Langerhans cells (LCs) and dendritic epidermal T cells (DETCs) constitute the skin immune system. To demonstrate the kinetics of in vivo activation of murine LCs and DETCs in the elicitation phase of contact hypersensitivity, we measured the cell area positively stained for I-A and gammadeltaT-cell receptor (or Thy-1.2), respectively, under ...

Prion diseases are closely linked to the conversion of host-encoded cellular prion protein (PrPC) into its pathological isoform (PrPSc). PrP conversion experiments in scrapie infected tissue culture cells, transgenic mice, and cell-free systems usually require unique epitopes and corresponding monoclonal antibodies (MAbs) for the immunological discrimination of exogenously introduced and ...

Imiquimod (S-26308, R-837) (1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4 amine), an immune response modifier, demonstrates potent antiviral and antitumor activity in animal models (see structure in Fig. 1). The drug exhibits no direct antiviral or antiproliferative activity when tested in a number of cell culture systems. Imiquimod's activity was discovered while screening for anti-herpes virus ...

Epidermal Langerhans cells (LCs) play a pivotal role in the induction of cutaneous immune responses, including those provoked by chemical allergens. The delivery by LCs of allergen to draining lymph nodes requires cell migration from the skin, a process that is dependent upon the availability of epidermal cytokines -particularly TNF-alpha ...

Imiquimod is 1-(2-methylpropyl)-1H-imidazo[4,5-c]quinolin-4-amine and has a molecular formula of C14H16N4. It was discovered by researchers at 3M Pharmaceuticals (St Paul, MN, USA) and is the newest in a class of drugs known as immune response modifiers. Imiquimod 5% cream has been formulated for the treatment of external genital and perianal ...

Imiquimod is the newest in a class of drugs known as immune response modifiers. In preclinical studies, imiquimod induced the production of cytokines - the principal cytokine for antiviral activity being interferon alpha. Imiquimod does not inhibit viruses directly, nor does it cause direct, non-specific cytolytic destruction [1]. Preclinical studies ...

Drawing the meeting to a close, co-chairman Dr. Selim Aractingi said that it is now clear that local immune factors are important in determining the regression of warts, and that imiquimod appears to mimic the mechanism of immunity occuring in people in whom warts regress without treatment. He summarised the ...

Although both CD80 (B7-1) and CD86 (B7-2/B70) have been recently identified in cultured human Langerhans cells (LC), little is known of the role and regulatory properties of CD80 and CD86 on human LC. We present here the results of a study comparing the expression and function of CD80 and CD86 ...

After UV exposure of skin, epidermal Langerhans cells (LC) are depleted, whereas CD11b+CD36 CD1a- monocytes/macrophages (UV-Mphi) infiltrate. Different immunological outcomes in vivo are mediated by LC (sensitization) and UV-Mphi (tolerance) which may be related to the distinct T cell activation states that these antigen-presenting cells (APC) induce. We previously demonstrated ...

Apoptosis plays an important role in development, homeostasis, and disease. Current work has suggested that apoptosis can be evoked by multiple stimuli that, in turn, initiate distinct death pathways. Recently, exciting advances have been made in the understanding of biochemical pathways that regulate apoptotic processes. These pathways contain both evolutionarily ...

Morphologic studies have indicated that Langerhans cells (LC) are frequently in anatomic apposition with epidermal nerves containing the neuropeptide calcitonin gene-related peptide (CGRP). Experiments were undertaken to examine whether CGRP modulates LC function. The effect of pre-exposure of LC to CGRP in vitro on alloantigen presentation and specific protein presentation ...

Prion diseases are neurodegenerative disorders, affecting humans and animals. The human diseases include kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS), and fatal familial insomnia (FFI). To generate monospecific antisera against human prion proteins we have immunized mice with DNA coding for different human prion proteins. We constructed immunization vectors expressing ...

During the induction phase of contact sensitization and other cutaneous immune responses a proportion of epidermal Langerhans cells (LC) is induced to leave the skin and migrate via afferent lymphatics to lymph nodes draining the site of exposure. The cells that accumulate in draining nodes have acquired the characteristics of ...

In Leishmania-infected macrophages (M phi), the formation of reactive nitrogen intermediates by the inducible isoform of nitric oxide synthase (iNOS) is critical for the killing of the intracellular parasites. We have recently shown that, in addition to M phi, epidermal Langerhans cells (LC) can phagocytose Leishmania major, but they do ...

This article reviews the role of dendritic cells in cutaneous immunity. Langerhans cells (LC) found in the epidermis are the best-characterized dendritic cell population. They have the ability to process antigen in the periphery, transport it to the draining lymph nodes (DLN) where they are able to cluster with, and ...

IL-12 is a 70-kDa heterodimeric cytokine composed of a p35 chain and p40 chain. This cytokine exerts a powerful positive regulatory influence on the development of Th1 helper T-cell immune responses and is a potent inducer of IFN-gamma production and cytotoxic T cell differentiation and function. Because epidermal Langerhans cells ...

Cotinine levels in blood and cervical fluid of smokers and non-smokers were analysed using capillary-column gas chromatography. These levels were not related to numerical cell densities of intraepithelial S100-protein- and LN2-positive Langerhans cells or to MAC-387-positive macrophages in the stroma of the transformation zone of normal uterine cervices. A decrease ...

The CD36 molecule has been shown to be associated with subsets of peripheral blood monocyte/macrophages and, in cells isolated from either ultraviolet (UV)-irradiated or diseased skin, to induce downregulatory immune responses. Although macrophages are certainly present within normal human dermis, whether they normally express CD36 is still a matter of ...

The skin is an immunologically active tissue. Epidermal cells, both keratinocytes and Langerhans cells (LC), produce constitutively or can be stimulated to produce a variety of cytokines, many of which play important roles in the induction and regulation of allergic responses to sensitizing chemicals. Tumor necrosis factor alpha (TNF-alpha) provides ...

The epidermis of mice consists of three cellular components, i.e., keratinocytes, Langerhans cells (LC), and dendritic epidermal T cells (DETC). Each epidermal subpopulation produces a different set of cytokines, thereby forming a unique cytokine milieu. These cytokines, in turn, support the survival and growth of LC and DETC and regulate ...

Sunburned skin is characterized by expanded numbers of macrophages (ultraviolet [UV]-MPH), and these UV-MPH differ from Langerhans cells (LC) in their abilities to initiate T-cell-mediated immune reactions. UV-MPH and LC may themselves be differentially responsive to the surrounding milieu, which may in turn modulate their immunoregulatory activity. We asked whether ...

Cell lineage analysis has revealed that the amniote organizer, Hensen's node, is subdivided into distinct regions, each containing a characteristic subpopulation of cells with defined fates. Here, we address the question of whether the inducing and regionalising ability of Hensen's node is associated with a specific subpopulation. Quail explants from ...

It has long been assumed that papilloma regression is mediated by immunological mechanisms which are probably cellular in nature. The potentiation of these responses may alter the course of papilloma progression. Certain strains of the bacterium Corynebacterium parvum (Propionibacterium acnes) have been shown to augment cellular immune mechanisms by increasing ...

Little is known of the in vivo role of the immune system in controlling human papillomavirus infection in the genital tract. The authors have studied 125 closely monitored patients with genital warts. Of these 125 patients, wart regression was seen in 28 patients. This study provides evidence that clearance of ...

The induction phase of skin sensitization is associated with the passage of antigen-bearing Langerhans cells (LC) from the epidermis to the draining lymph nodes. Recent investigations have revealed that the induction of LC migration following topical sensitization is dependent on tumour necrosis factor alpha (TNF-alpha), an epidermal cytokine. While in ...

Cottontail rabbit papillomavirus (CRPV)-induced papillomas progress at a high frequency to carcinomas and thus can serve as a model for high-cancer-risk human papillomavirus infection. Previously, we have shown that antibodies to nonstructural and structural proteins are detected in only a fraction of papilloma-bearing animals. However, the antibody response to structural ...

Local trauma and topical exposure to sensitizing chemicals induces the production by epidermal cells of a variety of cytokines including interleukins 1 (alpha and beta), 6, 8 and 10 (IL-1alpha, IL-1beta, IL-6, IL-8 and IL-10), granulocyte/macrophage colony-stimulating factor and tumour necrosis factor alpha. There is mounting evidence that keratinocyte-derived cytokines ...

Persistence of chronic tinea pedis (CTP) and pityriasis (tinea) versicolor (PIVE) has been tentatively attributed to an impaired cellular immune response. Therefore immunophenotyping of the inflammatory infiltrates in both disorders was performed in order to detect possible defects in cellular defence. The results of the present study show a dominance ...

Phosphatidylserine (PS) modulates several immune functions in vitro, including T cell activation, antibody and cytokine production, and macrophage growth. In the present work we studied the effects of PS on the induction of contact hypersensitivity (CH) in mice. BALB/c mice painted with PS (9.4-75 mg/kg) and with a sensitizing dose ...

Several observations suggest interactions between the immune and nervous systems. Psoriasis and atopic dermatitis may worsen with anxiety and have been associated with anomalous neuropeptide regulation. Neurotransmitters affect lymphocyte function and lymphoid organs are innervated. Calcitonin gene-related peptide (CGRP) is a neuropeptide and vasodilator that modulates some macrophage functions, including ...

Analysis of the early stages of experimental skin cancer in mice has demonstrated that complete chemical carcinogens (e.g. DMBA or benzo(a)pyrene) and tumour promoters (e.g. TPA) but not tumour initiators (e.g. urethane) deplete or functionally alter epidermal Langerhans cells (LC). These changes result in altered local immunity as antigen presentation ...

The roles of dendritic or Langerhans cells in human neoplasia have been studied in animal models and human subjects for some years. Much has already been learned concerning the operative immunological processes, relationships with other components of the reticuloendothelial system, and correlations with genetics and the aging process. Unfortunately, the ...

This article reviews the role of epidermal Langerhans cells (LC) in the development of cutaneous immune responses to chemical allergens. Following topical exposure to sensitizing chemicals, LC, many of which bear allergen, are induced to migrate from the skin, via the afferent lymphatics, to the draining lymph nodes. The phenotypic ...

In American cutaneous leishmaniasis (ACL), Leishmania parasites enter the epidermis of the host via the bite of infected sandflies. Immune responses against the parasite vary from "effective" in localized (LCL) to a state of "selective anergy" in diffuse (DCL) cutaneous leishmaniasis, whereas the intermediate muco-cutaneous form (MCL) is characterized by ...

Unlike other cutaneous surfaces, the central portion of the corneal epithelium is typically devoid of Langerhans cells. The absence of Ia+ Langerhans cells in the central cornea is of more than casual interest and may explain the immunologic privilege that is characteristic of corneal allografts. The present communication summarizes previous ...

Epidermal Langerhans cells (LC) are considered direct yet immature precursors of dendritic cells (DC) in the draining lymph nodes. Although the development of LC into potent immunostimulatory DC occurs in vitro and has been studied in detail, little is known about their profile of cytokine gene expression. By using reverse ...

Langerhans' cells (LC) are bone marrow-derived dendritic antigen-presenting cells (APC) found in the epidermis of mammals. It is not known why they accumulate in the epidermis. Human and murine skin tumours are infiltrated with large numbers of LC, however previous experiments have shown that this does not seem to be ...

Intravenous infusion of hapten-derivatized epidermal cells (EC) in syngeneic mice leads to two competing signals for contact hypersensitivity (CH), a dominant effector signal attributable to Langerhans cells (LC) and a suppressor signal from Thy-1+ EC. In vitro exposure of LC to low dose ultraviolet B (UVB) radiation before hapten-derivatization and ...

Previous work in our department demonstrated a reduction in the numbers of Langerhans' cells in cervical epithelium showing histologic changes of human papillomavirus (HPV) infection and cervical intraepithelial neoplasia (CIN). In conjunction with a localized reversal of the T4:T8 ratio of T-lymphocytes, that finding provides evidence of the association of ...

Langerhans cells are dendritic non epithelial cells found in the gingiva. The latest research in immunohistochemistry suggests that they may play an important role in the cellular immune response. The purpose of this quantitative study was to evaluate the number of Langerhans cells in association with gingival inflammation and the ...

T-lymphocyte transformation ability decreased and the function of the B-lymphocyte and mononuclear leucocyte/macrophage system increased when the activity of central serotonergic neurons was enhanced by the stimulation of nucleus dorsal raphe (NDR). These changes induced by NDR stimulation were not effected by electroacupuncture (EA) when EA was performed on the ...

Wide-ranging differences were observed between the antitumor activities of 23 lactobacilli (13 species; 23 strains) and their capacities to elevate the level of serum colony-stimulating activity (CSA) by intraperitoneal administration in mice, and a good correlation existed between the two activities. The mechanism of enhanced production of CSA by administration ...

The epidermis on the backs or ears of DBA/2 mice treated for 7 days with a 20% concentration of monobenzyl ether of hydroquinone (MBEH) had a significantly greater population density of ATPase- and Ia-positive cells compared with control mice treated with diluent. There was no decrease or increase in ATPase- ...

The macrophage system in man plays a significant role in the detection of foreign cells. The mechanisms by which macrophages recognize malignant cells, however, are not well understood. We used human monocytes and four lymphoblastoid cell (LC) lines derived from human acute lymphocytic leukemia to investigate the initial recognition of ...

Langerhans cells (LCs) are dendritic epidermal cells whose ability to function as accessory/stimulatory cells in initiating the immune response is, like that of macrophages, dependent on the expression of class II major histocompatibility antigens. In normal human skin approximately 50% of LCs identified by cell surface T6 antigenicity also express ...

A major question challenging immunobiologists relates to those mechanisms that control the selective movement of cells involved in immune and inflammatory processes at various tissue sites such as the skin. Little is known about those influences that control the selective migration of macrophage-like Langerhans cells (LC) to normal epidermis, where ...

Dinitrophenylated macrophages are efficient inducers of contact sensitivity and of tolerance to dinitrochlorobenzene, depending on the mode of application. Contact sensitivity induced by an intradermal injection of DNP-M phi is genetically restricted, whereas tolerance induced by an intravenous injection is, in guinea pigs, not under control. This tolerance is complete ...

Dendritic cells (DCs) form a network comprising different populations that initiate and differentially regulate immune responses. Langerhans cells (LCs) represent a unique population of DCs colonizing epithelium, and we present here observations suggesting that macrophage inflammatory protein (MIP)-3α plays a central role in LC precursor recruitment into the epithelium during ...

Certain types of dendritic cells (DCs) appear in inflammatory lesions of various etiologies, whereas other DCs, e.g., Langerhans cells (LCs), populate peripheral organs constitutively. Until now, the molecular mechanism behind such differential behavior has not been elucidated. Here, we show that CD1a+ LC precursors respond selectively and specifically to the ...

Dendritic cells (DCs) have been proposed to play a pivotal role in the initiation and perpetuation of rheumatoid arthritis (RA) by presentation of arthritogenic antigens to T cells. We investigated the in vivo characteristics of two major DC subsets, myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), in RA synovial tissue ...