Notch–RBP-J signaling controls the homeostasis of CD8− dendritic cells in the spleen

Caton, Michele L.; Smith-Raska, Matthew; Reizis, Boris

doi:10.1084/jem.20062648

Cited by 756 publications

(865 citation statements)

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“…CD4-Cre 1/À IFNAR flox/flox [9] and LysM-Cre 1/À IFNAR flox/flox mice [27] have been described earlier. CD11c-Cre 1/À IFNAR flox/flox mice were obtained by intercrossing CD11c-Cre 1 mice [46] with IFNAR flox/ flox mice [9]. ISRE-eGFP mice express eGFP under the control of an ISRE (Michaël G. Tovey, unpublished data).…”

Section: Methodsmentioning

confidence: 99%

Concomitant type I IFN receptor‐triggering of T cells and of DC is required to promote maximal modified vaccinia virus Ankara‐induced T‐cell expansion

et al. 2010

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Clinical Infection Research; a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, Braunschweig; Hannover, Germany Virus-induced expansion of CD8 1 T cells may be promoted by type I IFN receptor (IFNAR)-triggering of T cells, depending on the pathogen tested. We studied modified vaccinia virus Ankara (MVA), a promising vaccine vector candidate, which was derived from conventional vaccinia virus (VACV) by more than 570 consecutive in vitro passages. In adoptive transfer experiments, we verified that VACV expressing the gp33 epitope of lymphocytic choriomeningitis virus (VACV gp33 ) induced largely IFNAR-independent expansion of gp33-specific T cells. On the contrary, MVA gp33 -induced T-cell expansion was IFNAR dependent. Interestingly, under the latter conditions, T-cell activation was IFNAR independent, whereas T-cell apoptosis was enhanced in the absence of IFNAR. To address whether MVA-induced T-cell expansion was solely affected by IFNAR-triggering of T cells, expansion of endogenous T cells was studied in conditional mice with a T-cell-or DC-specific IFNAR deletion. Interestingly, both mouse strains showed moderately reduced T-cell expansion, whereas mice with a combined T-cell-and DC-specific IFNAR ablation showed massively reduced T-cell expansion similar to that of IFNAR À/À mice. These results are compatible with the model that IFN-inducing viruses such as MVA confer virus-specific CD8 1 T-cell expansion by concomitant IFNAR-triggering of DC and of T cells.Key words: CD8 1 T-cell expansion . Modified vaccinia virus Ankara . Type I IFN IntroductionInfection with many different viruses induces rapid type I IFN responses that are detectable in serum within hours. IFN constitutes a family of cytokines with 14 IFN-a, one IFN-b subtype, and a number of other subclasses including . All IFN bind to one common heterodimeric receptor consisting of an a-chain (type I IFN receptor, IFNAR1) and a b-chain (IFNAR2). IFNAR-triggering results in phosphorylation of STAT1 and STAT2 transcription factors and the induction of at least 200 different target genes [2,3]. Although most cell lines show IFN expression upon in vitro infection, [7][8][9]. In particular, several studies reported IFN-mediated effects on T-cell responses [10,11]. In one report, lack of direct IFNAR-signaling on the level of CD8 1 T cells was associated with reduced expansion of gp33-specific T cells upon infection with lymphocytic choriomeningitis virus (LCMV). This phenomenon was less pronounced upon infection with VACV gp33 [12]. Interestingly, instead of enhancing T-cell function, IFN can also lead to T-cell attrition or activation induced cell death [13,14].To further study the impact of virus-induced IFN on the stimulation of virus-specific T-cell responses, we analyzed expansion of antigen-specific T cells upon infection with two closely related viruses, vaccinia virus (VACV) and modified vaccinia virus Ankara (MVA), which upon infection either suppress or induce IFN responses, respectively. VACV d...

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Section: Methodsmentioning

confidence: 99%

Concomitant type I IFN receptor‐triggering of T cells and of DC is required to promote maximal modified vaccinia virus Ankara‐induced T‐cell expansion

et al. 2010

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“…One possibility is the use of a Cre-loxP technology-based approach, which will profit from the recent generation of mice that efficiently express a Cre recombinase BAC transgene in CD11c high DC. 33 Furthermore, DC ablation strategies might get more refined given the numerous ongoing gene expression profiling studies that could reveal uniquely expressed genes within the DC compartment.…”

Section: Targeting Conventional Dc: the Cd11c-dtr Transgenic Micementioning

confidence: 99%

Probing in vivo dendritic cell functions by conditional cell ablation

Sapoznikov

2008

Immunol Cell Biol

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Dendritic cells (DCs) play a central role in T-cell activation and the control of the inherent autoreactivity of the T-cell compartment. Pleiotropic DC functions are likely associated with discrete DC subsets. However, the latter remain largely defined by phenotype and unique anatomic location, rather than function. The investigation of DC involvement in complex phenomena that rely on multicellular interactions, such as immuno-stimulation and tolerization calls for an assessment of DC functions within physiological context. Given the highly dynamic DC compartment, the method of choice to study in vivo DC functions is their conditional ablation in the intact organism. Here, we summarize the recent progress in this field highlighting pitfalls and prospects of the approach.

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“…Other genes, i.e. Krüppel family of zinc finger transcription factor Ikaros C, transcription factor PU.1, IRF-2 and IRF-4 (IFN regulatory factor-2 and -4), Notch-dependent transcription factor RBP-J, and TRAF6 (TNF receptor associated factor-6), have also been described to play a role in differentiation of CD4+ DC subset [36][37][38][39][40][41]. The Ig superfamily member, CD40 and Toll-like receptors are receptors known to signal through TRAF6, yet none of those TNFR are implicated in the regulation of DC homeostasis.…”

Section: Noncanonical Nfκb Signaling Cascade Regulates DC Homeostasismentioning

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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Notch–RBP-J signaling controls the homeostasis of CD8− dendritic cells in the spleen

Cited by 756 publications

References 45 publications

Concomitant type I IFN receptor‐triggering of T cells and of DC is required to promote maximal modified vaccinia virus Ankara‐induced T‐cell expansion

Concomitant type I IFN receptor‐triggering of T cells and of DC is required to promote maximal modified vaccinia virus Ankara‐induced T‐cell expansion

Probing in vivo dendritic cell functions by conditional cell ablation

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

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