Cutting Edge: Conventional CD8α+ Dendritic Cells Are Preferentially Involved in CTL Priming After Footpad Infection with Herpes Simplex Virus-1

Smith, Christopher M.; Belz, Gabrielle T.; Wilson, Nicholas S.; Villadangos, José A; Shortman, Ken; Carbone, Federico; Heath, William R.

doi:10.4049/jimmunol.170.9.4437

Cited by 167 publications

(181 citation statements)

References 37 publications

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“…This demonstrates that CD8 T cell activation by CD8a + DC is reciprocal and highlights another unique facet of the relationship between CD8 T cells and CD8a + DC. CD8a + DC have been shown to be crucial for priming CD8 T cell responses against viral and intracellular bacterial antigens, which could be processed either via the classical MHC class I pathway or by cross-presentation [40][41][42]. This raises the possibility that our observations may be extended to microbial antigens that are presented by either pathway.…”

Section: Discussionmentioning

confidence: 91%

“…The splenic DC preparation also consisted of about 5% plasmacytoid DC, which were CD11c int , I-Ab -/low and mouse plasmacytoid DC antigen 1 (m-PDCA-1) + . Splenic OT-I CD8 T cells that were freshly isolated or pre-activated with PMA and ionomycin for 2 days were cultured with splenic DC pulsed with either relevant peptide OVA 257-264 or control peptide GP [33][34][35][36][37][38][39][40][41] . After 20 h of co-culture, the expression of CD40, CD80 and CD86 on DC was determined by flow cytometry.…”

Section: Resultsmentioning

confidence: 99%

“…Both freshly isolated and pre-activated CD8 T cells induced OVA 257-264 -pulsed DC, but not GP [33][34][35][36][37][38][39][40][41] -pulsed DC, to up-regulate all of the co-stimulatory molecules tested ( Fig. 1A and B).…”

Section: Resultsmentioning

confidence: 99%

“…It was reported that CD8a + DC are the main producers of IL-12p70 [20,[31][32][33][34]. Furthermore, CD8a + DC are specialized in cross-priming CD8 T cell responses [35][36][37][38][39][40][41][42]. In contrast, other reports have shown that IL-12 can also be produced by CD8a -DC [43,44].…”

Section: Cd40l Is Rapidly Up-regulated By Cd8 T Cellsmentioning

confidence: 99%

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CD40L‐expressing CD8 T cells prime CD8α⁺ DC for IL‐12p70 production

et al. 2008

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CD8a + DC are implicated as the principle DC subset for cross-presentation and crosspriming of cytotoxic CD8 T cell responses. In this study, we demonstrate another unique facet of the CD8a + DC and CD8 T cell relationship, by showing that CD8 T cells reciprocally activate CD8a + DC, but not CD8a -DC, for IL-12p70 production, the key Th1-promoting cytokine. This effect was observed during an antigen-specific interaction between DC and activated CD8 T cells, along with secondary TLR stimulation of DC by LPS. Activated CD8 T cells use a combination of IFN-c and CD40L, which is rapidly up-regulated poststimulation, to prime DC for IL-12p70 production during an antigen-specific response. Our results suggest that the interaction between CD8a + DC and antigen-primed CD8 T cells may form an important component of Th1-mediated immunity through the induction of IL-12p70. Key words: CD8 T cells Á Dendritic cells Á IL-12p70Introduction DC are essential for the activation and polarization of T cells during an adaptive immune response [1,2]. DC respond to stimulatory signals from microbes and inflammatory mediators and mature into professional antigen-presenting cells that prime the adaptive immune system [3,4]. DC activity is also influenced through direct and indirect interaction with other effector immune cells, which results in the delivery of "feedback" signals that can influence the activation status of the DC and thus the outcome of the adaptive immune response [5][6][7]. CD8 T cells are principally known for their role in cytotoxic killing. However, their ability to promote Th1 responses has also been described. In vivo, CD8 T cells have been shown to be essential for the induction of protective Th1 responses against microbial infections [8][9][10]. Likewise, CD8 T cells can also inhibit the development of allergic Th2 IgE responses [11,12]. CD8 T cells can have a direct impact on DC during their interaction, inducing DC to mature [13], and enhancing their Th1-polarizing capabilities by augmenting their ability to produce 14,15].IL-12p70 is a heterodimeric pro-inflammatory cytokine that plays a central role in Th1 immunity, acting on T cells and NK cells by inducing proliferation, cytotoxic function and IFN-c production [16]. IL-12p70 production by DC during T cell priming is crucial for the development of Th1 responses [16][17][18]. Hence, control of DC IL-12p70 production is important for the development of Th1 immunity.Previous reports on CD8 T cell-mediated IL-12p70 production utilized DC generated from monocytes or bone marrow progenitors using 14,15]. These DC are now thought to appear only under inflammatory conditions [19]. They differ markedly from DC that reside in lymphoid organs, and hence do not necessarily reflect events that occur with lymphoid resident DC. Splenic DC comprise of a heterogeneous population of cells with different phenotypes and functional characteristics [20]. It is unknown whether CD8 T cells could possibly modulate IL-12p70 production with splenic resident DC, or whether CD8 T cellme...

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Section: Discussionmentioning

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Cd40l Is Rapidly Up-regulated By Cd8 T Cellsmentioning

confidence: 99%

See 2 more Smart Citations

CD40L‐expressing CD8 T cells prime CD8α⁺ DC for IL‐12p70 production

et al. 2008

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“…In other model systems in which the amount of phagocytosis was controlled, the CD8 + DC subset also showed enhanced cross-presentation compared to CD8 -DC [33,34]. More importantly, the CD8 + DC subset exclusively crosspresents antigens from herpes simplex virus, influenza virus, vaccinia virus, lymphocytic choriomeningitis virus (LCMV) and Listeria monocytogenes after in vivo infection [48][49][50]. Apparently, the CD8 + DC subset is the principal DC type to activate CD8 + T cell responses towards intracellular cytosolic pathogens.…”

Section: Discussionmentioning

confidence: 99%

CD8^– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens

et al. 2008

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Mouse splenic dendritic cell (DC) subsets possess distinct antigen-presentation abilities. CD8 + DC are specialized in cross-presentation of antigens to CD8 + T cells, whereas CD8 -DC are more efficient in antigen presentation to CD4 + T cells. In this study, we examined the capacity of CD8 + and CD8 -DC subsets to present fungal antigens in MHC class I and II molecules to CD8 + and CD4 + T cells, respectively. We used ovalbuminexpressing Saccharomyces cerevisiae (yeast-OVA) as a fungal model system. Both CD8 + and CD8 -DC subsets phagocytosed yeast in equal amounts and uptake was mediated via dectin-1. In addition, both DC subsets induced similar OVA-specific CD4 + T cell proliferation after incubation with yeast-OVA. However, the induction of OVA-specific CD8 + T cell activation was largely restricted to the CD8 -DC subset. Furthermore, only CD8 -DC produced cytokines such as IL-10 and TNF-a and increased IL-23p19 and IL-23p40 mRNA levels in response to yeast. Our results strongly suggest that DC subsets have different functions in the elicitation of adaptive immune responses in vivo. IntroductionFungal infections with pathogenic yeasts such as Candida albicans, Aspergillus fumigatus, Histoplasma capsulatum and Cryptococcus neoformans are a major problem in immunocompromised persons. These opportunistic pathogens usually do not pose problems in healthy individuals, but frequently become invasive in patients suffering from HIV, patients with malignancies or transplant recipients, resulting in life-threatening diseases [1][2][3].Both innate and adaptive immune responses are essential to induce protection against fungi. Dendritic cells (DC) play a central role in the adaptive immune response by capturing fungi and presenting their antigens in major histocompatibility complex (MHC) class I and MHC class II molecules to T cells [4, 5]. DC express a panel of microbial recognition receptors such as Toll-like receptors (TLR) and C-type lectin receptors that are essential for the elicitation of adaptive immune responses [6]. Of these receptors, TLR2 and the DCassociated C-type lectin (dectin-1) are specifically involved in recognition of fungal components [7][8][9]. Zymosan and fungal pathogens like C. albicans and A. fumigatus are sensed by TLR2 that signals via myeloid differentiation factor 88 (MyD88), resulting in NF-jB activation and the production of cytokines [10][11][12][13]. The importance of this signaling cascade can be inferred from the fact that MyD88-knockout mice show an increased susceptibility to fungal infections [14,15].Dectin-1 is expressed on myeloid cells like macrophages, neutrophils, monocytes, and even a subset of T cells [16]. Dectin-1 mediates fungal recognition and Revised 2/11/07 Accepted 11/12/07 [DOI 10.1002/eji.200737647] Key words: Antigen presentation Á Dendritic cell Á Fungal Á T cell Abbreviations: b2m: b2-microglobulin Á Dectin-1: DC-associated C-type lectin-1 Á CR3: complement receptor 3 Á MR: mannose receptor Á SIGNR1: ICAM-3-grabbing nonintegrin (DC-SIGN) homolog, SIGN-related...

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A Systems Biologist's View of Dendritic Cell–Cytotoxic T Lymphocyte Interaction

Ludewig¹,

Bocharov²

2006

Handbook of Dendritic Cells

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Cutting Edge: Conventional CD8α+ Dendritic Cells Are Preferentially Involved in CTL Priming After Footpad Infection with Herpes Simplex Virus-1

Cited by 167 publications

References 37 publications

CD40L‐expressing CD8 T cells prime CD8α⁺ DC for IL‐12p70 production

CD40L‐expressing CD8 T cells prime CD8α⁺ DC for IL‐12p70 production

CD8^– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens

A Systems Biologist's View of Dendritic Cell–Cytotoxic T Lymphocyte Interaction

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Cutting Edge: Conventional CD8α+ Dendritic Cells Are Preferentially Involved in CTL Priming After Footpad Infection with Herpes Simplex Virus-1

Cited by 167 publications

References 37 publications

CD40L‐expressing CD8 T cells prime CD8α+ DC for IL‐12p70 production

CD40L‐expressing CD8 T cells prime CD8α+ DC for IL‐12p70 production

CD8– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens

A Systems Biologist's View of Dendritic Cell–Cytotoxic T Lymphocyte Interaction

Contact Info

Product

Resources

About

CD40L‐expressing CD8 T cells prime CD8α⁺ DC for IL‐12p70 production

CD40L‐expressing CD8 T cells prime CD8α⁺ DC for IL‐12p70 production

CD8^– dendritic cells preferentially cross‐present Saccharomyces cerevisiae antigens