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C Dezutter-Dambuyant

Publications and source records attributed to C Dezutter-Dambuyant.

At least 55 records · Page 3Linked to original sources
PubMed1995

Immunophenotypic and ultrastructural evidence of the langerhans cell origin of the canine cutaneous histiocytoma.

Canine cutaneous histiocytoma (CCH), a histiocytic benign, dermal, self-healing tumor in the young dog, and epidermal Langerhans cells (LC) are thought to be related. In this study, we used immunohistochemical staining and transmission electron microscopy for 5 fresh CCH and 17 fixed tumors, to examine if, on the basis of their immunophenotype and their ultrastructural morphology, these tumor cells originate as LCs. The immunophenotype of CCH: canine CD11a, 11c, 18, 45, MHC II positive and ACM1, human CD14 negative, was different from canine macrophage immunophenotype but very similar to the canine LC phenotype. Furthermore, we have described ultrastructural markers in CCH cells for the first time: these consist of coated vesicles, regularly laminated bodies, pleiomorphic inclusions, paracrystalline structures, and deep invaginations of the plasma membrane, usually observed in congenital self-healing histiocytosis, a human LC tumor, or occasionally observed in human LC. The occurrence of such immunophenotype and ultrastructural markers confirmed the common lineage of LCs and CCH cells.

Animals↗
PubMed1995

Role of specific successive contacts between extracellular matrix proteins and epidermal Langerhans cells in the control of their directed migration.

To migrate from epidermis to regional lymph nodes, antigen-bearing epidermal Langerhans cells (LC) must move through extracellular matrix (ECM) of various composition. The present study was designed to contrast the ability of basement membrane (BM)- and dermis-ECM components to successively stimulate the adhesion of normal human epidermal LC, in vitro. For this purpose, we used highly enriched LC suspensions (70%-80%), allowed them to attach to one ECM substrate, and then studied the readhesion properties of these recovered ECM-attached LC to the same and different ECM substrates. Each of four ECM molecules (laminin (LM), fibronectin (FN), type I and type IV collagen) was tested in pairs. Readhesion of recovered LM and type IV collagen-attached cells did not affect readhesion to FN and type I collagen, indicating that the interaction of LC with the BM components can be normally followed by interaction with the dermis-ECM molecules. In contrast, readhesion of recovered FN-, type I collagen-, and type IV collagen-attached cells to LM was significantly reduced. The findings indicate that following contact to BM components, epidermal LC are able to attach to ECM proteins present in the dermis, whereas once they have made contact with ECM present in the dermis, they reduce their binding capacity to the BM laminin, suggesting the contact with the dermal components could prevent LC from reentering the epidermal compartment. Binding to LM and FN was also shown to induce a decline in the expression of CD1a, known as a specific marker restricted to epidermal LC.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, CD↗
PubMed1995

[Recent data and current studies of epidermal Langerhans cells].

The skin may be considered as well as a target and an iniator of self immune reactions. Two to 5% of the epidermal cells are Langerhans cells (LC) which are the only cells to specifically take, process and present the antigens to lymphocytes in order to induce an immune response. Such an ability and location of these cells enhance their role in antigenic stimulations and immuno-allergic reactions. TNF alpha was showed to potentiate the effect of GM-CSF for the generation of LC from their CD34+ precursors. Originated from the bone marrow, the LC colonize the epithelia where they act as antigen presenting cells by taking, processing antigens, and migrating to lymph nodes where they sensitize T cells. In vitro incubation of LC mimics their phenotypic, morphologic and functional maturation (enhanced accessory function) while they are migrating in vivo to lymph nodes where they are called interdigitating cells. Animal models might clarify such an hypothesis. Mechanisms leading to the LC immigration or the emigration from epithelia in order to play their immune functions remain obscure. Although LC are purified with difficulty and no immortalized human cell lines exist, these cells are still an ideal APC dendritic cell model. They will certainly be considered, in the next future, as the pivotal role of vaccinal strategy.

Antigens, CD34↗
PubMed1995

[Epithelial dendritic cells and HIV-1 infection in vivo and in vitro].

The skin and mucosa are the first line of defense of the organism against external agents, not only as a barrier between the body and the environment but also as the site of initiation of immune reactions. The immunocompetent epidermal cells which act as antigen-presenting cells (APC) are Langerhans cells (LC). Many indirect and/or direct experimental data have shown that LC may be a privileged target, reservoir and vector of dissemination for the human immunodeficiency virus (HIV) from the inoculation sites (mucosa?) to lymph nodes where the emigrated infected LC could infect T lymphocytes. In vitro infection confirms their permissivity to viral replication. HIV infection may modify the APC function of LC which could contribute to amplify the immunosuppressive state found in AIDS. Furthermore, mechanisms leading to the re-activation of viral expression at the cutaneous level need to be explored. An ideal animal model may readily clarify the role of LC in AIDS pathology and in transmucosal infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

[Dendritic cells in dogs and cats: models of study in human pathology].

Langerhans' cells (LC) are epidermal bone-marrow-derived dendritic cells. They represent in mankind 1 to 6% of the epidermal cells from which they can be distinguished by specific phenotype (membrane receptors and antigens related to the immune function) and by ultrastructural specific organelles: the Birbeck granules. In dogs and cats, such cells were recently described; they display a phenotype very similar to that of human LC (CD1, CD8, CD11/18, CD45 and MHC II positive for canine LC, and CD18, CD4, panleukocyte antigen and MHC II positive for feline ones) and in both species, Birbeck granules are observed. Furthermore occurs in dog a benign self-healing LC tumor: the canine cutaneous histiocytoma (CCH). This tumor exhibits numerous comparison points with a human LC disorder named Hashimoto-Pritzker disease, and thus may constitute an interesting model to explore causes of such a proliferation and mechanisms of tumor rejection. In 1986, Pedersen isolated in cats a new retrovirus very similar to the human immunodeficiency virus (HIV), the feline immunodeficiency virus (FIV). Since human LC may be infected by HIV, feline LC may represent a good candidate for an FIV model for exploring the infection of human LC by the HIV and for shedding light on the role of human LC located in the mucous membranes in the initial viral inoculation process.

Animals↗
PubMed1994

Development of motility of Langerhans cell through extracellular matrix by in vitro hapten contact.

To study the migration capacity of Langerhans cells in vitro, a reconstituted basement membrane invasion assay (Matrigel assay) was performed. Partially enriched human epidermal Langerhans cell suspensions (6-20%) were incubated with or without haptens [2,4,6-/trinitrobenzenesulfonic acid (TNBS) and fluorescein isothiocyanate (FITC)] or an irritant sodium lauryl sulfate (SLS) in Hanks' balanced salt solution for 10 min at 37 degrees C, and were then used for the invasion assay. Fibroblast-conditioned medium prepared from human dermal fibroblasts was used as a source of chemoattractants. Non-treated cells showed a gradual increase in migration of HLA-DR-positive cells through the Matrigel-coated filters in a time-dependent manner. In vitro TNBS and FITC treatment resulted in a significant stimulation of this migration. By contrast, SLS treatment did not increase the number of migrating cells. The migration capacity of hapten-treated cells decreased both in the absence of human fibroblast-conditioned medium and in the presence of this medium in the upper compartment of the chamber, indicating that this medium actually functioned as chemoattractant. Our findings suggest that the contact between hapten and Langerhans cells could be one of the triggers to initiate and/or stimulate Langerhans cell migration from the epidermis to the dermis. In addition, some factors derived from the dermal fibroblasts may promote and regulate the directional migration of Langerhans cells.

Basement Membrane↗
PubMed1994

Detection of HIV-specific DNA sequences in epidermal Langerhans cells infected in vitro by means of a cell-free system.

As dendritic antigen-presenting cells in skin and mucous membranes, Langerhans cells (LC) are found in areas at risk of inoculation by the human immunodeficiency virus (HIV). LC have been reported as targets for HIV-1. The aim of the present study was to investigate whether LC can be experimentally infected by HIV provided by a cell-free infection system. A cell-free suspensions was prepared from viral particles provided by chronically infected cell lines (U937 or H9 cells) by low-speed centrifugation followed by 0.45-microns filtration. LC-enriched epidermal cell (EC) suspensions with no CD3+ cells (assessed by flow cytometry and electron microscopy) and uninfected U937 cells (cell-free infection system control) were infected with two isolates (HTL VIII-B and RF). The infectiousness of the cell-free virus fluids was controlled on U937 cells where proviral DNA was amplified (gag, pol, and env gene sequences by the polymerase chain reaction, PCR) and release of virus particles into the supernatant was controlled either by measure of the reverse transcriptase (RT) activity or detection of viral RNA amplified by RT-PCR for the gag gene sequences). Proviral DNA (gag gene sequences) was found in LC-enriched epidermal cellular DNA from day 4 post-infection with isolate HTL VIII-B and from day 7 with isolate RF. Although the RT activity did not reach a significantly high level, viral RNA was found in the supernatant of LC-enriched EC cultures at the same time as proviral DNA was detected in LC.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1994

Epidermal and mucosal dendritic cells and HIV1 infection.

The major modes of HIV1 transmission involve circumstances and behavior that promote exchange of blood or body fluids containing HIV virus and/or HIV infected cells. In the second group, semen, vaginal secretions, exudates and occasionally saliva have been documented as sources of transmission. If the skin, protected by the horny layer, does not seem easily infected, the mucous membrane and especially the vaginal, rectal or oral mucosa are the main sites of HIV entry in absence of lesions. In mucosa, a well identified population of dendritic cells may be considered as the first target of HIV1: the Langerhans cells. Originated from the bone marrow, the Langerhans cells migrate into the peripheral epithelia (skin, mucous membranes) and play a key role in the immune surveillance system against foreign antigens. They act as antigenpresenting cells through a specific cooperation with CD4+ lymphocytes after migration to the proximal lymph nodes. As HIV1-susceptible cells, Langerhans cells in genital or rectal mucosa may be the first infected cell type and may be the vectors of infection for CD4 positive T cells. It is clearly demonstrated that LC may be infected in HIV1 seropositive patients. Recently in vitro, experimental infection of Langerhans cells was reproduced using a co-culture assay with HIV1 infected cells. Recent data obtained with transgenic mice containing HIV1 gene underline the key role of Langerhans cells in the pathogenesis process of HIV infection.

Antigen Presentation↗
PubMed1994

[Current data on epidermal Langerhans cells].

The skin may be considered as well as a target and an initiator of self immune reactions. Two to 5% of the epidermal cells are Langerhans cells which are the only cells to specifically take, process and present the antigens to lymphocytes in order to induce an immune response. Such an ability and the location of the Langerhans cells enhance the role that they may play in antigenic stimulations or immuno-allergic situations. TNF alpha was shown to potentiate the effect of GM-CSF for the generation of Langerhans cells from their CD34-positive precursors found in the cord blood. Originated from the bone marrow, the Langerhans cells colonize skin and mucosa where they act as antigen presenting cells (APC) by taking, processing antigens, and migrating to lymph nodes in order to sensitize lymphocytes. Such a migration was shown, for the first in humans, in an induced irritant contact dermatitis. In vitro incubation of isolated Langerhans cells induces morphological, phenotypical and functional modifications which make Langerhans cells similar to interdigitating cells. Such an observation suggests that in vivo Langerhans cells could undergo a maturation when they migrate to lymph nodes. Many points remain to be explored in order to clarify the conditions which may stimulate or make langerhans migrate and play their immune function. For example, cellular interactions or positive/negative effects due to soluble mediators (cytokines, neuropeptides) may modulate their role as antigen presenting cells. In vitro model of T-cell sensitization confirmed their in vivo role of cutaneous surveillance in the recognition and elimination of exogenous antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1993

Dissection of human Langerhans cells' allostimulatory function: the need for an activation step for full development of accessory function.

In the present study, we analyzed the mechanism by which human Langerhans cells (LC), the dendritic cells (DC) from epidermis, support the induction of a primary allogeneic T cell response. We reported that paraformaldehyde (PF) fixation completely abrogated the stimulatory property of freshly isolated LC, although the level of major histocompatibility complex (MHC) class II antigen (Ag) expression was unaltered by the fixative. Addition of either interleukin (IL)-1 beta and/or IL-6, during the mixed epidermal cell lymphocyte reaction, failed to restore the proliferative response. By contrast, when human LC were incubated for 3 days in culture medium before fixation, they retained a low but significant allostimulatory capacity. Trypsin treatment of incubated LC before fixation did not impair their function, suggesting that stimulatory activity by fixed incubated LC did not merely reflect a repair of LC membrane after trypsin trauma suffered during epidermal cell (EC) isolation. More interestingly, we found that addition of interferon-gamma during LC incubation mediated an enhanced allostimulatory activity by the PF-fixed LC. Acquisition of allostimulatory property by in vitro activated and fixed LC did not correlate with increased MHC class II Ag expression at the cell surface. By contrast, we showed that ICAM-1 Ag expression by human LC is involved in this maturation process. Finally, we found that once human LC have been activated, IL-1 beta, but not IL-6, could serve as a costimulatory factor in the primary allogeneic T cell response. In conclusion, the data suggest that human LC accessory function is not constitutive but requires an activation step which can be provided by interferon-gamma during LC-T cell interaction.

Antigen-Presenting Cells↗
PubMed1993

Epidermal Langerhans cells and HIV-1 infection.

Originating from the bone marrow, Langerhans cells migrate into the peripheral epithelia (skin, mucous membranes) and play a key role in the immune surveillance system against foreign antigens. They act as antigen-presenting cells through a specific cooperation with CD4+ lymphocytes after migration to the proximal lymph nodes. As HIV-1-permissive cells, Langerhans cells in genital or rectal mucosa may be the first infected cell type and may be the vectors of infection for CD4-positive T cells. It has been clearly demonstrated that Langerhans cells may be infected in HIV-1 sero-positive patients. Recently in vitro experimental infection of Langerhans cells was achieved using a co-culture assay with HIV-1-infected cells. Investigation into the exact role of Langerhans cells in the course of HIV-1 infection will contribute greatly to our understanding of AIDS pathogenesis.

Acquired Immunodeficiency Syndrome↗
PubMed1993

S100 protein and neuron-specific enolase on monocytic leukemic CD1+ cells, probable precursors of Langerhans cells.

Langerhans cells are characterized by specific markers, such as Birbeck granules and CD1a antigen. S100 protein and neuron-specific enolase are less specific but are expressed only on Langerhans cells among the cells of the phagocytic mononuclear system. In this study, the expression of these two antigens on many monocytic leukemic cells is shown. These cells could be precursors of Langerhans cells which have been transformed into malignant cells.

Antigens, CD↗
PubMed1992

GM-CSF and TNF-alpha cooperate in the generation of dendritic Langerhans cells.

Dendritic cells comprise a system of highly efficient antigen-presenting cells which initiate immune responses such as the sensitization of T cells restricted by major histocompatibility complex molecules, the rejection of organ transplants and the formation of T-cell-dependent antibodies. Dendritic cells are found in many non-lymphoid tissues, such as skin (Langerhans cells) and mucosa, and they migrate after antigen capture through the afferent lymph or the bloodstream to lymphoid organs, where they efficiently present antigen to T cells. Dendritic cells are difficult to isolate and, although they originate from bone marrow their site of maturation and the conditions that direct their growth and differentiation are still poorly characterized. Granulocyte macrophage-colony stimulating factor (GM-CSF) favours the outgrowth of dendritic cells from mouse peripheral blood. Here we extend this finding to man and demonstrate that cooperation between GM-CSF and tumour necrosis factor-alpha (TNF-alpha) is crucial for the generation of human dendritic/Langerhans cells from CD34+ haematopoietic progenitors. The availability of large numbers of these cells should now facilitate the understanding of their role in immunological regulation and disorder.

Antigens, CD↗
PubMed1992

In vitro adhesion of human epidermal Langerhans cells to laminin and fibronectin occurs through beta 1 integrin receptors.

Human epidermal Langerhans cells are dendritic cells that can capture, process, and present antigens to T cells. It was previously shown that these Langerhans cells express the very late activation antigen (VLA) protein family of beta 1 integrins. beta 1 integrins mainly mediate the adhesion of cells to a number of extracellular components, such as laminin, fibronectin, and collagen, which are present in the skin. In this report, we demonstrate that a large percentage of the Langerhans cell population was able in vitro to attach to laminin and fibronectin but not to collagen. An ultrastructural study of adherent Langerhans cells showed that they were spread largely on laminin, with a loss of their round shape, and partially on fibronectin. Langerhans cell binding to laminin or fibronectin induced a decrease of the Birbeck granule number. Specific inhibitions of cell adhesion were performed, and it was demonstrated that VLA-6 was the major receptor involved in Langerhans cell adhesion to laminin. This adhesion was not RGD dependent and was slightly enhanced by Mn2+. VLA-3 and especially VLA-5 mediated Langerhans cell binding to fibronectin through the RGDS sequence of the protein. Mn2+ sharply increased the Langerhans cell adhesion to fibronectin. VLA-6 mediated in vitro Langerhans cell adhesion to laminin, which suggests that in vivo VLA-6 could permit Langerhans cells to attach and migrate through the basement membrane. Moreover, VLA-5 and VLA-3 take part in the in vitro Langerhans cell binding to fibronectin, suggesting that in vivo these fibronectin receptors could facilitate Langerhans cell passage throughout the fibronectin network of the dermis before migration to lymph nodes.

Amino Acid Sequence↗
PubMed1992

Human epidermal Langerhans cells express beta 1 integrins that mediate their adhesion to laminin and fibronectin.

Members of the beta 1 or very late antigen (VLA) integrin family represent the predominant class of integrin extracellular matrix receptors. Adhesion assays were developed for the identification of the beta 1 integrins involved in the adhesive interactions between Langerhans cells (which mainly express alpha 4 beta 1, alpha 5 beta 1, and alpha 6 beta 1) and extracellular matrix proteins. For this purpose, binding assays were performed on fibronectin-, laminin-, collagen type IV-, and collagen type I-coated plates. 59% +/- 21% of Langerhans cells (LC) specifically attached to fibronectin. Using as inhibitory probes monoclonal antibodies against the beta 1, alpha 5, and alpha 3 chains and the synthetic peptide GRGDSP resulted in a decrease of 43%, 41%, 15%, and 42% respectively of LC binding to fibronectin. 76% +/- 20% of LC specifically adhered to laminin. Anti-alpha 6 monoclonal antibody potently inhibited this adhesion, which dropped to 36%, whereas the synthetic peptide GRGDSP was ineffective. A low number of LC adhered to type I and type IV collagen (13-15%). These results indicate that alpha 5 beta 1 and alpha 6 beta 1 were the major beta 1 integrins involved in LC adhesion to fibronectin and laminin. Ultrastructural cell morphology of adherent cells was examined and showed that LC were largely spread on laminin and became tightly bound to the substrate on a large portion of membrane. On fibronectin surface, the contact between LC and substrate was smaller, thus cells could conserve their general round aspect. Moreover, LC binding to fibronectin and laminin induced a significative decrease of the Birbeck granule number. The finding that LC attach to LM and FN in vitro suggests they exist similarly in vivo. By mediating a passage through basement membrane and migration throughout the fibronectin network of the dermis, alpha 5 beta 1 and alpha 6 beta 1 could contribute to the ability of LC to migrate into and out of the epidermis.

Cell Adhesion↗
PubMed1992

In vitro HIV-1 entry and replication in Langerhans cells may clarify the HIV-1 genome detection by PCR in epidermis of seropositive patients.

Being dendritic antigen-presenting cells in skin and mucous membrane, Langerhans cells (LC) occur in areas at risk for inoculation by human immunodeficiency virus (HIV), and the question whether LC act as a target, reservoir, or vector for transmission of HIV has given rise to much controversy. To address this question, we first analyzed the epidermal compartment of skin from patients seropositive for HIV DNA. Second, we tested the susceptibility of each cell type normally found in this compartment to in vitro infection by HIV-1. A non-denatured DNA was obtained from epidermal sheets after a thermochemical treatment of biopsies (0.5 M ethylenediaminetetraacetic acid (EDTA), pH 7.5 at 60 degrees C for 90 seconds). Optimization of amplification of viral genome was performed with three primer pairs derived from gag, env, and pol sequences. Polymerase chain reaction (PCR) products were analyzed by Southern blot. Viral genome was found in five of 11 HIV-seropositive patients. To control the permissivity of epidermal cell population for HIV, cells isolated from the epidermal sheet of normal skin by trypsinization were co-cultured with HIV-1-carrying promonocytic cells (U937) and observed by electron microscopy. After 3-6 h of co-culture, numerous virions were either tightly bound or apparently engaged in the process of internalization through receptor-mediated endocytosis. At day 4 of co-culture, some infected LC appeared to release mature viral particles through bud formation. The in vitro HIV-1 entry and replication in LC may confirm the presence of the HIV-1 genome by PCR in epidermis of seropositive patients. The consequences of the permissivity of LC for HIV on the antigen-presenting function remain to be determined.

DNA, Viral↗
PubMed1992

CD1-reactive leukemic cells in bone marrow: presence of Langerhans cell marker on leukemic monocytic cells.

Langerhans cells originate in bone marrow and probably belong to the monocyte-macrophage lineage. CD1 is a specific marker of Langerhans cells. By immunofluorescence and immunoelectron microscopy, CD1a antigen and myeloid markers (CD11, CD13, CD14, CD15, CD33, HLA-DR) were studied in 53 cases of acute myeloid leukemias (AML) and 3 acute lymphoblastic leukemias (ALL). The 11 ANLL without monocytic component were CD1a negative. 2/5 of acute myelomonocytic leukemias (AML4) and 9/37 of acute monocytic leukemias (AML5) were positive. All 3 ALL were negative. No correlation was found between CD1a and myeloid markers. CD1a+ AML did not differ from CD1a- AML with regard to cytogenetics or response to therapy. The CD1a positive cells may originate from an abnormal proliferation of CD1a positive cells which are present in bone marrow and which may differentiate into Langerhans cell precursors.

Antigens, CD↗