Dendritic cell ontogeny: A human dendritic cell lineage of myeloid origin

Olweus, Johanna; BitMansour, Andrew; Warnke, Roger A.; Thompson, P. A.; Carballido, José M.; Picker, Louis J.; Lund-Johansen, Fridtjof

doi:10.1073/pnas.94.23.12551

Cited by 421 publications

(346 citation statements)

References 49 publications

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“…For comparison, the same populations of myeloid precursor cells that can be found in normal human cord blood is also shown in Table 2. These results demonstrate the presence in these mice of the same mDC precursors that are normally isolated from human peripheral blood, cord blood, and fetal bone marrow [2, 4, 13,20,21].…”

Section: Characterization Of Human DC Progenitor Cells In the Bone Mamentioning

confidence: 69%

“…Previously, Nobuyoshi et al [12] reported human DCs present in the bone marrow of transplanted NOD/SCID mice with a CD34 -CD4 + HLA-DR + phenotype. Unfortunately, these analysis did not explore the nature of the different DC precursor/progenitor populations, and the criteria used to identify human DCs did not include analysis of CD11c or CD123 expression or analysis of expression of blood dendritic cell antigens (BDCAs) [13,14]. In this study, we address several novel aspects of human DC development in NOD/SCID mice transplanted with human CD34 + cells and demonstrate that there is a direct correlation between each of the DC progenitor and precursor populations normally found in humans and those found in transplanted mice.…”

Section: Introductionmentioning

confidence: 99%

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Development and Activation of Human Dendritic Cells In Vivo in a Xenograft Model of Human Hematopoiesis

et al. 2005

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Dendritic cells (DCs) are derived from CD34 + progenitors and play a central role in the development of immune responses and in tolerance. Their therapeutic potential underscores the need for in vivo models that accurately recapitulate human DC development and function to provide a better understanding of DC biology in health and disease. Using nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice transplanted with human CD34 + cells as a model of human hematopoiesis, we examined DC ontogeny. Progenitors of both myeloid (m) and plasmacytoid (p) DCs were identified in the bone marrow of mice up to 24 weeks after transplant, indicating ongoing and sustained production of DCs after initial engraftment. To determine whether human DCs derived from transplanted stem cells were functional, their response to acute inflammation using lipopolysaccharide (LPS) was examined. Eighteen hours after LPS administration, a dramatic increase in the plasma levels of the human inflammatory cytokines interleukin (IL)-8, IL-10, tumor necrosis factor-α, and IL-12p70 was observed. Only mDCs and not pDCs responded in vivo to LPS by upregulating CD86 and CD83. In vivo activation of human mDCs resulted in a substantial increase in the ability of mDCs to induce the proliferation of naive human T cells. Taken together, these data indicate that human CD34 + cells seem to have differentiated appropriately within the NOD/SCID microenvironment into DCs that are developmentally, phenotypically, and functionally similar to the DC subsets found in humans. Stem Cells 2005;23:264-278

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Section: Characterization Of Human DC Progenitor Cells In the Bone Mamentioning

confidence: 69%

Section: Introductionmentioning

confidence: 99%

Development and Activation of Human Dendritic Cells In Vivo in a Xenograft Model of Human Hematopoiesis

et al. 2005

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“…The predominant HLA-DR mod CD11c Ϫ DC subset (comprising 61.4% Ϯ 11.6 SD of the total DC population) was CD123 ϩ , CD4 ϩ , CD68 hi , and closely resembled in phenotype, morphology, and localization near paracortical high endothelial venules 28 the plasmacytoid tonsil DCs 17 and immature CD11c Ϫ DCs described in blood, 9,10 bone marrow, and thymus. 10 As a result, it has been suggested that this tonsil DC subset may be derived from CD11c Ϫ immature/lymphoid blood DCs. 12,17 Our study further extends the phenotype of plasmacytoid DCs and demonstrates that they express p55, CD45RB, CD24 (vib-e3), low levels of HLA-DP, but lack DC activation markers and 4-1BB ligand.…”

Section: Discussionmentioning

confidence: 99%

“…[7][8][9][10]14 Three tonsil DC subsets consisting of GCDCs, 18 plasmacytoid DCs, 17 and IDCs 16 have been described previously. Our new methodology has the advantage of avoiding potential problems of antigenic changes associated with in vitro culture 19 plus the biases induced by positive selection.…”

Section: Discussionmentioning

confidence: 99%

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Phenotypic Characterization of Five Dendritic Cell Subsets in Human Tonsils

Summers

Hock

McKenzie

et al. 2001

The American Journal of Pathology

169

121

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Dendritic cells (DCs) have a central role in the initiation and regulation of immune responses in both lymphoid and nonlymphoid tissues. They share a number of common features, notably MHC class II expression, in combination with an absence of the lineage-specific markers CD3, CD14, CD16, and CD19 (lin Ϫ ). [1][2][3] There is however considerable intra-and intertissue variation in the phenotype, morphology, function, and tissue localization of different DC populations. [1][2][3][4][5][6][7] After the identification of distinct myeloid DC and lymphoid DC subsets in mice 3 there has been increasing interest in the characterization of human DC subsets. These have been categorized on the basis of differential expression of myeloid and lymphoid lineage-associated markers, as well as their responsiveness to maturation or differentiation stimuli. 8 -13 There is evidence that myeloid DCs and lymphoid DCs direct immunogenic and tolerogenic responses, respectively. 13 It is unclear whether human DC subsets represent distinct cell lineages 10,12 or differing maturation states. 9,14 As a result, the ontogeny and interrelationship of human DC subsets requires further investigation.Tonsils have been used as a readily available source of lymphoid tissue to characterize human DCs. 15 Three tonsil DC subsets have been identified: interdigitating DCs (IDCs), 16 plasmacytoid DCs, 17 and germinal center DCs (GCDCs). 18 These DC subsets were isolated after a period of in vitro culture, which is likely to alter cell phenotype and morphology. 19 They were also positively selected from lin Ϫ cells based on their expression of the CD4, CD11c, or CD40 antigens, which would exclude any DC subsets lacking these antigens and would incorporate all DC subsets expressing those antigens into one population. The observation that both IDCs and GCDCs were heterogeneous with regard to CD11c, CD83, HLA-DR, and CD13 intensity raised the possibility that these tonsil DC populations might contain additional subsets. This is the first study to analyze the composition of tonsil DC subsets within the entire lin Ϫ HLA-DR ϩ DC population isolated using a new method that maintains the cells at 4°C to minimize changes in cellular differentiation/activation induced by the isolation procedure. We report the presence of five distinct DC subsets within human tonsils. The phenotype of each tonsil DC subset was analyzed by threecolor flow cytometry and two-color immunohistochemistry using an extensive panel of antigens relevant to DC lineage, activation state, and function. Materials and Methods Patients and SamplesAfter approval by the Canterbury Ethics Committee and appropriate informed consent, tonsils were obtained from 68 patients undergoing routine tonsillectomies, which were excised in a noninflamed state. They were trans-

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