Topic:Dendritic Cells
Dendritic cells are a type of immune cell present in horses that function as antigen-presenting cells, playing a significant role in initiating and regulating the adaptive immune response. These cells are capable of capturing, processing, and presenting antigens to T-cells, thus facilitating the activation of the immune system. In equine immunology, dendritic cells are studied for their involvement in immune surveillance and their potential impact on vaccination efficacy and disease resistance. This page compiles peer-reviewed research studies and scholarly articles that explore the biology, function, and potential clinical applications of dendritic cells in equine health.
Rational design of synthetic peptides to generate antibodies that recognize in situ CD11c(+) putative dendritic cells in horse lymph nodes. A three-dimensional model of the alphaX I-domain of the horse integrin CD11c from dendritic cells provided information for selecting two segments of the primary structure for peptide synthesis. Peptide 1 contains 20 amino acids and peptide 2 has 17 amino acid residues. The first spans from position Thr229 to Arg248 of an alpha-helix segment of the structure, whereas peptide 2 goes from Asp158 to Phe174 and corresponds to an exposed segment of the loop considered to be the metal ion-dependent adhesion site. Murine polyclonal antisera against both peptides were generated and assayed in periphera...
Ex vivo generation of mature equine monocyte-derived dendritic cells. Dendritic cells (DCs) are innate immune cells specialized in antigen detection and presentation. They perform an essential role in initiating and guiding the immune response, the direction of which largely depends upon the activation state of the DCs. The objective of this study was to generate mature equine monocyte-derived DCs and, in doing so, to develop a method for measuring the activation state of these cells. Equine DCs were stimulated with UV-inactivated Escherichia coli (E. coli), and the activation status was measured by analyzing cell surface marker expression, cytokine production, ...
Young foal and adult horse monocyte-derived dendritic cells differ by their degree of phenotypic maturity. Newborn foals are very susceptible to infections by opportunistic pathogens such as Rhodococcus equi. This susceptibility is thought to be due to the immaturity of their immune system, in particular their inability to produce interferon-gamma. This deficiency may result from an insufficiency in accessory signals. We therefore compared monocyte-derived dendritic cells (MoDC) from foals and from adult horses. CD172, MHC-I and MHC-II were generally expressed on more than 90% MoDC from foals and adults. CD1w2(+)CD86(+) cells tended to be less represented in 2-3-week-old foals than in adults. This ...
Foal monocyte-derived dendritic cells become activated upon Rhodococcus equi infection. Susceptibility of foals to Rhodococcus equi pneumonia is exclusive to the first few months of life. The objective of this study was to investigate the immediate immunologic response of foal and adult horse antigen-presenting cells (APCs) upon infection with R. equi. We measured the activation of the antigen-presenting major histocompatibility complex (MHC) class II molecule, costimulatory molecules CD40 and CD86, the cytokine interleukin-12 (IL-12), and the transcriptional factor interferon regulatory factor 1 (IRF-1) in monocyte-derived macrophages (mMOs) and dendritic cells (mDCs) of adult h...
Clinical application of dendritic cells and interleukin-2 and tools to study activated T cells in horses–first results and implications for quality control. Dendritic cells (DCs) are antigen-presenting cells, which are well known for their capacity to stimulate immunity. The ex vivo generation of myeloid DC from monocytes has facilitated the development of DC-vaccination protocols which have been extensively evaluated in tumour immunology and are regarded by some as a gold mine for clinical research. However, there is a considerable amount of work required to overcome the potential risks associated with such therapy. It is therefore mandatory to characterize the system to be applied and to study the reactions, particularly at the level of T cell r...
Activation of peripheral blood monocytes results in more robust production of IL-10 in neonatal foals compared to adult horses. Foals are particularly vulnerable to infection by Rhodococcus equi during the first 2 weeks of life whereas mature horses are not. While an innate immunodeficiency likely accounts for this clinically relevant vulnerability, the factors that contribute to infection by R. equi have not been fully elucidated. In this study, we demonstrate that cells of the monocyte lineage, including monocytes, macrophages, and dendritic cells, that have been activated with LPS and IFN-gamma, respond with a statistically significant, greater amount of cytokine mRNA production of IL-10, IL-12p35, and IL-12p40 than...
An improved method to generate equine dendritic cells from peripheral blood mononuclear cells: divergent maturation programs by IL-4 and LPS. Equine dendritic cells (eqDC) can be generated from peripheral blood monocytes by propagation in GM-CSF and IL-4. Despite similarities with the generation of human DC, we found significant improvements for eqDC generation and functional influences on eqDC maturation. The fractionation of peripheral blood mononuclear cells (PBMC) by two subsequent gradients at densities of 1.090 and 1.077 as well as an adherence step in AIM V((R)) medium on dishes coated with extracellular matrix components (Primaria) improved the purity and yield of DC. After 3 days, eqDC cultures with GM-CSF alone developed i...
Molecular cloning and characterization of the alphaX subunit from CD11c/CD18 horse integrin. This work reports the cloning and sequence determination of the horse alpha subunit of the integrin CD11c/CD18, a marker of dendritic cells. A cDNA clone of 4582 base pairs was obtained. It encodes a protein segment of 1086 amino acid residues of the extracellular domain with 10 potential sites of glycosylation, a transmembrane domain of 32 residues and a C-terminal cytoplasmic tail of 24 residues. A phylogenetic analysis of this integrin shows close similarity (83%) with that of Canis familiaris.
Restricted and selective tropism of a Venezuelan equine encephalitis virus-derived replicon vector for human dendritic cells. Dendritic cells (DCs) consist of heterogeneous phenotypic populations and have diverse immunostimulatory functions dependent on both lineage and functional phenotype, but as exceptionally potent antigen-presenting cells, they are targets for generating effective antigen-specific immune responses. A promising replicon particle vector derived from Venezuelan equine encephalitis virus (VEE) has been reported to transduce murine footpad DCs. However, the receptive DC subset, the degree of restriction for this tropism, and the extent of conservation between rodents and humans have not been well cha...
Monocyte-derived dendritic cells from horses differ from dendritic cells of humans and mice. Dendritic cells (DC) are the initiators of immune responses and are present in most tissues in vivo. To generate myeloid DC from monocytes (MoDC) in vitro the necessary cytokines are granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). Using degenerated primers delineated from other species and rapid amplification of cDNA ends reverse transcription-polymerase chain reaction (RACE RT-PCR), the cDNA of equine (eq.) GM-CSF was cloned and found to have a point deletion at the 3'-end of eq.GM-CSF, resulting in a 24-nucleotide extended open reading frame not described ...
Alterations of epidermal proliferation and cytokeratin expression in skin biopsies from heavy draught horses with chronic pastern dermatitis. We report the historical, clinical and histopathological characteristics of skin lesions in biopsies from 37 heavy draught horses with chronic pastern dermatitis. The skin lesions were divided into four macroscopic groups: scaling (group I, n=5), hyperkeratotic and hyperplastic plaque-like lesions (group II, n=14), nodular skin masses (group III, n=16) and verrucous skin lesions (group IV, n=2). The principal histological findings were hyperkeratosis and epidermal hyperplasia. There was a gradual increase in epidermal hyperplasia from groups I to IV, suggesting that the lesions represent diffe...
Molecular cloning and characterization of markers and cytokines for equid myeloid cells. The myeloid cell system comprises of monocytes, macrophages (MPhi), dendritic cells (DC), Kupffer cells, osteoclasts or microglia and is also known as the mononuclear phagocytic system (MPS). Essential cytokines to differentiate or activate these cells include GM-CSF or IL-4. Important markers for characterization include CD1, CD14, CD68, CD163 and CD206. All these markers, however, were not cloned or further characterized in equids by use of monoclonal antibodies earlier. To overcome this problem with the present study, two approaches were used. First, we cloned equine cytokines and markers, ...
Equine infectious anemia virus-infected dendritic cells retain antigen presentation capability. To determine if equine monocyte-derived dendritic cells (DC) were susceptible to equine infectious anemia virus (EIAV) infection, ex vivo-generated DC were infected with virus in vitro. EIAV antigen was detected by immunofluorescence 3 days post-infection with maximum antigen being detected on day 4, whereas there was no antigen detected in DC incubated with the same amount of heat-inactivated EIAV. No cytolytic activity was observed after EIAV(WSU5) infection of DC. These monocyte-derived DC were more effective than macrophages and B cells in stimulating allogenic T lymphocytes. Both infected...
Histology and ultrastructure of the equine lingual tonsil. II. Lymphoid tissue and associated high endothelial venules. The stratified squamous epithelium of the lingual tonsil of five young horses was infiltrated with CD4 and CD8 positive cells, which were very numerous in the crypt reticular epithelium along with macrophages and IgGb and IgA positive cells. Lymphoid follicles of the lamina propria mucosae consisted of a parafollicular area, corona and germinal centre. The parafollicular area was populated by large numbers of CD4 and CD8 positive lymphocytes as well as macrophages, inter-digitating cells, and a few B-lymphocytes. The germinal centre contained mainly IgGb and IgG(T) positive cells, plasma cells...
Identification of equine herpesvirus-1 antigens recognized by cytotoxic T lymphocytes. Equine herpesvirus-1 (EHV-1) causes serious disease in horses throughout the world, despite the frequent use of vaccines. CTLs are thought to be critical for protection from primary and reactivating latent EHV-1 infections. However, the antigen-specificity of EHV-1-specific CTLs is unknown. The aim of this study was to identify EHV-1 genes that encode proteins containing CTL epitopes and to determine their MHC I (or ELA-A in the horse) restriction. Equine dendritic cells, transfected with a series of EHV-1 genes, were used to stimulate autologous CTL precursor populations derived from previous...
Cellular architecture of the synovium in the tendon sheath of horses: an immunohistochemical and scanning electron microscopic study. The intimal lining cells of the synovium in joints have been studied morphologically and histochemically and shown to consist of macrophagic cells (type A) and fibroblast-like cells (type B). It is believed that the structure of the synovium in the tendon sheath is similar to that in the joint, but there have been only a few morphological studies of the tendon sheath. The present study revealed the cellular architecture of synovium in the tendon sheath of horses by histochemistry and scanning electron microscopy (SEM). Like the joint, the inner surface of the tendon sheath was covered with a c...
Langerhans cells within the follicular epithelium and the intradermal sweat duct in equine insect hypersensitivity “Kasen”. Histopathologic and electron microscopic observations were given on Langerhans cells (LCs) within the follicular epithelium (FE) and intradermal sweat duct (ISD) of equine "Kasen". By light microscopy, LCs were present in the greatest numbers within the FE and ISD than within the epidermal layer and the normal skin, with an occasional formation of several aggregated foci. By electron microscopy, LCs within the FE and ISD widely extended their dendritic processes between the keratinocytes and contained Birbeck granules (Bgs), mitochondria, rough endoplasmic reticula and ribosomes in the cytopla...
Modulating immune responses with dendritic cells: an attainable goal in veterinary medicine? Dendritic cells (DCs) are antigen presenting cells that potently modulate immune responses with varying outcomes depending on the DC sub-population involved. To understand how DC sub-types arise, it is necessary to determine which factors influence their differentiation. At least three major sub-populations of DCs have been described in mice: CD4+/CD8- "myeloid" DCs, CD4-/CD8+ "lymphoid" DCs and Langerhans cell-derived DCs. Whilst somewhat comparable populations have been described in man, in most other species very little is known. The identification of cytokines which stimulate proliferation...
Clinical, pathologic, immunohistochemical, and virologic findings of eastern equine encephalomyelitis in two horses. Natural eastern equine encephalitis alphavirus (EEEV) infection was diagnosed in two adult horses with anorexia and colic, changes in sensorium, hyperexcitability, and terminal severe depression. Myocardium, tunica muscularis of stomach, intestine, urinary bladder, and spleen capsule had coagulative necrosis and perivascular lymphocytic infiltrate. Central nervous system (CNS) lesions were diffuse polioencephalomyelitis with leptomeningitis characterized by perivascular T lymphocyte cuffing, marked gliosis, neuronophagia, and multifocal microabscesses. Lesions were more prominent within cerebr...
Role of dendritic cell targeting in Venezuelan equine encephalitis virus pathogenesis. The initial steps of Venezuelan equine encephalitis virus (VEE) spread from inoculation in the skin to the draining lymph node have been characterized. By using green fluorescent protein and immunocytochemistry, dendritic cells in the draining lymph node were determined to be the primary target of VEE infection in the first 48 h following inoculation. VEE viral replicon particles, which can undergo only one round of infection, identified Langerhans cells to be the initial set of cells infected by VEE directly following inoculation. These cells are resident dendritic cells in the skin, which mi...
Functional characterization of equine dendritic cells propagated ex vivo using recombinant human GM-CSF and recombinant equine IL-4. Naive T cells can be activated both in vivo and in vitro by specialized antigen presenting cells, dendritic cells (DC), with potent antigen-specific, immunostimulatory activity. Indeed, DC can provide an extremely powerful and important immunological tool by which to potentiate the immune response for specific recognition of foreign antigens. Until recently, the direct isolation of DC from PBMC required laborious procedures with extremely poor yields (<0.1%). Methods have been developed for the human, lower primate, and murine model systems to propagate large numbers of DC from PBMC or bone...
Equine herpesvirus type 1 infects dendritic cells in vitro: stimulation of T lymphocyte proliferation and cytotoxicity by infected dendritic cells. Equine herpesvirus type 1 (EHV-1) causes respiratory disease, abortion and myeloencephalopathy in horses. As with other herpesviruses, cell-mediated immunity is considered important for both recovery and protection. Although virus-specific T-cell proliferation and cytotoxicity can be detected following in vivo infection, little is known about the role of antigen presenting cells such as dendritic cells (DCs) in these processes. Peripheral blood DCs were shown to express the viral glycoprotein gB perinuclearly following exposure to EHV-1 in vitro, demonstrating EHV-1 replication within them. Co...
Isolation and characterisation of equine dendritic cells. Despite their important role in initiating T-cell responses in other species, dendritic cells have not been studied in the horse. A method for isolating blood dendritic cells by adherence and metrizamide gradients was adapted to equine cells. A number of monoclonal antibodies (mAbs), including some which label dendritic cells in other species, were tested for immunochemical reactivity with the isolated blood dendritic cells, and sections of lymph node and spleen. 62 +/- 6% of the isolated blood cells were MHC Class II positive and had typical dendritic cell morphology and only 4 +/- 2% contain...
Neurotrophin receptor-like proteins in Peyer’s patches. The neurotrophins are a family of growth factors that act on responsive cells through specific high-affinity signal-transducing receptors called Trk (A, B, and C) proteins. The neurotrophin receptor proteins are widely distributed in both nervous and nonnervous tissues, including the lymphoid organs. The expression of these receptor proteins by a cell population is an indication of responsiveness to the respective binding neurotrophin. The present study investigated the presence and cellular localization of high-affinity neurotrophin receptor proteins in equine and bovine Peyer's patches. Peye...
Immunohistochemical demonstration of African horse sickness viral antigen in formalin-fixed equine tissues. The distribution of viral antigen was studied in various tissues of three ponies, aged 3-4 years, infected experimentally with a virulent strain of African horse sickness virus (AHSV) serotype 4. Tissues were collected from the animals in the terminal stage of the peracute form of the disease and from one noninfected horse, included as a control. A polyclonal antibody with specificity for AHSV, plus the nonstructural protein NS2, was used in a sensitive avidin-biotin-peroxidase-complex (ABC) method performed on formalin-fixed, paraffin-embedded tissue sections. AHSV antigen was located primari...
Blue-cone horizontal cells in the retinae of horses and other equidae. The morphology of horizontal cells chiefly of the horse, but also of asses, mules, and a zebra, has been examined by Lucifer yellow injections into lightly fixed retinae and by immunocytochemistry. In common with other mammals, equids have a B-type horizontal cell, i.e., a cell with dendrites synapsing with cones and possessing a single axon synapsing with rods. Most mammalian retinae have a further type of horizontal cell, the A-type, also synapsing with cones but without an axon. The second type of horizontal cell in equids also has no axon; otherwise, it is most unusual. Compared with other...
An immunohistological study of MHC class II expression and T lymphocytes in the endometrium of the mare. The distribution of T lymphocytes and of cells bearing MHC Class II antigens in the endometrium of the mare was studied using an avidin-biotin-peroxidase staining method. The cells within the endometrium which expressed MHC Class II were macrophages, lymphocytes, monocytes, dendritic cells, epithelial cells and endothelial cells. MHC Class II expression increased significantly (P < 0.05) in the luminal epithelium and tended (P = 0.0573) to increase in the subepithelial layers during oestrus. Numbers of T lymphocytes did not differ between oestrus and dioestrus. MHC Class II expression and T...
Langerhans’ cells in equine cutaneous papillomas and normal skin. Langerhans' cells (LC) were investigated immunohistochemically and electron microscopically in normal equine epidermis and 133 equine cutaneous papillomas experimentally induced in five 2-year-old Thoroughbred horses. Class II major histocompatibility complex antigen-positive dendritic LC were found in the normal epidermis and ultrastructurally had the characteristic Birbeck's granules. In the developing phase of the papillomas, LC were significantly decreased in number and size, indicative of a hypofunctional state. In the regressing phase of the papillomas, LC were markedly increased in numb...
The effects of thermal stimulation on the ultrastructure of the fundus and duct of the equine sweat gland. Sweating in the horse had little effect on the ultrastructure of the glandular duct, other than on the lumen which enlarged. The fundus secretory cells, which in the resting gland were packed with vesicles, gradually lost them as sweating progressed until, after 4 hours of activity, few remained. Sweat appeared to be largely the product of secretion (a) by fluid transport, probably involving a region of complex cellular interdigitations adjacent to the basement membrane and (b) by exocytosis of vesicles, although a secondary mechanism of vesicle loss by micro-apocrine secretion may occur. Howe...