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PubMed1983

Dendritic distribution of splenius motoneurons in the cat: comparison of motoneurons innervating different regions of the muscle.

The distribution and dendritic organization of splenius motoneurons innervating extrafusal muscle fibers in different regions of the muscle were examined by electrophysiological and intracellular HRP staining techniques. Motoneurons innervating the regions of the splenius muscle supplied by the C2, C3, and C4 peripheral nerves were arranged in three nonoverlapping subnuclei. Reconstructions of the dendritic trees of splenius motoneurons in these three subnuclei showed that there were no major differences in their dendritic distributions. Instead, the dendritic distribution followed a single pattern which was composed of five major dendritic projections. These included a dorsolateral projection to the lateral part of lamina VIII, a lateral projection into the spinal accessory nucleus and beyond the gray-white border, ventral and ventrolateral dendrites in the lateral half of the ventromedial nucleus and the surrounding white matter, medial dendrites which projected both dorsally and ventrally, and finally a conspicuous collection of dendrites which projected rostrally and caudally from the cell body. These results indicate that the dendritic distributions of splenius motoneurons are not related to the segmental position of the motoneuron or the zone of the muscle innervated by the motoneuron. However, a comparison of the dendritic distribution of splenius motoneurons to the dendritic distribution of biventer cervicis-complexus motoneurons indicated that there are major differences in the form of their dendritic trees even though dendrites from both sets of motoneurons share the same territory. As a consequence, although these motoneurons may receive the same connections, the effect of these connections on the excitability of the motoneurons may differ.

Animals↗

PubMed1985

Light microscopic observations on cat Renshaw cells after intracellular staining with horseradish peroxidase. II. The cell bodies and dendrites.

The cell bodies and dendritic trees of five lumbosacral Renshaw cells of adult cats were studied in the light microscope (LM) after intracellular injection with horseradish peroxidase (HRP). The cell bodies were all located in the ventral part of lamina VII. The dendrites extended up to 0.7 mm from the cell body into the neighbouring parts of laminae VIII and IX as well as into more dorsal parts of lamina VII. The dendritic branching was sparse and about half the dendrites were unbranched. The mean diameter of the cell body was positively correlated to both the combined and mean diameters of the first-order dendrites. Between four and eight dendrites originated from the cell bodies. The number of dendritic end-branches, the combined dendritic length, the mean dendritic length from the cell body to the termination of the end branches, the distance from the cell body to the termination of the most remote end-branch, the dendritic surface area, and the dendritic volume all correlated positively with the diameter of the parent first-order dendrite. The dendritic tapering was somewhat more pronounced in the Renshaw cells than previously observed in alpha- and gamma-motoneurons. The present data are discussed in relation to previous morphological observations on Renshaw cells and alpha- and gamma-motoneurons.

Animals↗

PubMed1993

A quantitative dendritic analysis of Wernicke's area in humans. I. Lifespan changes.

Age-related increases and decreases have been described in cortical dendritic neuropil. Here, we examine age-related changes in the basilar dendrites of supragranular pyramidal cells in human superior temporal gyrus (i.e., Wernicke's area) of left and right hemispheres. Tissue was obtained from 20 neurologically normal right-handers from 18-79 years: 10 males (Mage = 52.2 years; SDage = 17.4) and 10 females (Mage = 47.8; SDage = 20.5). In tissue prepared by a modified rapid Golgi technique, ten pyramidal cells were sampled from each hemisphere and evaluated according to the following parameters: total dendritic length, mean dendritic length, and dendritic segment count. Despite considerable interindividual variation, the data exhibited significant dendritic degeneration with aging. There was an age-related decrease in total dendritic length (r[20] = -0.44; P < 0.05) and especially in mean dendritic length (r[20] = -0.69; P < 0.001) with increasing age. Age-mean dendritic length correlations were negative for all segment orders and revealed a progressive decrease in segment length in more distal branches. The number of dendritic segments remained relatively stable across the age span sampled. The data also indicated that interhemispheric dendritic asymmetries decreased with age. Individuals under 50 years of age had significantly greater total dendritic length values in the left hemisphere. Interhemispheric dendritic differences were not significant in individuals over 50.

Adolescent↗

PubMed2005

Synaptic integration in dendritic trees.

Most neurons have elaborate dendritic trees that receive tens of thousands of synaptic inputs. Because postsynaptic responses to individual synaptic events are usually small and transient, the integration of many synaptic responses is needed to depolarize most neurons to action potential threshold. Over the past decade, advances in electrical and optical recording techniques have led to new insights into how synaptic responses propagate and interact within dendritic trees. In addition to their passive electrical and morphological properties, dendrites express active conductances that shape individual synaptic responses and influence synaptic integration locally within dendrites. Dendritic voltage-gated Na(+) and Ca(2+) channels support action potential backpropagation into the dendritic tree and local initiation of dendritic spikes, whereas K(+) conductances act to dampen dendritic excitability. While all dendrites investigated to date express active conductances, different neuronal types show specific patterns of dendritic channel expression leading to cell-specific differences in the way synaptic responses are integrated within dendritic trees. This review explores the way active and passive dendritic properties shape synaptic responses in the dendrites of central neurons, and emphasizes their role in synaptic integration.

Action Potentials↗

PubMed1993

Dendritic reorganization of an identified neuron during metamorphosis of the moth Manduca sexta: the influence of interactions with the periphery.

During metamorphosis of the moth, Manduca sexta, an identified leg motor neuron, the femoral extensor motor neuron (FeExt MN) undergoes dramatic reorganization. Larval dendrites occupy two distinct regions of neuropil, one in the lateral leg neuropil and a second in dorsomedial neuropil. Adult dendrites occupy a greater volume of lateral leg neuropil but do not extend to the dorsomedial region of the ganglion. The adult dendritic morphology is acquired by extreme dendritic regression followed by extensive dendritic growth. Towards the end of larval life, MN dendrites begin to regress, but the most dramatic loss of dendrites occurs in the 3 days following pupation, such that only a few sparse dendrites are retained in the lateral region of leg neuropil. Extensive dendritic growth occurs over the subsequent days such that the MN acquires an adult-like morphology between 12 and 14 days after pupation. This basic process of dendritic remodeling is not dependent upon the presence of the adult leg, suggesting that neither contact with the new target muscle nor inputs from new leg sensory neurons are necessary for triggering dendritic changes. The final distribution of MN dendrites in the adult, however, is altered when the adult leg is absent, suggesting that cues from the adult leg are involved in directing or shaping the growth of MN dendrites to specific regions of neuropil.

Animals↗

PubMed1997

On the presence of dendrite bundles in the cerebral cortex of the Madagascan lesser hedgehog tenrec and the red-eared pond turtle.

In mammals with a well-differentiated neocortex apical dendrites of pyramidal cells form vertical bundles. Little is known about the presence of dendrite bundles in animals with a poorly differentiated cortex. In this paper the presence of dendrite bundles has been investigated in the lesser hedgehog tenrec, Echinops telfairi, a basal insectivore with a very low degree of neocorticalization. In a further step the arrangement of dendrites has been analyzed in the cerebral cortex of the red-eared pond turtle, Pseudemys scripta elegans. Among non-mammalian vertebrates, reptiles have a cerebral cortex that is relatively most comparable with the mammalian one, and the cerebral cortex of turtles shows more structural and functional similarities with the cortex in mammals than those of other reptiles. In the hedgehog tenrec, bundles of apical dendrites are found in all neo-cortical areas, the cingulate and retrosplenial cortices. The shape and arrangement of dendrite bundles are primarily determined by apical dendrites of lamina V pyramids. Apical dendrites originating in laminae III/IV or VI join these bundles, and do not give rise to separate sets of bundles in the supra- and infragranular layers as in other mammals. Center to center distances between bundles determined in the neocortical areas A(2-4) range from 7 to 76 microm, with an average of 32 microm. Area-specific differences are found concerning the length of bundles as well as the number, caliber, branching pattern and packing density of dendrites sharing an individual bundle. In the three-layered entorhinal cortex and the hippocampus dendrite bundles are not observed. In the turtle, no vertical bundles of dendrites are seen either in the medial, dorsomedial or medial part of the dorsal cortex. Only in the lateral part of the dorsal cortex are isolated bundles of apical dendrites originating from groups of perikarya situated below the main level of lamina II detected. Our findings suggest that the presence of dendrite bundles is closely related with the multilayered nature of the mammalian neocortex.

Animals↗

PubMed1978

Evidence for loss of Purkinje cell dendrites during late development: a morphometric Golgi analysis in the mouse.

The late postnatal development of the Purkinje cell dendritic tree in mouse cerebellar vermis was investigated in Golgi preparations by morphometric techniques in order to determine at what age adult characteristics of the Purkinje cell are achieved in the rodent brain which grows continuously throughout adult life. B6D2F1 hybrid mice were sacrificed at 9, 15, 20, 35 and 250 days of age. "Hind-brain" weights (by direct weighing) and vermis volume (determined histometrically from Golgi sections), both increased rapidly from 9 to 20 days of age and continued to increase steadily with advancing age. The growth of Purkinje dendritic field areas, determined by planimetric measurements from Golgi sections paralleled the growth curves for vermis cross-sectional area, vermis volume and "hindbrain" weight. However, stereological determinations revealed an unexpected disparity between the growth of the Purkinje dendritic field areas and changes in the total length of dendrites of Purkinje cells. The total dendritic branch length per Purkinje cell increased sharply up to 20 days of age but thereafter declined with advancing age. Dendritic spine counts on Purkinje cells revealed no change in the number of dendritic spines per unit length of dendrites between 20 and 250 days of age, however, since the Purkinje cell total branch length declined-calculations suggest that the total number of spines per cell declined after 20 days of age. Thus, the size of the cerebellum and the Purkinje cell dendritic tree continued to enlarge during late postnatal development; however, the total dendritic surface area and the total number of dendritic spines on each Purkinje cell, after reaching a peak at 20 days of age, declined with advancing age. The data suggest that the late postnatal development of the Purkinje cell dendritic tree is characterized by resorption as well as dendritic growth. The functional significance of such developmental remodelling is unknown.

Age Factors↗

PubMed1986

Dendritic development in the rat superior cervical ganglion.

Previous studies from our laboratory have shown that synaptogenesis in the superior cervical sympathetic ganglion (SCG) of the rat occurs predominantly during the first weeks after birth. The purpose of the present study was to examine the normal development of dendrites of the ganglion neurons, and to assess the importance of the afferent input in shaping this development. Two independent methods for examining dendritic morphology were used. One was to label neurons in the SCG by injecting a conjugate of horseradish peroxidase and wheat germ agglutinin (HRP-WGA) into a target of the SCG neurons (the submandibular gland). This procedure results in a 'Golgi-like' filling of the retrogradely labelled cell bodies and their dendrites. The second method was stereologic analysis (point-counting) of electron micrographs of sections of the SCG. At birth, the ganglion neurons give rise to an average of 2.4 primary dendrites and 1.2 secondary branches. No tertiary branches are observed at this age. The total dendritic length is 15.3 microns. Electron microscopic stereology reveals that the mean volume occupied by dendrites in the newborn SCG is 0.0093 mm3. In the adult, there is an average of 5.2 primary, 6.3 secondary, 4.8 tertiary and 1.9 quaternary dendrites. The total dendritic length is increased 23-fold to 347 microns. The mean volume occupied by dendrites is 0.0771 mm3, representing an 8-fold increase. In ganglia from adult rats which were deafferented at birth, an essentially normal dendritic form is attained. There are 4.5 primary, 6.2 secondary, 2.8 tertiary and 2.2 quaternary dendrites, and the total dendritic length is 297 microns. The mean volume of dendrites is 0.0571 micron3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Age-dependent changes in the capacity of rat sympathetic neurons to form dendrites in tissue culture.

We compared the ability of prenatal and postnatal rat sympathetic neurons to form dendrites in tissue culture. Dendrites were distinguished from axons by light microscopic criteria after intracellular dye injection and by differential immunostaining with antibodies to microtubule-associated protein-2 and to both non-phosphorylated and phosphorylated forms of the M and H neurofilament subunits. When maintained in the absence of serum and non-neuronal cells, most (72%) prenatal neurons were unipolar and had only an axon. In contrast, most (89%) neurons derived from postnatal ganglia were multipolar and extended both axons and dendrites. The dendritic morphology of postnatal neurons was usually simple with cells commonly having 2-5 short (50-200 microns), relatively unbranched dendrites. Thus, as the development of the dendritic arbor progresses in situ, sympathetic neurons acquire an enhanced ability to extend dendrites in tissue culture. To determine whether changes in the capacity to develop dendrites might occur with aging in vitro, ganglia were removed from prenatal rats and grown as explants for 3 weeks in the presence of non-neuronal cells; under these conditions, prenatal neurons within the explant became multipolar. When neurons derived from aged explants were subsequently maintained in dissociated cell culture, most formed dendrites. In cultures treated with an antimitotic agent, neurons typically had 1-4 unbranched dendrites; greater amounts of dendritic growth occurred in cultures in which ganglionic non-neuronal cells were allowed to proliferate. We conclude that: (1) the acquisition of the capacity to form dendrites in dissociated cell culture does not require either normal afferent input or physical contact with the target tissue; and (2) even after aging in vitro, sympathetic neurons remain responsive to the dendrite-promoting activity of ganglionic non-neuronal cells.

Adrenergic Fibers↗

PubMed2006

Dendritic cells in patients with type I Gaucher disease are decreased in number but functionally normal.

Gaucher disease is a lysosomal storage disorder, in which undigested glucosylceramide is deposited in the cytoplasm of mature macrophages, which accumulate in the bone marrow and the reticuloendothelial system. Dendritic cells are bone marrow-derived cells, specialized for the uptake, processing, transport and presentation of antigens to T-lymphocytes. We investigated peripheral blood dendritic cell-precursors, as well as the potential of peripheral blood monocytes and bone marrow-derived progenitor cells, to differentiate into mature dendritic cells in 12 patients with type I Gaucher disease. Results of the 10 adult patients were compared with those of 10 healthy volunteers, matched for age and sex. Six patients were anemic and 9 were thrombocytopenic, but none had severe bone disease. Both myeloid and plasmacytoid dendritic cells of patients with Gaucher disease, as well as the yield of the monocyte-derived dendritic cells, obtained after GM-CSF and IL-4 stimulation, were found significantly decreased, when compared to controls (myeloid dendritic cells: 0.19 +/- 0.07% vs. 0.34 +/- 0.10%, P = 0.009, plasmacytoid dendritic cells: 0.17 +/- 0.12% vs. 0.39 +/- 0.13%, P = 0.004, monocyte-derived dendritic cells: 4.8 +/- 3.5% vs. 8.3 +/- 3.2%, P = 0.036). However, the immunophenotypic profile of dendritic cells, estimated by CD1a, CD40, CD54, CD80, CD83 and HLA-DR expression, the endocytic and allo-stimulatory capacity of the immature, as well as of the TNF-alpha- or lipopolysaccharite-stimulated mature monocyte-derived dendritic cells, was similar to those obtained by healthy controls. In addition, bone marrow-derived CD34+ cells differentiated in the presence of GM-CSF, SCF, TNF-alpha and IL-4 into mature dendritic cells that did not differ in number, phenotype and allo-stimulatory activity from those of controls. Our findings suggest that patients with Gaucher disease exhibit mainly quantitative defects of their dendritic cells' system, demonstrated by decreased circulating dendritic cell precursors of both myeloid and plasmacytoid type. This finding may contribute to the poor immune response against infectious agents and an impaired immune surveillance, associated with an increased risk of developing a neoplastic disease.

Adolescent↗

PubMed2005

Polarized secretory trafficking directs cargo for asymmetric dendrite growth and morphogenesis.

Proper growth of dendrites is critical to the formation of neuronal circuits, but the cellular machinery that directs the addition of membrane components to generate dendritic architecture remains obscure. Here, we demonstrate that post-Golgi membrane trafficking is polarized toward longer dendrites of hippocampal pyramidal neurons in vitro and toward apical dendrites in vivo. Small Golgi outposts partition selectively into longer dendrites and are excluded from axons. In dendrites, Golgi outposts concentrate at branchpoints where they engage in post-Golgi trafficking. Within the cell body, the Golgi apparatus orients toward the longest dendrite, and this Golgi polarity precedes asymmetric dendrite growth. Manipulations that selectively block post-Golgi trafficking halt dendrite growth in developing neurons and cause a shrinkage of dendrites in mature pyramidal neurons. Further, disruption of Golgi polarity produces neurons with symmetric dendritic arbors lacking a single longest principal dendrite. These results define a novel polarized organization of neuronal secretory trafficking and demonstrate a mechanistic link between directed membrane trafficking and asymmetric dendrite growth.

Animals↗

PubMed2005

Exercise-induced changes in dendritic structure and complexity in the adult hippocampal dentate gyrus.

Neurogenesis is a constitutive activity in the adult dentate gyrus whereby new cells are created in the subgranular zone, before becoming neurons in the dentate gyrus granule cell layer. New granule cells are thought to migrate from the subgranular zone outwards to the edge of the cell layer as they mature. In these experiments we examined the dendritic morphology of granule cells in the subgranular zone, and the inner and outer regions of the granule cell zone in Sprague-Dawley rats with low and high rates of neurogenesis. In animals with lower rates of neurogenesis, the number of primary dendrites, degree of dendritic complexity and total dendritic length was lowest in cells located in the subgranular zone, higher in inner granule cell zone neurons, and highest in outer granule cell zone granule cells. Subgranular zone granule cells typically extended one primary dendrite and had a simple, immature dendritic tree, while granule cells in the outer granule cell zone had an increased number of primary dendrites, greater dendritic complexity, and greater total dendritic length. Animals that engaged in voluntary exercise showed increased neurogenesis, and the proportion of cells with one or two primary dendrites was increased in all of the granule cell zones. Despite having fewer primary processes, these cells showed enhanced dendritic complexity and an overall increase in their total dendritic length. These results indicate that granule cell dendritic morphology may be indicative of the age and position of a cell in the granule cell layer, but that in animals with increased rates of neurogenesis, the proportion of cells exhibiting what is considered an immature phenotype is increased throughout the all regions of the dentate gyrus cell layer.

Animals↗

PubMed1984

Dendritic alteration of spinal motoneurons after ablation of somatomotor cortex.

After peripheral axotomy, mammalian spinal motoneuron dendrites have been shown to cyclically degenerate and regenerate and after spinal dorsal horn mince to initially increase in length and then atrophy with time. In our experiment the dendritic profile of rat lamina IX motoneurons in the spinal segment under the T2 vertebra was studied for 90 postoperative days after bilateral somatomotor cortex ablation. The spinal cords were impregnated by the tungstate modification of the Golgi technique. Individual lengths along dendritic segments between branching points were measured from coded slides, the data computerized, and the dendrites reconstructed by computer. Interanimal statistical comparisons were made a priori (ANOVA) and a posteriori (Neuman-Keuls). There were no statistical differences in dendritic length or in the number of dendritic segments with DPO. However, there were shifts in the internal branching of all dendrites. The lack of statistical significance between control and experimental animals in numbers of dendritic branches with shifting internal dendritic branching was evidence that the motoneuron dendrites were actively growing but internal dendritic branch losses and gains were indistinguishable and approximately equally along the dendrite. These shifts in internal dendritic branching may be due to loss of information from the descending tracts.

Animals↗

PubMed1988

Selective localization of messenger RNA for cytoskeletal protein MAP2 in dendrites.

For nerve cells to develop their highly polarized form, appropriate structural molecules must be targeted to either axons or dendrites. This could be achieved by the synthesis of structural proteins in the cell body and their sorting to either axons or dendrites by specific transport mechanisms. For dendrites, an alternative possibility is that proteins could be synthesized locally in the dendritic cytoplasm. This is an attractive idea because it would allow regulation of the production of structural molecules in response to local demand during dendritic development. The feasibility of dendritic protein synthesis is suggested both by the existence of dendritic polyribosomes and by the recent demonstration that newly synthesized RNA is transported into the dendrites of neurons differentiating in culture. However, to date there has been no demonstration of the selective synthesis of an identified dendrite-specific protein in the dendritic cytoplasm. Here, we use in situ hybridization with specific complementary DNA probes to show that messenger RNA for the dendrite-specific microtubule-associated protein MAP2 (refs 3-5) is present in dendrites in the developing brain. By contrast the mRNA for tubulin, a protein present in both axons and dendrites is located exclusively in neuronal cell bodies.

Animals↗

PubMed2002

Expression and function of the mannose receptor CD206 on epidermal dendritic cells in inflammatory skin diseases.

The capability to take up mannosylated protein antigens is important for the biologic function of dendritic cells, as many glycoproteins derived from bacteria and fungi, e.g., Malassezia furfur, are mannosylated. The expression of the mannose receptor CD206 has been regarded a differentiation hallmark of immature dendritic cells, whereas monocytes and mature dendritic cells as well as epidermal Langerhans cells do not express CD206. This study describes some epidermal dendritic cells that may express CD206 under inflammatory skin conditions: Immunohistochemical and flow cytometric analysis with the CD206-specific D547 antibody confirmed that Langerhans cells from normal human skin do not express CD206. Epidermal cell suspensions from atopic dermatitis and psoriasis revealed two distinct subsets of epidermal dendritic cells: a CD1a(+++)/CD206(-) cell population (i.e., Langerhans cells) and a CD1a(+)/CD206(++) cell population, corresponding to the previously described inflammatory dendritic epidermal cells. CD206-mediated endocytosis, assessed by dextran-fluorescein isothiocyanate uptake, was demonstrated in inflammatory dendritic epidermal cells but not in Langerhans cells. CD206-independent uptake of the fluorescent dye Lucifer yellow, a pinocytosis marker, was demonstrated in both Langerhans cells and inflammatory dendritic epidermal cells. Electron microscopic examination, known to distinguish Langerhans cells from inflammatory dendritic epidermal cells by their Birbeck granules, revealed Langerhans cells with Birbeck granules and inflammatory dendritic epidermal cells without Birbeck granules. Inflammatory dendritic epidermal cells exhibited numerous coated pits and vesicles, the latter fusing with large endosome-like structures, thus suggesting a high endocytotic activity. Immunogold staining with D547 monoclonal antibody confirmed that inflammatory dendritic epidermal cells were positive for CD206. In conclusion, inflammatory dendritic epidermal cells but not Langerhans cells are expressing CD206 in situ and use it for receptor-mediated endocytosis.

Cell Differentiation↗

PubMed1998

Increased nitric oxide (NO) production by antigen-presenting dendritic cells is responsible for low allogeneic mixed leucocyte reaction (MLR) in primary biliary cirrhosis (PBC).

The levels of blastogenesis in allogeneic MLR containing T cells from one normal volunteer and irradiated dendritic cells from 29 patients with PBC, 17 patients with chronic hepatitis type C (CH-C) and 22 allogeneic normal controls were compared to see if there is any role of antigen-presenting cells (APC) in the pathogenesis of PBC. The stimulatory capacity of dendritic cells from PBC was significantly lower compared with that of dendritic cells from CH-C (P < 0.05) and normal controls (P < 0.05), which could not be attributable either to the levels of expression of surface molecules, such as HLA-DR and CD86 on dendritic cells, or to the levels of cytokines, such as IL-10 and IL-12. Significantly higher levels of NO were seen in the allogeneic MLR supernatants containing dendritic cells from PBC compared with the supernatants from cultures containing dendritic cells from CH-C (P < 0.001) or normal controls (P < 0.001). Moreover, dendritic cells from PBC produced 10 times more NO compared with dendritic cells from CH-C and normal controls (21.9 +/- 2.8 microM versus 1.6 +/- 0.3 microM and 1.6 +/- 0.3 microM, respectively; P < 0.001). The addition of N(G)-monomethyl-L-arginine monoacetate (L-NMMA), a known inhibitor of NO in allogeneic MLR containing dendritic cells from PBC, resulted in a significant decrease of NO and increase of blastogenesis. The selective impairment of dendritic cell function, increased production of NO by dendritic cells and restoration of blastogenesis using NO inhibitor in PBC have suggested a role for NO and dysfunction of dendritic cells in the pathogenesis of PBC. This inspires optimism that modulating the function of dendritic cells and controlling NO production, an improved therapeutic approach, might be planned for PBC.

Adult↗

PubMed2002

Interleukin-10-treated dendritic cells modulate immune responses of naive and sensitized T cells in vivo.

Interleukin-10 is a pleiotropic cytokine known to have inhibitory effects on the accessory functions of dendritic cells. In vitro, interleukin-10 converts immature dendritic cells into tolerizing antigen- presenting cells. To assess whether interleukin-10-treated dendritic cells exert tolerizing effects in vivo, CD4+ T cells from DO11.10 ovalbumin-T cell receptor transgenic mice were transferred to syngeneic BALB/c recipients. Recipient animals were treated with ovalbumin-pulsed/unpulsed, interleukin-10-treated/untreated CD11c+ dendritic cells thereafter and ovalbumin-specific proliferation of lymph node cells was assessed by restimulation with the peptide in vitro. In prophylactic experiments, recipients received naive CD4+ DO11.10 T cells and were immunized with ovalbumin323-339 peptide in incomplete Freund's adjuvant after treatment with various subtypes of dendritic cells. Strong ovalbumin-specific proliferation was observed in animals immunized with control ovalbumin-dendritic cells. Minimal proliferation was found in mice treated with ovalbumin-pulsed, interleukin-10-treated dendritic cells. In therapeutic experiments, preactivated CD4+ DO11.10 T cells were transferred, and recipients were treated with dendritic cells as described. Ovalbumin-specific proliferation was strong in recipients treated with ovalbumin-dendritic cells. CD4+ T cell proliferation from ovalbumin-interleukin-10-dendritic cell treated animals was below background. When delayed type hypersensitivity reactions in the footpads of prophylactically or therapeutically vaccinated animals were tested, mice treated with ovalbumin-interleukin-10-dendritic cells showed no footpad swelling compared with controls. Rechallenge with the antigen in vitro and in vivo did not alter the inhibitory effect of interleukin-10-treated dendritic cells. Thus, interleukin-10-treated dendritic cells inhibit ovalbumin-specific immune responses in naive and sensitized mice.

Animals↗

PubMed2001

Two subsets of dendritic cells are present in human cerebrospinal fluid.

Little is known about the presence of dendritic cells in the human CNS. To investigate the occurrence of dendritic cells in the CSF, paired blood/CSF samples from patients with multiple sclerosis, acute optic neuritis, Lyme neuroborreliosis, other inflammatory neurological diseases and non-inflammatory neurological diseases were examined using flow cytometry. Almost all CSF samples contained myeloid (lin-CD11c+HLA-DR++CD123(dim)) and plasmacytoid (lin-CD11c-HLA-DR+CD123(high)) dendritic cells. In non-inflammatory neurological diseases, dendritic cells of either subset only constituted up to 1% of CSF mononuclear cells. Myeloid CSF dendritic cells were elevated in optic neuritis, neuroborreliosis and other inflammatory neurological disorders, while plasmacytoid dendritic cells were elevated in all neuroinflammatory conditions studied, with especially high numbers in neuroborreliosis. Numbers of CSF dendritic cells correlated with the common parameters of CNS inflammation. The myeloid dendritic cells in CSF expressed higher levels of HLA-DR, CD86, CD80 and CD40 than those in blood, whereas expression of these molecules by plasmacytoid dendritic cells was equal in blood and CSF. Both CSF and blood dendritic cells expressed the chemokine receptor CCR5. This is the first demonstration that dendritic cells are present in human CSF and that plasmacytoid dendritic cells are present in a non-lymphoid compartment. Myeloid and plasmacytoid dendritic cells in CSF may contribute to orchestration of the local immune responses.

Adult↗