to Cell-Associated Antigens in a TLR7- and Type I IFN-Dependent Fashion

Wei, Joe; Waithman, Jason; Lata, Roleen; Mifsud, Nicole A.; Cebon, Jonathan; Kay, Thomas W. H.; Smyth, Mark J.; Sadler, Anthony John; Chen, Weisan

doi:10.4049/jimmunol.1002129

Cited by 29 publications

(34 citation statements)

References 69 publications

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“…Recent studies have suggested that type I IFN enhances the CD8 + T cell response during antigen cross-presentation [17], [22], [40], [41]. To evaluate whether the temporal effect of type I IFN signaling on CD8 + T cell responses occurred in mice with impaired cross-presentation capacity, we utilized BATF3 -/- mice, which lack CD8-α and CD103 + dendritic cells [18], [42].…”

Section: Resultsmentioning

confidence: 99%

A Temporal Role Of Type I Interferon Signaling in CD8+ T Cell Maturation during Acute West Nile Virus Infection

et al. 2011

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A genetic absence of the common IFN- α/β signaling receptor (IFNAR) in mice is associated with enhanced viral replication and altered adaptive immune responses. However, analysis of IFNAR-/- mice is limited for studying the functions of type I IFN at discrete stages of viral infection. To define the temporal functions of type I IFN signaling in the context of infection by West Nile virus (WNV), we treated mice with MAR1-5A3, a neutralizing, non cell-depleting anti-IFNAR antibody. Inhibition of type I IFN signaling at or before day 2 after infection was associated with markedly enhanced viral burden, whereas treatment at day 4 had substantially less effect on WNV dissemination. While antibody treatment prior to infection resulted in massive expansion of virus-specific CD8+ T cells, blockade of type I IFN signaling starting at day 4 induced dysfunctional CD8+ T cells with depressed cytokine responses and expression of phenotypic markers suggesting exhaustion. Thus, only the later maturation phase of anti-WNV CD8+ T cell development requires type I IFN signaling. WNV infection experiments in BATF3 -/- mice, which lack CD8-α dendritic cells and have impaired priming due to inefficient antigen cross-presentation, revealed a similar effect of blocking IFN signaling on CD8+ T cell maturation. Collectively, our results suggest that cell non-autonomous type I IFN signaling shapes maturation of antiviral CD8+ T cell response at a stage distinct from the initial priming event.

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Section: Resultsmentioning

confidence: 99%

A Temporal Role Of Type I Interferon Signaling in CD8+ T Cell Maturation during Acute West Nile Virus Infection

et al. 2011

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“…Type I IFN stimulates effector T cells, as well as DCs, promoting their maturation and survival and the enhancement of DC crosspresentation (35)(36)(37)45). For example, the coinjection of a high dose of soluble IFN-a/b plus Ag (35) or the injection of DCtargeted DEC205-binding Ag in combination with the IFN-a/b inducer polyinosinic:polycytidylic acid (36) stimulates T cell priming.…”

Section: Discussionmentioning

confidence: 99%

Invariant NKT Cells Induce Plasmacytoid Dendritic Cell (DC) Cross-Talk with Conventional DCs for Efficient Memory CD8+ T Cell Induction

Shimizu

Asakura

Shinga

et al. 2013

The Journal of Immunology

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A key goal of vaccine immunotherapy is the generation of long-term memory CD8+ T cells capable of mediating immune surveillance. We discovered a novel intercellular pathway governing the development of potent memory CD8+ T cell responses against cell-associated Ags that is mediated through cross-presentation by XCR1+ dendritic cells (DCs). Generation of CD8+ memory T cells against tumor cells pulsed with an invariant NKT cell ligand depended on cross-talk between XCR1+ and plasmacytoid DCs that was regulated by IFN-α/IFN-αR signals. IFN-α production by plasmacytoid DCs was stimulated by an OX40 signal from the invariant NKT cells, as well as an HMGB1 signal from the dying tumor cells. These findings reveal a previously unknown pathway of intercellular collaboration for the generation of tumor-specific CD8+ memory T cells that can be exploited for strategic vaccination in the setting of tumor immunotherapy.

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“…Hemagglutination inhibition (HI) assay serum samples were treated with receptor-destroying enzyme (RDE; Denka Seiken Co., Tokyo, Japan) overnight at 37°C, followed by heat inactivation (56°C for 30 min). Serially diluted sera in V-bottom 96-well plates were tested in duplicate for their ability to inhibit the agglutination of 0.5% turkey red blood cells by 4 HAU of PR8 or Cal/08 virus in a standard HI assay as described previously (60). Numbers were converted to a log 2 scale to determine statistical significance.…”

Section: Methodsmentioning

confidence: 99%

TLR7 Recognition Is Dispensable for Influenza Virus A Infection but Important for the Induction of Hemagglutinin-Specific Antibodies in Response to the 2009 Pandemic Split Vaccine in Mice

Jeisy-Scott

Kim

Davis

et al. 2012

J Virol

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Recognition of pathogen-associated molecular patterns by pattern recognition receptors of the innate immune system is crucial for the initiation of innate and adaptive responses and for immunological memory. We investigated the role of TLR7 in the induction of adaptive immunity and long-term memory following influenza virus infection and vaccination in C57BL/6 mice. During infection with influenza A/PR8/34 virus, the absence of either TLR7 or MyD88 leads to reduced virus-specific antibodies in the serum and antibody-secreting cells in their secondary lymphoid organs, particularly in bone marrow. In spite of this, the absence of TLR7/MyD88 signaling did not impair the production of protective antibodies. Following immunization with the 2009 pandemic inactivated split vaccine, TLR7 −/− mice had significantly lower levels of germinal center formation, antibody-secreting cells, and circulating influenza virus-specific antibodies than control animals. Consequently, TLR7 −/− mice failed to develop protective immunological memory upon challenge. Furthermore, the immunogenicity of the split vaccine was likely due to TLR7 recognition of virion RNA, as its removal from the split vaccine significantly reduced the levels of influenza virus-specific antibodies and compromised the vaccine protective efficacy in mice. Taken together, our data demonstrate that TLR7 plays an important role in vaccine-induced humoral immune responses to influenza virus through the interaction with viral RNA present in the split vaccine.

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Influenza A Infection Enhances Cross-Priming of CD8+ T Cells to Cell-Associated Antigens in a TLR7- and Type I IFN-Dependent Fashion

Cited by 29 publications

References 69 publications

A Temporal Role Of Type I Interferon Signaling in CD8+ T Cell Maturation during Acute West Nile Virus Infection

A Temporal Role Of Type I Interferon Signaling in CD8+ T Cell Maturation during Acute West Nile Virus Infection

Invariant NKT Cells Induce Plasmacytoid Dendritic Cell (DC) Cross-Talk with Conventional DCs for Efficient Memory CD8+ T Cell Induction

TLR7 Recognition Is Dispensable for Influenza Virus A Infection but Important for the Induction of Hemagglutinin-Specific Antibodies in Response to the 2009 Pandemic Split Vaccine in Mice

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