Identification of hematopoietic progenitors of macrophages and dendritic Langerhans cells (DL-CFU) in human bone marrow and peripheral blood

Reid, C. D. L.; Fryer, P.; Clifford, Caroline; Kirk, Ann; Tikerpae, J.; Knight, Stella C.

doi:10.1182/blood.v76.6.1139.1139

Cited by 162 publications

(1 citation statement)

References 18 publications

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“…DC from lymphoid tissues are non-replicating and originate from a bone marrow proliferating precursor (reviewed by Bowers and Goodell in reference [112]). Very little is known about DC precursors except that they are Ia~ and are present in cultures of rat bone marrow [113] and, possibly, in human bone marrow and blood [114]. Recently, Inaba and colleagues [86] succeeded in characterising a proliferating la-negative DC precursor found in mouse blood.…”

Section: Migration Via the Bloodmentioning

confidence: 99%

Phagocytosis of Antigens by Langerhans Cells

Sousa

Austyn

1993

Advances in Experimental Medicine and Biology

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Mature dendritic cells (DC) isolated from lymphoid tissues initiate antigen-specific Tdependent responses even though they are non-phagocytic and weakly pinocytic, whereas Langerhans cells (LC; immature DC) can process protein antigens but are poorly immunostimulatory. Thus antigens may be acquired by cells of this lineage at an immature stage but, to our knowledge, there have been no studies on the phagocytic capacity of these cells in vitro.Using a newly-developed flow cytometric assay to measure the association between fluorescent markers and LC in epidermal cell cultures, and light and electron microscopy, we have observed phagocytosis of a variety of particles by freshly-isolated LC. The cells readily phagocytosed zymosan, heat-killed S. cerevisiae, bacteria (5. aureus and C . parvuni) and fluorescent latex beads, but were unable to take up IgGor complementcoated sheep erythrocytes, as opposed to M0. Similarly, many freshly-isolated splenic DC had some phagocytic activity. However, the capacity of both LC and splenic DC to phagocytose zymosan, bacteria and fluorescent latex beads was markedly decreased after maturation in culture, consistently with the fact that mature DC are poorly phagocytic.Zymosan binding and uptake were much greater in fresh LC from C57BL/6 compared to B ALB/c mice, and the loss of phagocytic capacity for zymosan during maturation followed different kinetics in the two strains. Two receptors mediating uptake of zymosan in LC were identified based on the effect of different inhibitors. Both of these receptors, recognising mannose and (3-glucan residues, appear to be differentially regulated in the two mouse strains and during culture of LC.Our findings support the notion that DC are capable of acquiring paniculate antigens for presentation at an immature stage, through recognition units for carbohydrate determinants common to a variety of potentially pathogenic organisms. ACKNOWLEDGEMENT SI would like to thank my supervisor, Dr. Jonathan Austyn, for his advice, support and friendship over the last three years and for initially showing me the heavenly light of dendrocytology while carefully concealing the infernal glow of DC purification. I thank Prof. P. J. Morris for giving me the opportunity to work in the Nuffield Department of Surgery and for financial support for some of the meetings I attended. I am extremely grateful to Prof. P. D. Stahl of the

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Section: Migration Via the Bloodmentioning

confidence: 99%

Phagocytosis of Antigens by Langerhans Cells

Sousa

Austyn

1993

Advances in Experimental Medicine and Biology

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Pulsing of dendritic cells with cell lysates from either B16 melanoma or MCA-106 fibrosarcoma yields equally effective vaccines against B16 tumors in mice

et al. 1998

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Background and Objectives: Dendritic cells (DC) pulsed in vitro with a variety of antigens have proved effective in producing specific antitumor effects in vivo. Experimental evidence from other laboratories has confirmed that shared antigens can be encountered in histologically distinct tumors. In our experiments, we set out to evaluate the immunotherapeutic potential of vaccines consisting of DC pulsed with MCA‐106 fibrosarcoma or B16 melanoma cell lysates and to determine whether a cross‐reactivity exists between the two tumors. Methods DC were prepared from the bone marrow of C57BL/6 (B6) mice by culturing progenitor cells in murine granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). They were separated into three equal groups and were either pulsed with B16 melanoma cell lysates (BDC), pulsed with tumor extract from the syngeneic fibrosarcoma MCA‐106 (MDC), or left unpulsed (UDC). DC were then used to immunize three groups of mice, with all mice receiving two weekly intravenous (IV) doses of 1 × 106 DC from their respective preparations on days −14 and −7. A fourth group of control mice were left untreated. On day 0, all mice were challenged with subcutaneous injections of 1 × 105 B16 and 1 × 105 MCA tumor cells, administered in the left and right thighs, respectively. After the inoculations, the mice were monitored closely with respect to tumor growth and survival. Results The MDC mice developed specific cellular immunity directed against not only MCA‐106 tumor cells, but also against B16 melanoma, as measured through chromium‐release assays of splenocyte preparations, while remaining ineffective at killing both L929 fibroblasts and CT26 tumor cells. By day 30 after tumor inoculations, control mice manifested the largest B16 tumor volumes at a mean of 2185 mm3, followed by the UDC, MDC, and BDC groups at 92 mm3 (P = 0.00008), 3 mm3 (P = 0.000002), and 2 mm3 (P = 0.00004), respectively. The survival data mirrored this pattern, with control animals displaying the shortest mean survival time (37.1 ± 4.0 days), followed by UDC (44.8 ± 6.6), MDC (56.2 ± 14.7), and BDC (56.4 ± 18.3) animals. No significant differences were noted between MCA‐106 and B16 cell lysate‐pulsed DC vaccines with respect to their abilities to inhibit B16 tumor growth and to prolong survival. These findings were confirmed using a B16 pulmonary metastasis model. Likewise, vaccination with interferon‐γ gene‐modified MCA‐106 tumor cells was shown to be effective at protecting against a subsequent subcutaneous B16 tumor challenge in 3 of 4 mice observed. Conclusions These results demonstrate that immunization with antigen‐pulsed DC confers cellular immunity, retards tumor growth, and prolongs the survival of tumor‐challenged mice. The ability of MCA‐106 cell lysate‐pulsed DC vaccines to inhibit the growth of subcutaneous B16 tumors also suggests the presence of shared tumor‐associated antigens between these two histologically distinct tumors. J. Surg. Oncol. 1998;68:79–91. © 1998 Wiley‐Liss, Inc.

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Human thymic dendritic cells

Lafontaine

Landry

Montplaisir

1997

Microsc. Res. Tech.

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Human thymic dendritic cells (DC) represent a member of the bone marrow–derived dendritic cell family. They have a dendritic shape and are found in small numbers mainly at the corticomedullary border and in medullary regions of the thymus. Human thymic DC were isolated by density gradient separation, followed by treatment with CD2, CD7, CD1, and CD11b mAb and immunobeads magnetic separation. The resulting population contains 60–75% brightly HLA‐DR+ cells which present the morphological characteristics of DC observed in situ. Extensive phenotypic analysis confirmed that they are of mesenchymal origin and that some express CD11a and CD54 molecules. Freshly isolated DC do not stain with a wide variety of anti‐T‐B and ‐monocyte or ‐macrophage mAb. However, they acquire the CD1 molecule after a few days in culture. By using a cell sorter we obtained 90–95% of purified human thymic DC. Functional studies have shown that human thymic DC are potent activators in mixed lymphocyte reactions, act as accessory cells in mitogenic thymocyte proliferation, increase the thymocyte proliferative response to a toxin signal, and produce IL‐1. They also formed spontaneous physical associations with thymocytes, which raises questions about the implication of DC in differentiation and/or maturation processes of thymocytes. Microsc. Res. Tech. 38:267–275, 1997. © 1997 Wiley‐Liss, Inc.

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Identification of hematopoietic progenitors of macrophages and dendritic Langerhans cells (DL-CFU) in human bone marrow and peripheral blood

Cited by 162 publications

References 18 publications

Phagocytosis of Antigens by Langerhans Cells

Phagocytosis of Antigens by Langerhans Cells

Pulsing of dendritic cells with cell lysates from either B16 melanoma or MCA-106 fibrosarcoma yields equally effective vaccines against B16 tumors in mice

Human thymic dendritic cells

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