Bone Marrow-Derived IFN-Producing Killer Dendritic Cells Account for the Tumoricidal Activity of Unpulsed Dendritic Cells

Himoudi, Nourredine; Nabarro, Stephen; Buddle, Jo; Eddaoudi, Ayad; Thrasher, Adrian J.; Anderson, John

doi:10.4049/jimmunol.181.9.6654

Cited by 20 publications

(24 citation statements)

References 28 publications

(46 reference statements)

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“…34 Of interest, 5 mouse cancer quantitative trait loci (http://tumor.informatics.jax.org) and Ն 5 of the quantitative trait loci linked to the most frequent human cancers are syntenic to this same distal region of mouse chromosome 7. [47][48][49] Because pre-mNK cells exhibit a prominent antitumoral potential, 14,20,21 it is tempting to speculate that genes defining the proportion of pre-mNK cells also contribute toward defining cancer susceptibility. Indeed, on a per cell basis, the in vivo antitumoral activity of pre-mNK cells is more efficient than mNK cells, 14,16,[20][21][22] probably because of the fact that, as an immediate precursor population, pre-mNK cells can generate a vast number of mNK cells.…”

Section: Ikdc Are Precursors To Mature Nk Cells 4355mentioning

confidence: 99%

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Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation

Guimont-Desrochers

Boucher

Dong

et al. 2012

Blood

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The cell lineage origin of IFN-producing killer dendritic cells (IKDCs), which exhibit prominent antitumoral activity, has been subject to debate. Although IKDCs were first described as a cell type exhibiting both plasmacytoid DC and natural killer (NK) cell properties, the current view reflects that IKDCs merely represent activated NK cells expressing B220, which were thus renamed B220 ؉ NK cells. Herein, we further investigate the lineage relation of B220 ؉ NK cells with regard to other NK-cell subsets. We surprisingly find that, after adoptive transfer, B220 ؊ NK cells did not acquire B220 expression, even in the presence of potent activating stimuli. These findings strongly argue against the concept that B220 IntroductionNatural killer (NK) cells are large granular lymphocytes that were first described for their capacity to spontaneously eliminate tumor cells and virus-infected cells without prior sensitization. 1 These functions are mediated by an array of Ig-like and C-type lectin receptors that deliver both activating and inhibitory signals. 1 In addition to their cytotoxic activity, NK cells rapidly produce vast amounts of cytokines, such as IFN-␥, as well as other cellular mediators, including chemokines. NK cells thus act as an important first line of defense in the early control of virus infection, in tumor immunosurveillance, and in immunoregulation.The differentiation of NK cells from hematopoietic stem cells in the BM is incompletely understood, but it is thought to occur in a sequential manner that involves multiple stages of development that is based on phenotype, function, and turnover. 2 The first committed NK-cell precursor (NKP) is characterized by CD122 ϩ expression in the absence of the expression of other lineage markers, 3 although a pre-NKP cell lacking CD122 expression has recently been characterized as a NK cell-committed progenitor preceding NKP in the differentiation stages. 4 NKPs subsequently give rise to immature NK (iNK) cells that express CD122 along with NK1.1 and CD94/NKG2. As iNK cells differentiate further, they undergo education to achieve their full functional competence, and they acquire CD49b expression to finally become mature NK (mNK) cells. 2 These CD49b ϩ mNK cells still compose a heterogeneous cell population that may be segregated according to their phenotype, function, and tissue distribution. Indeed, functional maturation of CD49b ϩ mNK cells proceeds along 4 stages from the CD11b Ϫ CD27 Ϫ to the CD11b Ϫ CD27 ϩ then to the CD11b ϩ CD27 ϩ and finally to the CD11b ϩ CD27 Ϫ subset. 5 Several other markers are acquired along this differentiation process, including CD43, CD94-NKG2, and Ly49 receptors. [5][6][7] Finally, on activation, mNK cells gain the expression of additional activation markers, namely CD69, CD44, FasL, CD86, and MHC II. [8][9][10][11][12] In addition, activated mNK cells increase in size and show heightened functional properties such as an enhanced cytolytic potential and increased ability to produce cytokines. 2 Notably, activated mNK cells show ...

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Section: Ikdc Are Precursors To Mature Nk Cells 4355mentioning

confidence: 99%

“…Consequently, cells carrying the IKDC phenotype are now more commonly referred to as activated B220 ϩ NK cells. 18 Nevertheless, the exact lineage relation of B220 ϩ NK cells, which arguably present with the most efficient antitumoral potential relative to other mNK-cell subsets, 14,16,[20][21][22] has yet to be determined.…”

Section: Introductionmentioning

confidence: 99%

Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation

Guimont-Desrochers

Boucher

Dong

et al. 2012

Blood

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“…Our previous data showed that IKDCs were present in high amounts in bone marrow DC preparations and that there was an absolute requirement of IKDCs within therapeutic DC preparations to induce a tumor response to unpulsed DCs. We also showed that the tumoricidal activity of BM-IKDCs is lost in hosts lacking functional T cells and NK cells, implying that induction of secondary immune responses is vital for BM-IKDC tumoricidal effects (11).…”

Section: Discussionmentioning

confidence: 80%

“…In adoptive transfer experiments, purified IKDCs from bone marrow (BM-IKDC) were effective at eliminating tumor cells implanted at distant s.c. sites, using a mechanism that is dependent on effector cells of the host immune system (11). We here show that highly purified IKDCs are capable of cross-presenting tumor antigens in vitro and that in vivo cross-presentation occurs during the process of tumor rejection by IKDCs.…”

Section: Cd49bmentioning

confidence: 83%

Migratory and Antigen Presentation Functions of IFN-Producing Killer Dendritic Cells

Himoudi¹,

Yan²,

Bouma

et al. 2009

Cancer Research

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“…[1][2][3][4] In this issue of Blood, Guimont-Desrochers et al redefine B220 ϩ NK cells as a novel intermediate in NK-cell differentiation preceding the acquisition of CD27. 5 …”

Section: Ikdcs or B220 ؉ Nk Cells Are Pre-mnk Cells -----------------mentioning

confidence: 99%

IKDCs or B220+ NK cells are pre-mNK cells

Zitvogel

Housseau²

2012

Blood

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Bone Marrow-Derived IFN-Producing Killer Dendritic Cells Account for the Tumoricidal Activity of Unpulsed Dendritic Cells

Cited by 20 publications

References 28 publications

Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation

Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation

Migratory and Antigen Presentation Functions of IFN-Producing Killer Dendritic Cells

IKDCs or B220+ NK cells are pre-mNK cells

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