Cultured Human Langerhans Cells Resemble Lymphoid Dendritic Cells in Phenotype and Function

Romani, Angela; Lenz, Angela; Glassel, Herta; Stössel, Hella; Stanzl, Ursula; Majdic, Otto; Fritsch, Peter; Schuler, Gerold

doi:10.1111/1523-1747.ep12319727

Cited by 349 publications

(197 citation statements)

References 46 publications

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“…Yet, it still requires maturation stimuli to further differentiate and to acquire those features that characterize the terminally mature dendritic cell (13,14): 1) no reversion back to a macrophage, 2) greatly augmented T cell-stimulatory capacity for MLR and CTL, and 3) de novo expression of markers such as CD83 or DC-LAMP (22). These features are similar to those of dendritic cells that matured spontaneously from blood after 2 days of culture (26) or of cultured epidermal Langerhans cells (27,28). Staphylococci induce more IL-12 in immature than in mature monocyte-derived dendritic cells In 11 independent experiments, IL-12 values from immature dendritic cells ranged between 2.1 and 0.02 ng/ml; values from corresponding populations of mature dendritic cells ranged from 0.5 to 0 (i.e., below detection threshold) ng/ml.…”

Section: Resultsmentioning

confidence: 95%

Production of IL-12 by Human Monocyte-Derived Dendritic Cells Is Optimal When the Stimulus Is Given at the Onset of Maturation, and Is Further Enhanced by IL-4

Ebner¹,

Ratzinger²,

Krösbacher³

et al. 2001

The Journal of Immunology

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143

104

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Dendritic cells produce IL-12 both in response to microbial stimuli and to T cells, and can thus skew T cell reactivity toward a Th1 pattern. We investigated the capacity of dendritic cells to elaborate IL-12 with special regard to their state of maturation, different maturation stimuli, and its regulation by Th1/Th2-influencing cytokines. Monocyte-derived dendritic cells were generated with GM-CSF and IL-4 for 7 days, followed by another 3 days ± monocyte-conditioned media, yielding mature (CD83+/dendritic cell-lysosome-associated membrane glycoprotein+) and immature (CD83−/dendritic cell-lysosome-associated membrane glycoprotein−) dendritic cells. These dendritic cells were stimulated for another 48 h, and IL-12 p70 was measured by ELISA. We found the following: 1) Immature dendritic cells stimulated with CD154/CD40 ligand or bacteria (both of which concurrently also induced maturation) secreted always more IL-12 than already mature dendritic cells. Mature CD154-stimulated dendritic cells still made significant levels (up to 4 ng/ml). 2) Terminally mature skin-derived dendritic cells did not make any IL-12 in response to these stimuli. 3) Appropriate maturation stimuli are required for IL-12 production: CD40 ligation and bacteria are sufficient; monocyte-conditioned media are not. 4) Unexpectedly, IL-4 markedly increased the amount of IL-12 produced by both immature and mature dendritic cells, when present during stimulation. 5) IL-10 inhibited the production of IL-12. Our results, employing a cell culture system that is now being widely used in immunotherapy, extend prior data that IL-12 is produced most abundantly by dendritic cells that are beginning to respond to maturation stimuli. Surprisingly, IL-12 is only elicited by select maturation stimuli, but can be markedly enhanced by the addition of the Th2 cytokine, IL-4.

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Section: Resultsmentioning

confidence: 95%

Production of IL-12 by Human Monocyte-Derived Dendritic Cells Is Optimal When the Stimulus Is Given at the Onset of Maturation, and Is Further Enhanced by IL-4

Ebner¹,

Ratzinger²,

Krösbacher³

et al. 2001

The Journal of Immunology

Self Cite

143

104

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“…Although the migration of DC from liver [15] or cardiac allografts [49] to T-dependent areas of recipient spleens has been studied in mice, the functional properties of these cells, or of 627 the precursors from which they are derived have only recently been described [19,21,88,90]. The best characterized DC isolated from nonlymphoid tissues are the MHC class II+ epidermal Langerhans cells (LC) [91]. When freshly isolated, these cells have a phenotype distinct from "mature" lymphoid DC and can process exogenous antigens.…”

Section: In Nonlymphoid Organsmentioning

confidence: 99%

Microchimerism, dendritic cell progenitors and transplantation tolerance

et al. 1995

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Abstract. The recent discovery of multilineage donor leukocyte microchimerism in allograft recipients up to three decades after organ transplantation implies the migration and survival of donor stem cells within the host. It has been postulated that in chimeric graft recipients, reciprocal modulation of immune responsiveness between donor and recipient leukocytes may lead, eventually, to the induction of mutual immunologic nonreactivity (tolerance). A prominent donor leukocyte, both in human organ transplant recipients and in animals, has invariably been the bone marrowderived dendritic cell (DC). These cells have been classically perceived as the most potent antigenpresenting cells but evidence also exists for their tolerogenicity. The liver, despite its comparatively heavy leukocyte content, is the whole organ that is most capable of inducing tolerance. We have observed that DC progenitors propagated from normal mouse liver in response to GM-CSF express only low levels of major histocompatibility complex (MHC) class II antigen and little or no cell surface B7 family T cell costimulatory molecules. They fail to activate resting naive allogeneic T cells. When injected into normal allogeneic recipients, these DC progenitors migrate to T -dependent areas of host lymphoid tissue, where some at least up regulate cell surface MHC class II. These donor-derived cells persist indefinitely, recapitulating the behavior pattern of donor leukocytes after the successful transplantation of all whole organs, but most dramatically after the orthotopic (replacement) engraftment of the liver.Correspondence: Dr.

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“…From these organs mature DC emigrate via the lymphoid system after antigen uptake and processing [7]. DC can be isolated from various sources using sophisticated protocols [8,9]. Due to the low cell numbers available after purification functional studies are, however, difficult to perform.…”

Section: Introductionmentioning

confidence: 99%

Morphologically and functionally intact dendritic cells can be derived from the peripheral blood of aged individuals

Steger

Maczek

Grubeck‐Loebenstein

1996

Clinical and Experimental Immunology

128

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SUMMARYDendritic cells are antigen-presenting cells (APC), which are crucial for the initiation of an immune response. In spite of the well known decline of immune function in old age, no information is yet available on whether dendritic cells are also affected by the ageing process. It was therefore the aim of this study to compare peripheral blood dendritic cells (DC) from old and young healthy individuals. Using granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4, DC were propagated from peripheral blood mononuclear cells (PBMC). The obtained cell populations had a typical dendritic morphology and expressed HLA class I and class II, CD23, CD32, CD40, CD44 and CD54, but not CD3 and CD19. Larger numbers of DC were obtained from old individuals than from young ones in spite of a similar expression pattern of surface molecules. DC from aged persons also survived better under in vitro culture conditions. When tested for their antigen-presenting capacity, DC from young and old individuals were equally effective in inducing the proliferation of tetanus toxoid-specific T cell clones after antigenic stimulation. Peripheral blood DC from aged individuals may thus still function as powerful APC. They may represent useful tools for immunotherapy in the aged.

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Cultured Human Langerhans Cells Resemble Lymphoid Dendritic Cells in Phenotype and Function

Cited by 349 publications

References 46 publications

Production of IL-12 by Human Monocyte-Derived Dendritic Cells Is Optimal When the Stimulus Is Given at the Onset of Maturation, and Is Further Enhanced by IL-4

Production of IL-12 by Human Monocyte-Derived Dendritic Cells Is Optimal When the Stimulus Is Given at the Onset of Maturation, and Is Further Enhanced by IL-4

Microchimerism, dendritic cell progenitors and transplantation tolerance

Morphologically and functionally intact dendritic cells can be derived from the peripheral blood of aged individuals

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