Steady-state and inflammatory dendritic-cell development

Shortman, Ken; Naik, Shalin H.

doi:10.1038/nri1996

Cited by 1,049 publications

(1,179 citation statements)

References 129 publications

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“…These DC are likely to result from the maturation and migration of peripheral DC following interaction with IC31. We may not exclude that some vaccineassociated DC originated from macrophages that internalized vaccine components at the site of immunization and subsequently matured into DC [19].…”

Section: Discussionmentioning

confidence: 99%

Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

et al. 2008

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Vaccine efficacy largely depends upon DC targeting and activation. The most potent TLR soluble ligands induce diffuse DC activation, which may be associated with marked pro‐inflammatory responses and possibly adverse effects. This raises the concern that effective vaccine adjuvants may similarly rely on widespread DC activation. Using a promising candidate vaccine against tuberculosis (fusion protein of Ag85B and 6‐kDa early secretory antigenic target (ESAT‐6)) formulated in the potent IC31® adjuvant, DC targeting and activation was studied in vivo, following the fate of antigen and adjuvant in the draining lymph nodes, to define the magnitude of DC targeting/activation required in vivo to induce protective vaccine responses. Unexpectedly, protective IFN‐γ‐mediated Ag85B‐ESAT‐6/IC31® responses were associated to the activation of a minute population (less than 0.3%) of CD11c+ lymph node DC, without detectable systemic pro‐inflammatory responses. This activated peripheral tissue‐derived DC population, characterized by enhanced CD80, CD86, CD40 and IL‐12p40 expression, was only identified when focusing on adjuvant‐ or antigen‐labeled CD11c+ DC, which were found to support T cell proliferation. Immunization with aluminum hydroxide adjuvant (Alum) resulted in a similar proportion of antigen‐associated DC but without detectable enhancement of CD80, CD86, CD40 or IL‐12p40 expression. Thus, potent protective IFN‐γ‐producing responses may be elicited by the exquisite activation of a minute number of in vivo targeted DC.

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Section: Discussionmentioning

confidence: 99%

Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

et al. 2008

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“…For example, two broad classes of DC are the peripheral migratory DC and the lymphoid tissue-resident DC [1]. The migratory DC, i.e.…”

Section: Dendritic Cellsmentioning

confidence: 99%

The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis

Trez

Ware

2008

Cytokine & Growth Factor Reviews

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Dendritic cells (DC) constitute the most potent antigen presenting cells of the immune system, playing a key role bridging innate and adaptive immune responses. Specialized DC subsets differ depending on their origin, tissue location and the influence of trophic factors, the latter remain to be fully understood. Stromal cell and myeloid-associated Lymphotoxin-β receptor (LTβR) signaling is required for the local proliferation of lymphoid tissue DC. This review focuses the LTβR signaling cascade as a crucial positive trophic signal in the homeostasis of DC subsets. The noncanonical coreceptor pathway comprised of the Immunoglobulin (Ig) superfamily member, B and T lymphocyte attenuator (BTLA) and TNFR superfamily member, Herpesvirus entry mediator (HVEM) counter regulates the trophic signaling by LTβR. Together both pathways form an integrated signaling circuit achieving homeostasis of DC subsets.Keywords dendritic cells; homeostasis; TNF superfamily; cosignaling; lymphotoxin; herpesvirus entry mediator Dendritic CellsDendritic cells (DC) originate from hematopoietic precursors and can be divided in several subsets depending on their anatomical location, surface phenotype and function. For example, two broad classes of DC are the peripheral migratory DC and the lymphoid tissue-resident DC [1]. The migratory DC, i.e. the dermal DC and Langerhans cells, can be considered as sentinels of the immune system as they form a sensing barrier in peripheral tissues at the interface with environment. The lymphoid tissue-resident DC include the splenic and thymic DC.Dendritic cells are specialized in the capture, transport, processing and presentation of antigens. In the presence of a microbial stimulus, these steps are associated with further DC differentiation (maturation) characterized by upregulation of costimulatory and major histocompatibility complex (MHC) molecules. As DC become activated they migrate to or Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Both spleen and lymph node lymphoid tissue-resident DC possess a half-life of about three days. Despite their rapid turnover, little is known about the factors controlling immediate precursors and homeostasis in vivo. In earlier studies, CD8α expression was used to distinguish between "lymphoid" and "myeloid" DC. However, more recent experiments showed that different DC subsets could differentiate from both lymphoid and myeloid precursors [6,7]. CD8α marker remains very useful to discriminate between subsets, but no longer defines a subset origin. Recently, the group of Shortman provided in vivo and in vitro evidence fo...

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“…components of vaccines, on MHC class I molecules to CD8 + T cells. This process is termed crosspresentation [2,3], and, in mice, this task is most efficiently performed by conventional CD8a + (=CD24 + ) DC [4,5] (according to the Shortman classification [6]). Signal 2, i.e.…”

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confidence: 99%

CD11c: Not merely a murine DC marker, but also a useful vaccination target

Kurts

2008

Eur J Immunol

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The induction of robust CD4 + and CD8 + T cell responses is a central aim in antiviral and anticancer vaccination. To this end, dendritic cells (DC) need to capture the vaccine, process and present it on MHC class I and II molecules. The mechanisms by which DC acquire antigen predetermine the quantity and quality of the ensuing T cell activation. In this issue of the European Journal of Immunology, it is demonstrated that targeting antigen towards CD11c, an integrin expressed preferentially by murine DC, facilitates efficient CD4 + and CD8 + T cell activation. The underlying mechanisms involve efficient antigen delivery into the marginal zone and T/DC zone of the spleen. This commentary discusses these findings in the context of current knowledge on antigen presentation.

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Steady-state and inflammatory dendritic-cell development

Cited by 1,049 publications

References 129 publications

Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

The TNF receptor and Ig superfamily members form an integrated signaling circuit controlling dendritic cell homeostasis

CD11c: Not merely a murine DC marker, but also a useful vaccination target

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