Interleukin-2 induces development of dendritic cells from cord blood CD34+ cells

Bykovskaja, S.N.; Buffo, Mary J.; Bunker, Mark; Zhang, Haifan; Majors, Alana K.; Herbert, Mary; Lokshin, Anna; Levitt, Mark L.; Jaja, Andrew; Scalise, Deborah; Kosiban, Deborah; Evans, C. H.; Marks, Stanley; Shogan, Jeffrey

doi:10.1002/jlb.63.5.620

Cited by 23 publications

(24 citation statements)

References 31 publications

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“…If granulocyte͞monocyte colony-stimulating factor is omitted from the cytokine cocktail, DC development becomes IL-7 dependent in vitro (21). In line with these studies, roles for IL-2 (22) or IL-7 (23) in DC development have been proposed. Based on these reports and on the notion that even mature thymic DCs express c-kit (24,25), c-kit-or ␥ c -mediated signals in thymic-DC development had to be considered.…”

Section: Thymic Dcs Can Develop In the Absence Of C-kit-and ␥C-mediatsupporting

confidence: 50%

Developmental dissociation of thymic dendritic cell and thymocyte lineages revealed in growth factor receptor mutant mice

Rodewald¹,

Brocker²,

Haller³

1999

Proc. Natl. Acad. Sci. U.S.A.

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Thymocytes and thymic dendritic cell (DC) lineages develop simultaneously and may originate from a common intrathymic progenitor. Mice deficient for two growth factor receptor molecules [c-kit and the common cytokine receptor ␥ chain (␥c)] lack all thymocytes including T cell progenitors. Despite this lack of pro-T cells, thymic DC compartments were identified in c-kit ؊ ␥c ؊ mice. Thus, c-kit-and ␥c-mediated signals are not essential to generate thymic DCs. In addition, pro-T cells do not appear to be obligatory progenitors of thymic DCs, because DC development is dissociated from the generation of thymocytes in these mice. Thymic DCs in c-kit ؊ ␥c ؊ mice are phenotypically and functionally normal. In contrast to wild-type mice, however, thymic DCs in c-kit ؊ ␥c ؊ and, notably, in RAG-2-deficient mice are CD8␣ neg/low , indicating that CD8␣ expression on thymic DCs is not independent of thymocytes developing beyond the ''RAG-block.''

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Section: Thymic Dcs Can Develop In the Absence Of C-kit-and ␥C-mediatsupporting

confidence: 50%

Developmental dissociation of thymic dendritic cell and thymocyte lineages revealed in growth factor receptor mutant mice

Rodewald¹,

Brocker²,

Haller³

1999

Proc. Natl. Acad. Sci. U.S.A.

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“…The decreased staining with the addition of rhCD122 demonstrated the specificity of the 2RB clone. Furthermore, bone marrow-derived mouse DCs show transcription of the CD122 gene (22) and CD34 + -derived hDCs can express the three IL-2R chains (21). These data are consistent with our findings of the expression of CD122 in hDCs and therefore the highaffinity form of the receptor in mature hDCs.…”

Section: Discussionsupporting

confidence: 92%

“…Whether hDCs express the three chains of IL-2R, in particular CD122 (15,16,(20)(21)(22)(23), remained controversial, so we explored CD132, CD122, and CD25 expression in immature hDCs and after 48-h maturation with different agents: LPS, TNF-a, and the mixture of inflammatory cytokines used by Wuest et al (16) (PGE 2 , IL-6, IL-1b, and TNF-a). CD132 and CD122 were constitutively expressed on immature hDCs, and their expression was not modified with maturation (Fig.…”

Section: Mature Hdcs Express the Three Chains Of Il-2rmentioning

confidence: 99%

IL-2 Phosphorylates STAT5 To Drive IFN-γ Production and Activation of Human Dendritic Cells

Herr

Lemoine

Gouilleux³

et al. 2014

The Journal of Immunology

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Human dendritic cells (hDCs) produce IL-2 and express IL-2R α-chain (CD25), but the role of IL-2 in DC functions is not well defined. A recent study suggested that the main function of CD25 on hDCs was to transpresent IL-2 to activate T lymphocytes. Our results demonstrate the expression of the three chains of the IL-2R on hDCs and that IL-2 induces STAT5 phosphorylation. Interestingly, use of inhibitors of p-STAT5 revealed that IL-2 increases LPS-induced IFN-γ through STAT5 phosphorylation. Finally, we report that IL-2 increases the ability of hDCs to activate helpless CD8+ T cells, most likely because of IL-2–triggered IFN-γ synthesis, as we previously described. For the first time, to our knowledge, we disclose that IL-2 induces monocyte-derived hDC's functional maturation and activation through IL-2R binding. Interestingly, our study suggests a direct effect of anti-CD25 mAbs on hDCs that may contribute to their clinical efficacy.

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“…Given these facts, the role of circulating CD34 + hematopoietic progenitors in primary immune defense seems to be of minor importance, although CD34 + cells are mobilized in an inflammatory response due to the release of various cytokines, e.g., G-CSF, macrophage-CSF (M-CSF), interleukin (IL)-1, and stromal cell-derived factor-1 [20][21][22][23][24]. However, in contrast to quiescent monocytes, hematopoietic progenitors have the potential to proliferate, thereby offering an additional source of replicating dendritic cells.…”

Section: ® Original Articlementioning

confidence: 99%

Tumor Necrosis Factor Alpha‐Stimulated Endothelium: An Inducer of Dendritic Cell Development from Hematopoietic Progenitors and Myeloid Leukemic Cells

et al. 2004

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Especially when exposed to inflammatory stimuli, endothelial cells (EC) have been shown to promote the maturation of monocytes into dendritic cells (DC) and the long-term proliferation of CD34 + cells by constitutive cytokine production and direct cellular contact. We therefore hypothesized that cytokine-stimulated EC would induce hematopoietic progenitor cells to develop into mature dendritic cells. To test this theory, human CD34 + cells derived from cord blood or leukapheresis products were cultured with a monolayer of either interleukin (IL)-1β β, IL-4, or tumor necrosis factor (TNF)-α α-stimulated human umbilical cord EC. The cells in suspension were analyzed weekly over a period of 6 weeks. IL-1β β supported cell expansion, whereas IL-4 had no effect on cell expansion or DC differentiation. Only TNF-α α-stimulated EC induced the development of mature, allostimulatory DC with a high expression of CD83, HLA-DR, CD1a, and costimulatory molecules like CD80 and CD86. Acute myeloid leukemia cells from the cell line Kasumi-1 also developed DC-like features when cocultured with TNF-α α-stimulated EC. Direct contact between endothelial and progenitor cells increased the number of developing DC. Cell cycle analysis and apoptosis studies demonstrated a reduced G 2 M fraction, an increased S fraction, and a decrease in TNF-α α-dependent apoptosis of DC developing in the presence of endothelial cells. As shown by electron and confocal microscopic studies, intimate interactions between EC and DC occurred, resulting in the internalization of the developing DC within the EC monolayer and a bidirectional exchange of proteins. We conclude that, via the action of TNF-α α, inflamed human endothelium can induce CD34 + and leukemic cells to differentiate into dendritic cells.

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Interleukin-2 induces development of dendritic cells from cord blood CD34+ cells

Cited by 23 publications

References 31 publications

Developmental dissociation of thymic dendritic cell and thymocyte lineages revealed in growth factor receptor mutant mice

Developmental dissociation of thymic dendritic cell and thymocyte lineages revealed in growth factor receptor mutant mice

IL-2 Phosphorylates STAT5 To Drive IFN-γ Production and Activation of Human Dendritic Cells

Tumor Necrosis Factor Alpha‐Stimulated Endothelium: An Inducer of Dendritic Cell Development from Hematopoietic Progenitors and Myeloid Leukemic Cells

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