CD34+ Hematopoietic Progenitors from Human Cord Blood Differentiate Along two Independent Dendritic Cell Pathways in Response to GM-CSF+TNFα

Caux, Christophe; Massacrier, Catherine; Vanbervliet, Béatrice; Dubois, Bertrand; B, de Saint-Vis; Dezutter‐Dambuyant, Colette; Jacquet, Christine; Schmitt, Daniel; Banchereau, Jacques

doi:10.1007/978-1-4757-9966-8_4

Cited by 166 publications

(220 citation statements)

References 28 publications

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“…2), as described previously (21). However, in the presence of MSCs, the expression of typical DC Ags, including CD80, CD86, CD83, HLA-DR, and CD40, was strongly reduced (Fig.…”

Section: Mscs Alter Development Of Dcs Derived From Cd34 ϩ Progenitorssupporting

confidence: 81%

“…CD34 ϩ hemopoietic progenitor cells were isolated from umbilical cord blood samples to generate immature DCs as previously described (21). In brief, CD34 ϩ cells were isolated from mononuclear fractions through positive selection using anti-CD34-coated microbeads and Midi-Macs separation columns (Miltenyi Biotec) to a purity of 90-96% as determined by flow cytometry.…”

Section: Generation Of Dcsmentioning

confidence: 99%

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Mesenchymal Stem Cells Inhibit Generation and Function of Both CD34+-Derived and Monocyte-Derived Dendritic Cells

Nauta

Kruisselbrink²,

Lurvink³

et al. 2006

The Journal of Immunology

650

384

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Mesenchymal stem cells (MSCs) are not only able to evade the immune system, but they have also been demonstrated to exert profound immunosuppressive properties on T cell proliferation. However, their effect on the initiators of the immune response, the dendritic cells (DCs), are relatively unknown. In the present study, the effects of human MSCs on the differentiation and function of both CD34+-derived DCs and monocyte-derived DCs were investigated. The presence of MSCs during differentiation blocked the differentiation of CD14+CD1a− precursors into dermal/interstitial DCs, without affecting the generation of CD1a+ Langerhans cells. In line with these observations, MSCs also completely prevented the generation of immature DCs from monocytes. The inhibitory effect of MSCs on DC differentiation was dose dependent and resulted in both phenotypical and functional modifications, as demonstrated by a reduced expression of costimulatory molecules and hampered capacity to stimulate naive T cell proliferation. The inhibitory effect of MSCs was mediated via soluble factors. Taken together, these data demonstrate that MSCs, next to the antiproliferative effect on T cells, have a profound inhibitory effect on the generation and function of both CD34+-derived and monocyte-derived DCs, indicating that MSCs are able to modulate immune responses at multiple levels.

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“…2), as described previously (21). However, in the presence of MSCs, the expression of typical DC Ags, including CD80, CD86, CD83, HLA-DR, and CD40, was strongly reduced (Fig.…”

Section: Mscs Alter Development Of Dcs Derived From Cd34 ϩ Progenitorssupporting

confidence: 81%

Section: Generation Of Dcsmentioning

confidence: 99%

Mesenchymal Stem Cells Inhibit Generation and Function of Both CD34+-Derived and Monocyte-Derived Dendritic Cells

Nauta

Kruisselbrink²,

Lurvink³

et al. 2006

The Journal of Immunology

650

384

View full text Add to dashboard Cite

show abstract

“…They also exhibited a discrepancy between CD1a vs. CD1b and c expression [15]. They also took up mannosylated ligands through a specific receptor [20,47,48]. Therefore, like their cord-blood precursor homologs, these monocyte-derived DC are probably related to interstitial DC potentially located in the dermis as immature sentinels ready for antigen capture.…”

Section: Discussionmentioning

confidence: 99%

Monocyte-derived dendritic cells have a phenotype comparable to that of dermal dendritic cells and display ultrastructural granules distinct from Birbeck granules

Grassi

Dezutter‐Dambuyant

McIlroy

et al. 1998

Journal of Leukocyte Biology

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Most monocyte-derived dendritic cells (DC) display CD1a, like Langerhans cells (LC) and some dermal DC, but their relationship with these skin DC remains unclear. To address this issue, we studied the expression of different antigens characteristic of skin DC and of monocyte/macrophages in CD1a ؉ and CD1a ؊ monocyte-derived DC. Their phenotype indicated that they may be related to dermal DC rather than to LC, i.e., they were all CD11b-positive, and 72% were Factor XIIIapositive, but they did not express E-cadherin nor VLA-6. It is interesting that CD1a ؉ and CD1a

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“…Myeloid DC differentiate from CD34 ϩ hematopoietic progenitor cells and can develop into two recognized subsets, Langerhans cells (LC), which are mostly found in the epidermis, and interstitial DC (IDC), which are mostly located in connective tissues (4,5). Because of their critical role in orchestrating the immune response, DC have been used as a cellular adjuvant in immunotherapy of cancer.…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

Inducing Antitumor T Cell Immunity: Comparative Functional Analysis of Interstitial Versus Langerhans Dendritic Cells in a Human Cell Line Model

Santegoets

Bontkes²,

Stam³

et al. 2008

The Journal of Immunology

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Dendritic cells (DC) are increasingly applied as a cellular adjuvant in immunotherapy of cancer. Two major myeloid DC subsets are recognized: interstitial DC (IDC) that infiltrate connective tissues and Langerhans cells (LC) that line epithelial surfaces. Yet, functional differences between IDC and LC remain to be defined. We recently showed that the CD34+ acute myeloid leukemia cell line MUTZ-3 supports differentiation of both DC-SIGN+ IDC and Langerin-positive Birbeck granule-expressing LC. By comparative functional characterization of MUTZ-3 IDC and MUTZ-3 LC, we aimed to elucidate the relative abilities of these two DC subsets to induce a specific T cell response and reveal the more suitable candidate for use as a clinical vehicle of tumor vaccines. Although mature LC and IDC displayed comparable lymph node-homing potential, mature LC showed higher allogeneic T cell stimulatory capacity. Nevertheless, IDC supported the induction of tumor Ag-specific CD8+ T cells at an overall higher efficiency. This might be related to the observed inability of LC to release T cell stimulatory cytokines such as IL-12p70, IL-23, and IL-15. Although this inability did not result in a detectable deviation in the cytokine expression profile of primed T cells, transduction with IL-12p70 significantly improved priming efficiency of LC, and ensured a functional equivalence with IDC in this regard. In conclusion, except for the inability of LC to release distinct type 1 T cell stimulatory cytokines, in vitro function of LC and IDC suggests comparable abilities of both subsets for the in vivo induction of antitumor T cells.

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CD34+ Hematopoietic Progenitors from Human Cord Blood Differentiate Along two Independent Dendritic Cell Pathways in Response to GM-CSF+TNFα

Cited by 166 publications

References 28 publications

Mesenchymal Stem Cells Inhibit Generation and Function of Both CD34+-Derived and Monocyte-Derived Dendritic Cells

Mesenchymal Stem Cells Inhibit Generation and Function of Both CD34+-Derived and Monocyte-Derived Dendritic Cells

Monocyte-derived dendritic cells have a phenotype comparable to that of dermal dendritic cells and display ultrastructural granules distinct from Birbeck granules

Inducing Antitumor T Cell Immunity: Comparative Functional Analysis of Interstitial Versus Langerhans Dendritic Cells in a Human Cell Line Model

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