Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).
Non-hematopoietic cells, with extensive dendritic processes, found in the primary and secondary follicles of lymphoid tissue (the B cell zones). They are different from conventional DENDRITIC CELLS associated with T-CELLS. They are derived from MESENCHYMAL STEM CELLS and are negative for class II MHC antigen and do not process or present antigen like the conventional dendritic cells do. Instead, follicular dendritic cells have FC RECEPTORS and C3B RECEPTORS that hold antigen in the form of ANTIGEN-ANTIBODY COMPLEXES on their surfaces for long periods for recognition by B-CELLS.
The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)
An integrin alpha subunit of approximately 150-kDa molecular weight. It is expressed at high levels on monocytes and combines with CD18 ANTIGEN to form the cell surface receptor INTEGRIN ALPHAXBETA2. The subunit contains a conserved I-domain which is characteristic of several of alpha integrins.
Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-12 is a 70 kDa protein that is composed of covalently linked 40 kDa and 35 kDa subunits. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells and plays a role in the stimulation of INTERFERON-GAMMA production by T-LYMPHOCYTES and NATURAL KILLER CELLS.
Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake.
Recirculating, dendritic, antigen-presenting cells containing characteristic racket-shaped granules (Birbeck granules). They are found principally in the stratum spinosum of the EPIDERMIS and are rich in Class II MAJOR HISTOCOMPATIBILITY COMPLEX molecules. Langerhans cells were the first dendritic cell to be described and have been a model of study for other dendritic cells (DCs), especially other migrating DCs such as dermal DCs and INTERSTITIAL DENDRITIC CELLS.
Process of classifying cells of the immune system based on structural and functional differences. The process is commonly used to analyze and sort T-lymphocytes into subsets based on CD antigens by the technique of flow cytometry.
A critical subpopulation of T-lymphocytes involved in the induction of most immunological functions. The HIV virus has selective tropism for the T4 cell which expresses the CD4 phenotypic marker, a receptor for HIV. In fact, the key element in the profound immunosuppression seen in HIV infection is the depletion of this subset of T-lymphocytes.
A class of animal lectins that bind to carbohydrate in a calcium-dependent manner. They share a common carbohydrate-binding domain that is structurally distinct from other classes of lectins.
A technique of culturing mixed cell types in vitro to allow their synergistic or antagonistic interactions, such as on CELL DIFFERENTIATION or APOPTOSIS. Coculture can be of different types of cells, tissues, or organs from normal or disease states.
Measure of histocompatibility at the HL-A locus. Peripheral blood lymphocytes from two individuals are mixed together in tissue culture for several days. Lymphocytes from incompatible individuals will stimulate each other to proliferate significantly (measured by tritiated thymidine uptake) whereas those from compatible individuals will not. In the one-way MLC test, the lymphocytes from one of the individuals are inactivated (usually by treatment with MITOMYCIN or radiation) thereby allowing only the untreated remaining population of cells to proliferate in response to foreign histocompatibility antigens.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CD28 ANTIGEN with high specificity and to CTLA-4 ANTIGEN with low specificity. The interaction of CD86 with CD28 ANTIGEN provides a stimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
Class I-restricted activation of CD8-POSITIVE LYMPHOCYTES resulting from ANTIGEN PRESENTATION of exogenous ANTIGENS (cross-presentation). This is in contrast to normal activation of these lymphocytes (direct-priming) which results from presentation of endogenous antigens.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
A heterogeneous group of immunocompetent cells that mediate the cellular immune response by processing and presenting antigens to the T-cells. Traditional antigen-presenting cells include MACROPHAGES; DENDRITIC CELLS; LANGERHANS CELLS; and B-LYMPHOCYTES. FOLLICULAR DENDRITIC CELLS are not traditional antigen-presenting cells, but because they hold antigen on their cell surface in the form of IMMUNE COMPLEXES for B-cell recognition they are considered so by some authors.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
Glycoproteins found on the membrane or surface of cells.
A member of the tumor necrosis factor receptor superfamily with specificity for CD40 LIGAND. It is found on mature B-LYMPHOCYTES and some EPITHELIAL CELLS, lymphoid DENDRITIC CELLS. Evidence suggests that CD40-dependent activation of B-cells is important for generation of memory B-cells within the germinal centers. Mutations of the gene for CD40 antigen result in HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 3. Signaling of the receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
An encapsulated lymphatic organ through which venous blood filters.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
Glycoproteins expressed on cortical thymocytes and on some dendritic cells and B-cells. Their structure is similar to that of MHC Class I and their function has been postulated as similar also. CD1 antigens are highly specific markers for human LANGERHANS CELLS.
Vaccines or candidate vaccines designed to prevent or treat cancer. Vaccines are produced using the patient's own whole tumor cells as the source of antigens, or using tumor-specific antigens, often recombinantly produced.
The classes of BONE MARROW-derived blood cells in the monocytic series (MONOCYTES and their precursors) and granulocytic series (GRANULOCYTES and their precursors).
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
A cytokine produced by a variety of cell types, including T-LYMPHOCYTES; MONOCYTES; DENDRITIC CELLS; and EPITHELIAL CELLS that exerts a variety of effects on immunoregulation and INFLAMMATION. Interleukin-10 combines with itself to form a homodimeric molecule that is the biologically active form of the protein.
Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.
A costimulatory ligand expressed by ANTIGEN-PRESENTING CELLS that binds to CTLA-4 ANTIGEN with high specificity and to CD28 ANTIGEN with low specificity. The interaction of CD80 with CD28 ANTIGEN provides a costimulatory signal to T-LYMPHOCYTES, while its interaction with CTLA-4 ANTIGEN may play a role in inducing PERIPHERAL TOLERANCE.
CCR receptors with specificity for CHEMOKINE CCL19 and CHEMOKINE CCL21. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS.
An acidic glycoprotein of MW 23 kDa with internal disulfide bonds. The protein is produced in response to a number of inflammatory mediators by mesenchymal cells present in the hemopoietic environment and at peripheral sites of inflammation. GM-CSF is able to stimulate the production of neutrophilic granulocytes, macrophages, and mixed granulocyte-macrophage colonies from bone marrow cells and can stimulate the formation of eosinophil colonies from fetal liver progenitor cells. GM-CSF can also stimulate some functional activities in mature granulocytes and macrophages.
The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)
Substances that augment, stimulate, activate, potentiate, or modulate the immune response at either the cellular or humoral level. The classical agents (Freund's adjuvant, BCG, Corynebacterium parvum, et al.) contain bacterial antigens. Some are endogenous (e.g., histamine, interferon, transfer factor, tuftsin, interleukin-1). Their mode of action is either non-specific, resulting in increased immune responsiveness to a wide variety of antigens, or antigen-specific, i.e., affecting a restricted type of immune response to a narrow group of antigens. The therapeutic efficacy of many biological response modifiers is related to their antigen-specific immunoadjuvanticity.
A pattern recognition receptor that binds unmethylated CPG CLUSTERS. It mediates cellular responses to bacterial pathogens by distinguishing between self and bacterial DNA.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed)
A CC-type chemokine with specificity for CCR7 RECEPTORS. It has activity towards T LYMPHOCYTES and B LYMPHOCYTES.
A low affinity interleukin-3 receptor subunit that combines with the CYTOKINE RECEPTOR COMMON BETA SUBUNIT to form a high affinity receptor for INTERLEUKIN-3.
Any of several ways in which living cells of an organism communicate with one another, whether by direct contact between cells or by means of chemical signals carried by neurotransmitter substances, hormones, and cyclic AMP.
A pattern recognition receptor that binds several forms of imidazo-quinoline including the antiviral compound Imiquimod.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.
A subclass of lectins that are specific for CARBOHYDRATES that contain MANNOSE.
A CC-type chemokine with specificity for CCR7 RECEPTORS. It has activity towards DENDRITIC CELLS and T-LYMPHOCYTES.
Differentiation antigens found on thymocytes and on cytotoxic and suppressor T-lymphocytes. CD8 antigens are members of the immunoglobulin supergene family and are associative recognition elements in MHC (Major Histocompatibility Complex) Class I-restricted interactions.
Form of passive immunization where previously sensitized immunologic agents (cells or serum) are transferred to non-immune recipients. When transfer of cells is used as a therapy for the treatment of neoplasms, it is called adoptive immunotherapy (IMMUNOTHERAPY, ADOPTIVE).
The capacity of a normal organism to remain unaffected by microorganisms and their toxins. It results from the presence of naturally occurring ANTI-INFECTIVE AGENTS, constitutional factors such as BODY TEMPERATURE and immediate acting immune cells such as NATURAL KILLER CELLS.
The alpha subunits of integrin heterodimers (INTEGRINS), which mediate ligand specificity. There are approximately 18 different alpha chains, exhibiting great sequence diversity; several chains are also spliced into alternative isoforms. They possess a long extracellular portion (1200 amino acids) containing a MIDAS (metal ion-dependent adhesion site) motif, and seven 60-amino acid tandem repeats, the last 4 of which form EF HAND MOTIFS. The intracellular portion is short with the exception of INTEGRIN ALPHA4.
Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection.
Specialized tissues that are components of the lymphatic system. They provide fixed locations within the body where a variety of LYMPHOCYTES can form, mature and multiply. The lymphoid tissues are connected by a network of LYMPHATIC VESSELS.
Form of adoptive transfer where cells with antitumor activity are transferred to the tumor-bearing host in order to mediate tumor regression. The lymphoid cells commonly used are lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL). This is usually considered a form of passive immunotherapy. (From DeVita, et al., Cancer, 1993, pp.305-7, 314)
One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells. In addition to antiviral activity, it activates NATURAL KILLER CELLS and B-LYMPHOCYTES, and down-regulates VASCULAR ENDOTHELIAL GROWTH FACTOR expression through PI-3 KINASE and MAPK KINASES signaling pathways.
Substances that are recognized by the immune system and induce an immune reaction.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.
A major adhesion-associated heterodimer molecule expressed by MONOCYTES; GRANULOCYTES; NK CELLS; and some LYMPHOCYTES. The alpha subunit is the CD11C ANTIGEN, a surface antigen expressed on some myeloid cells. The beta subunit is the CD18 ANTIGEN.
A soluble factor produced by activated T-LYMPHOCYTES that induces the expression of MHC CLASS II GENES and FC RECEPTORS on B-LYMPHOCYTES and causes their proliferation and differentiation. It also acts on T-lymphocytes, MAST CELLS, and several other hematopoietic lineage cells.
Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A cytokine subunit that is a component of both interleukin-12 and interleukin-23. It binds to the INTERLEUKIN-12 SUBUNIT P35 via a disulfide bond to form interleukin-12 and to INTERLEUKIN-23 SUBUNIT P19 to form interleukin-23.
Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA).
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Multi-subunit proteins which function in IMMUNITY. They are produced by B LYMPHOCYTES from the IMMUNOGLOBULIN GENES. They are comprised of two heavy (IMMUNOGLOBULIN HEAVY CHAINS) and two light chains (IMMUNOGLOBULIN LIGHT CHAINS) with additional ancillary polypeptide chains depending on their isoforms. The variety of isoforms include monomeric or polymeric forms, and transmembrane forms (B-CELL ANTIGEN RECEPTORS) or secreted forms (ANTIBODIES). They are divided by the amino acid sequence of their heavy chains into five classes (IMMUNOGLOBULIN A; IMMUNOGLOBULIN D; IMMUNOGLOBULIN E; IMMUNOGLOBULIN G; IMMUNOGLOBULIN M) and various subclasses.
Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS.
Cell surface glycoproteins that bind to chemokines and thus mediate the migration of pro-inflammatory molecules. The receptors are members of the seven-transmembrane G protein-coupled receptor family. Like the CHEMOKINES themselves, the receptors can be divided into at least three structural branches: CR, CCR, and CXCR, according to variations in a shared cysteine motif.
A dioxygenase with specificity for the oxidation of the indoleamine ring of TRYPTOPHAN. It is an extrahepatic enzyme that plays a role in metabolism as the first and rate limiting enzyme in the kynurenine pathway of TRYPTOPHAN catabolism.
Bone marrow-derived lymphocytes that possess cytotoxic properties, classically directed against transformed and virus-infected cells. Unlike T CELLS; and B CELLS; NK CELLS are not antigen specific. The cytotoxicity of natural killer cells is determined by the collective signaling of an array of inhibitory and stimulatory CELL SURFACE RECEPTORS. A subset of T-LYMPHOCYTES referred to as NATURAL KILLER T CELLS shares some of the properties of this cell type.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Class of pro-inflammatory cytokines that have the ability to attract and activate leukocytes. They can be divided into at least three structural branches: C; (CHEMOKINES, C); CC; (CHEMOKINES, CC); and CXC; (CHEMOKINES, CXC); according to variations in a shared cysteine motif.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.
Group of chemokines with adjacent cysteines that are chemoattractants for lymphocytes, monocytes, eosinophils, basophils but not neutrophils.
A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA.
The engulfing and degradation of microorganisms; other cells that are dead, dying, or pathogenic; and foreign particles by phagocytic cells (PHAGOCYTES).
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Antigens on surfaces of cells, including infectious or foreign cells or viruses. They are usually protein-containing groups on cell membranes or walls and may be isolated.
Sarcoma of FOLLICULAR DENDRITIC CELLS most often found in the lymph nodes. This rare neoplasm occurs predominately in adults.
A CD antigen that contains a conserved I domain which is involved in ligand binding. When combined with CD18 the two subunits form MACROPHAGE-1 ANTIGEN.
An intracellular signaling adaptor protein that plays a role in TOLL-LIKE RECEPTOR and INTERLEUKIN 1 RECEPTORS signal transduction. It forms a signaling complex with the activated cell surface receptors and members of the IRAK KINASES.
Protection from an infectious disease agent that is mediated by B- and T- LYMPHOCYTES following exposure to specific antigen, and characterized by IMMUNOLOGIC MEMORY. It can result from either previous infection with that agent or vaccination (IMMUNITY, ACTIVE), or transfer of antibody or lymphocytes from an immune donor (IMMUNIZATION, PASSIVE).
Antigenic determinants recognized and bound by the T-cell receptor. Epitopes recognized by the T-cell receptor are often located in the inner, unexposed side of the antigen, and become accessible to the T-cell receptors after proteolytic processing of the antigen.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.
Manifestations of the immune response which are mediated by antigen-sensitized T-lymphocytes via lymphokines or direct cytotoxicity. This takes place in the absence of circulating antibody or where antibody plays a subordinate role.
Experimentally induced tumor that produces MELANIN in animals to provide a model for studying human MELANOMA.
Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.
Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.
Glycolipid-anchored membrane glycoproteins expressed on cells of the myelomonocyte lineage including monocytes, macrophages, and some granulocytes. They function as receptors for the complex of lipopolysaccharide (LPS) and LPS-binding protein.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.
Interferon inducer consisting of a synthetic, mismatched double-stranded RNA. The polymer is made of one strand each of polyinosinic acid and polycytidylic acid.
A type of acute or chronic skin reaction in which sensitivity is manifested by reactivity to materials or substances coming in contact with the skin. It may involve allergic or non-allergic mechanisms.
Mature LYMPHOCYTES and MONOCYTES transported by the blood to the body's extravascular space. They are morphologically distinguishable from mature granulocytic leukocytes by their large, non-lobed nuclei and lack of coarse, heavily stained cytoplasmic granules.
Specialized forms of antibody-producing B-LYMPHOCYTES. They synthesize and secrete immunoglobulin. They are found only in lymphoid organs and at sites of immune responses and normally do not circulate in the blood or lymph. (Rosen et al., Dictionary of Immunology, 1989, p169 & Abbas et al., Cellular and Molecular Immunology, 2d ed, p20)
A pattern recognition receptor that forms heterodimers with other TOLL-LIKE RECEPTORS. It interacts with multiple ligands including PEPTIDOGLYCAN, bacterial LIPOPROTEINS, lipoarabinomannan, and a variety of PORINS.
Membrane glycoproteins consisting of an alpha subunit and a BETA 2-MICROGLOBULIN beta subunit. In humans, highly polymorphic genes on CHROMOSOME 6 encode the alpha subunits of class I antigens and play an important role in determining the serological specificity of the surface antigen. Class I antigens are found on most nucleated cells and are generally detected by their reactivity with alloantisera. These antigens are recognized during GRAFT REJECTION and restrict cell-mediated lysis of virus-infected cells.
Established cell cultures that have the potential to propagate indefinitely.
A CC-type chemokine with specificity for CCR6 RECEPTORS. It has activity towards DENDRITIC CELLS; T-LYMPHOCYTES; and B-LYMPHOCYTES.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.
Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.
A pattern recognition receptor that recognizes GUANOSINE and URIDINE-rich single-stranded RNA.
A heterodimeric cytokine that plays a role in innate and adaptive immune responses. Interleukin-23 is comprised of a unique 19 kDa subunit and 40 kDa subunit that is shared with INTERLEUKIN-12. It is produced by DENDRITIC CELLS; MACROPHAGES and a variety of other immune cells
The altered state of immunologic responsiveness resulting from initial contact with antigen, which enables the individual to produce antibodies more rapidly and in greater quantity in response to secondary antigenic stimulus.
Antibodies produced by a single clone of cells.
Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Theoretical representations that simulate the behavior or activity of immune system, processes, or phenomena. They include the use of mathematical equations, computers, and other electrical equipment.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A group of three different alpha chains (CD11a, CD11b, CD11c) that are associated with an invariant CD18 beta chain (ANTIGENS, CD18). The three resulting leukocyte-adhesion molecules (RECEPTORS, LEUKOCYTE ADHESION) are LYMPHOCYTE FUNCTION-ASSOCIATED ANTIGEN-1; MACROPHAGE-1 ANTIGEN; and ANTIGEN, P150,95.
Deliberate stimulation of the host's immune response. ACTIVE IMMUNIZATION involves administration of ANTIGENS or IMMUNOLOGIC ADJUVANTS. PASSIVE IMMUNIZATION involves administration of IMMUNE SERA or LYMPHOCYTES or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow).
Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.
The number of CELLS of a specific kind, usually measured per unit volume or area of sample.
A rare sarcoma of INTERDIGITATING CELLS found in the lymph nodes and non-lymphoid organs. They exhibit a variable immunophenotype and lack Birbeck granules.
The movement of cells or organisms toward or away from a substance in response to its concentration gradient.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
Antigens that exist in alternative (allelic) forms in a single species. When an isoantigen is encountered by species members who lack it, an immune response is induced. Typical isoantigens are the BLOOD GROUP ANTIGENS.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
CCR receptors with specificity for CHEMOKINE CCL20. They are expressed at high levels in T-LYMPHOCYTES; B-LYMPHOCYTES; and DENDRITIC CELLS.
Subset of helper-effector T-lymphocytes which synthesize and secrete IL-17, IL-17F, and IL-22. These cytokines are involved in host defenses and tissue inflammation in autoimmune diseases.
One of the type I interferons produced by fibroblasts in response to stimulation by live or inactivated virus or by double-stranded RNA. It is a cytokine with antiviral, antiproliferative, and immunomodulating activity.
The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.
Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.
A melanosome-specific protein that plays a role in the expression, stability, trafficking, and processing of GP100 MELANOMA ANTIGEN, which is critical to the formation of Stage II MELANOSOMES. The protein is used as an antigen marker for MELANOMA cells.
The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.
A specific immune response elicited by a specific dose of an immunologically active substance or cell in an organism, tissue, or cell.
A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.
The body's defense mechanism against foreign organisms or substances and deviant native cells. It includes the humoral immune response and the cell-mediated response and consists of a complex of interrelated cellular, molecular, and genetic components.
A round-to-oval mass of lymphoid tissue embedded in the lateral wall of the PHARYNX. There is one on each side of the oropharynx in the fauces between the anterior and posterior pillars of the SOFT PALATE.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Specific molecular sites on the surface of various cells, including B-lymphocytes and macrophages, that combine with IMMUNOGLOBULIN Gs. Three subclasses exist: Fc gamma RI (the CD64 antigen, a low affinity receptor), Fc gamma RII (the CD32 antigen, a high affinity receptor), and Fc gamma RIII (the CD16 antigen, a low affinity receptor).
DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.
The endogenous compounds that mediate inflammation (AUTACOIDS) and related exogenous compounds including the synthetic prostaglandins (PROSTAGLANDINS, SYNTHETIC).
Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.
Active immunization where vaccine is administered for therapeutic or preventive purposes. This can include administration of immunopotentiating agents such as BCG vaccine and Corynebacterium parvum as well as biological response modifiers such as interferons, interleukins, and colony-stimulating factors in order to directly stimulate the immune system.
An inhibitory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 PROTEIN. CD274 antigen provides negative signals that control and inhibit T-cell responses and is found at higher than normal levels on tumor cells, suggesting its potential role in TUMOR IMMUNE EVASION.
A specific HLA-A surface antigen subtype. Members of this subtype contain alpha chains that are encoded by the HLA-A*02 allele family.
A CC-type chemokine with specificity for CCR4 RECEPTORS. It has activity towards TH2 CELLS and TC2 CELLS.
A cell line derived from cultured tumor cells.
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
Lymphoid tissue on the mucosa of the small intestine.
The activated center of a lymphoid follicle in secondary lymphoid tissue where B-LYMPHOCYTES are stimulated by antigens and helper T cells (T-LYMPHOCYTES, HELPER-INDUCER) are stimulated to generate memory cells.
Nonsusceptibility to the invasive or pathogenic effects of foreign microorganisms or to the toxic effect of antigenic substances.
A cytokine that stimulates the growth and differentiation of B-LYMPHOCYTES and is also a growth factor for HYBRIDOMAS and plasmacytomas. It is produced by many different cells including T-LYMPHOCYTES; MONOCYTES; and FIBROBLASTS.
The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a GENE TRANSFER TECHNIQUE.
Biologically active substances whose activities affect or play a role in the functioning of the immune system.
Nonsusceptibility to the pathogenic effects of foreign microorganisms or antigenic substances as a result of antibody secretions of the mucous membranes. Mucosal epithelia in the gastrointestinal, respiratory, and reproductive tracts produce a form of IgA (IMMUNOGLOBULIN A, SECRETORY) that serves to protect these ports of entry into the body.
The cells found in the body fluid circulating throughout the CARDIOVASCULAR SYSTEM.
Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA.
A proinflammatory cytokine produced primarily by T-LYMPHOCYTES or their precursors. Several subtypes of interleukin-17 have been identified, each of which is a product of a unique gene.
A subunit of interleukin-12. It binds to the INTERLEUKIN-12 SUBUNIT P40 via a disulfide bond that results in the active cytokine.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
The engulfing of liquids by cells by a process of invagination and closure of the cell membrane to form fluid-filled vacuoles.
Progenitor cells from which all blood cells derive.
Methods for maintaining or growing CELLS in vitro.
Glycoproteins found on immature hematopoietic cells and endothelial cells. They are the only molecules to date whose expression within the blood system is restricted to a small number of progenitor cells in the bone marrow.
Soluble factors which stimulate growth-related activities of leukocytes as well as other cell types. They enhance cell proliferation and differentiation, DNA synthesis, secretion of other biologically active molecules and responses to immune and inflammatory stimuli.
A subclass of winged helix DNA-binding proteins that share homology with their founding member fork head protein, Drosophila.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
Fluorescent probe capable of being conjugated to tissue and proteins. It is used as a label in fluorescent antibody staining procedures as well as protein- and amino acid-binding techniques.
A pattern recognition receptor that binds DOUBLE-STRANDED RNA. It mediates cellular responses to certain viral pathogens.
A melanosome-associated protein that plays a role in the maturation of the MELANOSOME.
Alteration of the immune system or of an immune response by agents that activate or suppress its function. This can include IMMUNIZATION or administration of immunomodulatory drugs. Immunomodulation can also encompass non-therapeutic alteration of the immune system effected by endogenous or exogenous substances.
A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)
Antigen-type substances that produce immediate hypersensitivity (HYPERSENSITIVITY, IMMEDIATE).
A subunit of interleukin-23. It combines with INTERLEUKIN-12 SUBUNIT P40, which is shared between the two cytokines, to form in the active interleukin-23 cytokine.
Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa), antigenic proteins, synthetic constructs, or other bio-molecular derivatives, administered for the prevention, amelioration, or treatment of infectious and other diseases.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.
High affinity receptors for INTERLEUKIN-3. They are found on early HEMATOPOIETIC PROGENITOR CELLS; progenitors of MYELOID CELLS; EOSINOPHILS; and BASOPHILS. Interleukin-3 receptors are formed by the dimerization of the INTERLEUKIN-3 RECEPTOR ALPHA SUBUNIT and the CYTOKINE RECEPTOR COMMON BETA SUBUNIT.
Cerebrosides which contain as their polar head group a galactose moiety bound in glycosidic linkage to the hydroxyl group of ceramide. Their accumulation in tissue, due to a defect in beta-galactosidase, is the cause of galactosylceramide lipidosis or globoid cell leukodystrophy.
A membrane-bound tumor necrosis family member that is expressed on activated antigen-presenting cells such as B-LYMPHOCYTES and MACROPHAGES. It signals T-LYMPHOCYTES by binding the OX40 RECEPTOR.
A costimulatory B7 antigen that has specificity for the T-CELL receptor PROGRAMMED CELL DEATH 1 RECEPTOR. It is closely-related to CD274 antigen; however, its expression is restricted to DENDRITIC CELLS and activated MACROPHAGES.
The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.
Distinctive neoplastic disorders of histiocytes. Included are malignant neoplasms of MACROPHAGES and DENDRITIC CELLS.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
The forcing into the skin of liquid medication, nutrient, or other fluid through a hollow needle, piercing the top skin layer.
Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin.

Reciprocal control of T helper cell and dendritic cell differentiation. (1/14470)

It is not known whether subsets of dendritic cells provide different cytokine microenvironments that determine the differentiation of either type-1 T helper (TH1) or TH2 cells. Human monocyte (pDC1)-derived dendritic cells (DC1) were found to induce TH1 differentiation, whereas dendritic cells (DC2) derived from CD4+CD3-CD11c- plasmacytoid cells (pDC2) induced TH2 differentiation by use of a mechanism unaffected by interleukin-4 (IL-4) or IL-12. The TH2 cytokine IL-4 enhanced DC1 maturation and killed pDC2, an effect potentiated by IL-10 but blocked by CD40 ligand and interferon-gamma. Thus, a negative feedback loop from the mature T helper cells may selectively inhibit prolonged TH1 or TH2 responses by regulating survival of the appropriate dendritic cell subset.  (+info)

Potent immunoregulatory effects of Salmonella typhi flagella on antigenic stimulation of human peripheral blood mononuclear cells. (2/14470)

A key function of monocytes/macrophages (Mphi) is to present antigens to T cells. However, upon interaction with bacteria, Mphi lose their ability to effectively present soluble antigens. This functional loss was associated with alterations in the expression of adhesion molecules and CD14 and a reduction in the uptake of soluble antigen. Recently, we have demonstrated that Salmonella typhi flagella (STF) markedly decrease CD14 expression and are potent inducers of proinflammatory cytokine production by human peripheral blood mononuclear cells (hPBMC). In order to determine whether S. typhi and soluble STF also alter the ability of Mphi to activate T cells to proliferate to antigens and mitogens, hPBMC were cultured in the presence of tetanus toxoid (TT) or phytohemagglutinin (PHA) and either killed whole-cell S. typhi or purified STF protein. Both whole-cell S. typhi and STF suppressed proliferation to PHA and TT. This decreased proliferation was not a result of increased Mphi production of nitric oxide, prostaglandin E2, or oxygen radicals or the release of interleukin-1beta, tumor necrosis factor alpha, interleukin-6, or interleukin-10 following exposure to STF. However, the ability to take up soluble antigen, as determined by fluorescein isothiocyanate-labeled dextran uptake, was reduced in cells cultured with STF. Moreover, there was a dramatic reduction in the expression of CD54 on Mphi after exposure to STF. These results indicate that whole-cell S. typhi and STF have the ability to alter in vitro proliferation to soluble antigens and mitogens by affecting Mphi function.  (+info)

Disproportionate recruitment of CD8+ T cells into the central nervous system by professional antigen-presenting cells. (3/14470)

Inappropriate immune responses, thought to exacerbate or even to initiate several types of central nervous system (CNS) neuropathology, could arise from failures by either the CNS or the immune system. The extent that the inappropriate appearance of antigen-presenting cell (APC) function contributes to CNS inflammation and pathology is still under debate. Therefore, we characterized the response initiated when professional APCs (dendritic cells) presenting non-CNS antigens were injected into the CNS. These dendritic cells expressed numerous T-cell chemokines, but only in the presence of antigen did leukocytes accumulate in the ventricles, meninges, sub-arachnoid spaces, and injection site. Within the CNS parenchyma, the injected dendritic cells migrated preferentially into the white matter tracts, yet only a small percentage of the recruited leukocytes entered the CNS parenchyma, and then only in the white matter tracts. Although T-cell recruitment was antigen specific and thus mediated by CD4+ T cells in the models used here, CD8+ T cells accumulated in numbers equal to or greater than that of CD4+ T cells. Few of the recruited T cells expressed activation markers (CD25 and VLA-4), and those that did were primarily in the meninges, injection site, ventricles, and perivascular spaces but not in the parenchyma. These results indicate that 1) the CNS modulates the cellular composition and activation states of responding T-cell populations and that 2) myelin-restricted inflammation need not be initiated by a myelin-specific antigen.  (+info)

Bone marrow and peripheral blood dendritic cells from patients with multiple myeloma are phenotypically and functionally normal despite the detection of Kaposi's sarcoma herpesvirus gene sequences. (4/14470)

Multiple myeloma (MM) cells express idiotypic proteins and other tumor-associated antigens which make them ideal targets for novel immunotherapeutic approaches. However, recent reports show the presence of Kaposi's sarcoma herpesvirus (KSHV) gene sequences in bone marrow dendritic cells (BMDCs) in MM, raising concerns regarding their antigen-presenting cell (APC) function. In the present study, we sought to identify the ideal source of DCs from MM patients for use in vaccination approaches. We compared the relative frequency, phenotype, and function of BMDCs or peripheral blood dendritic cells (PBDCs) from MM patients versus normal donors. DCs were derived by culture of mononuclear cells in the presence of granulocyte-macrophage colony-stimulating factor and interleukin-4. The yield as well as the pattern and intensity of Ag (HLA-DR, CD40, CD54, CD80, and CD86) expression were equivalent on DCs from BM or PB of MM patients versus normal donors. Comparison of PBDCs versus BMDCs showed higher surface expression of HLA-DR (P =.01), CD86 (P =. 0003), and CD14 (P =.04) on PBDCs. APC function, assessed using an allogeneic mixed lymphocyte reaction (MLR), demonstrated equivalent T-cell proliferation triggered by MM versus normal DCs. Moreover, no differences in APC function were noted in BMDCs compared with PBDCs. Polymerase chain reaction (PCR) analysis of genomic DNA from both MM patient and normal donor DCs for the 233-bp KSHV gene sequence (KS330233) was negative, but nested PCR to yield a final product of 186 bp internal to KS330233 was positive in 16 of 18 (88.8%) MM BMDCs, 3 of 8 (37.5%) normal BMDCs, 1 of 5 (20%) MM PBDCs, and 2 of 6 (33.3%) normal donor PBDCs. Sequencing of 4 MM patient PCR products showed 96% to 98% homology to the published KSHV gene sequence, with patient specific mutations ruling out PCR artifacts or contamination. In addition, KHSV-specific viral cyclin D (open reading frame [ORF] 72) was amplified in 2 of 5 MM BMDCs, with sequencing of the ORF 72 amplicon revealing 91% and 92% homology to the KSHV viral cyclin D sequence. These sequences again demonstrated patient specific mutations, ruling out contamination. Therefore, our studies show that PB appears to be the preferred source of DCs for use in vaccination strategies due to the ready accessibility and phenotypic profile of PBDCs, as well as the comparable APC function and lower detection rate of KSHV gene sequences compared with BMDCs. Whether active KSHV infection is present and important in the pathophysiology of MM remains unclear; however, our study shows that MMDCs remain functional despite the detection of KSHV gene sequences.  (+info)

Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8(+) T cells resulting in a failure to lyse tumor cells. (5/14470)

Dendritic cells (DC) are critically involved in the initiation of primary immune processes, including tumor rejection. In our study, we investigated the effect of interleukin-10 (IL-10)-treated human DC on the properties of CD8(+) T cells that are known to be essential for the destruction of tumor cells. We show that IL-10-pretreatment of DC not only reduces their allostimulatory capacity, but also induces a state of alloantigen-specific anergy in both primed and naive (CD45RA+) CD8(+) T cells. To investigate the influence of IL-10-treated DC on melanoma-associated antigen-specific T cells, we generated a tyrosinase-specific CD8(+) T-cell line by several rounds of stimulation with the specific antigen. After coculture with IL-10-treated DC, restimulation of the T-cell line with untreated, antigen-pulsed DC demonstrated peptide-specific anergy in the tyrosinase-specific T cells. Addition of IL-2 to the anergic T cells reversed the state of both alloantigen- or peptide-specific anergy. In contrast to optimally stimulated CD8(+) T cells, anergic tyrosinase-specific CD8(+) T cells, after coculture with peptide-pulsed IL-10-treated DC, failed to lyse an HLA-A2-positive and tyrosinase-expressing melanoma cell line. Thus, our data demonstrate that IL-10-treated DC induce an antigen-specific anergy in cytotoxic CD8(+) T cells, a process that might be a mechanism of tumors to inhibit immune surveillance by converting DC into tolerogenic antigen-presenting cells.  (+info)

Presentation of renal tumor antigens by human dendritic cells activates tumor-infiltrating lymphocytes against autologous tumor: implications for live kidney cancer vaccines. (6/14470)

The clinical impact of dendritic cells (DCs) in the treatment of human cancer depends on their unique role as the most potent antigen-presenting cells that are capable of priming an antitumor T-cell response. Here, we demonstrate that functional DCs can be generated from peripheral blood of patients with metastatic renal cell carcinoma (RCC) by culture of monocytes/macrophages (CD14+) in autologous serum containing medium (RPMI) in the presence of granulocyte macrophage colony-stimulating factor and interleukin (IL) 4. For testing the capability of RCC-antigen uptake and processing, we loaded these DCs with autologous tumor lysate (TuLy) using liposomes, after which cytometric analysis of the DCs revealed a markedly increased expression of HLA class I antigen and a persistent high expression of class II. The immunogenicity of DC-TuLy was further tested in cultures of renal tumor infiltrating lymphocytes (TILs) cultured in low-dose IL-2 (20 Biologic Response Modifier Program units/ml). A synergistic effect of DC-TuLy and IL-2 in stimulating a T cell-dependent immune response was demonstrated by: (a) the increase of growth expansion of TILs (9.4-14.3-fold; day 21); (b) the up-regulation of the CD3+ CD56- TcR+ (both CD4+ and CD8+) cell population; (c) the augmentation of T cell-restricted autologous tumor lysis; and (d) the enhancement of IFN-gamma, tumor necrosis factor-alpha, granulocyte macrophage colony-stimulating factor, and IL-6 mRNA expression by TILs. Taken together, these data implicate that DC-TuLy can activate immunosuppressed TIL via an induction of enhanced antitumor CTL responses associated with production of Thl cells. This indicates a potential role of DC-TuLy vaccines for induction of active immunity in patients with advanced RCC.  (+info)

Identification of MAGE-3 epitopes presented by HLA-DR molecules to CD4(+) T lymphocytes. (7/14470)

MAGE-type genes are expressed by many tumors of different histological types and not by normal cells, except for male germline cells, which do not express major histocompatibility complex (MHC) molecules. Therefore, the antigens encoded by MAGE-type genes are strictly tumor specific and common to many tumors. We describe here the identification of the first MAGE-encoded epitopes presented by histocompatibility leukocyte antigen (HLA) class II molecules to CD4(+) T lymphocytes. Monocyte-derived dendritic cells were loaded with a MAGE-3 recombinant protein and used to stimulate autologous CD4(+) T cells. We isolated CD4(+) T cell clones that recognized two different MAGE-3 epitopes, MAGE-3114-127 and MAGE-3121-134, both presented by the HLA-DR13 molecule, which is expressed in 20% of Caucasians. The second epitope is also encoded by MAGE-1, -2, and -6. Our procedure should be applicable to other proteins for the identification of new tumor-specific antigens presented by HLA class II molecules. The knowledge of such antigens will be useful for evaluation of the immune response of cancer patients immunized with proteins or with recombinant viruses carrying entire genes coding for tumor antigens. The use of antigenic peptides presented by class II in addition to peptides presented by class I may also improve the efficacy of therapeutic antitumor vaccination.  (+info)

Maturation, activation, and protection of dendritic cells induced by double-stranded RNA. (8/14470)

The initiation of an immune response is critically dependent on the activation of dendritic cells (DCs). This process is triggered by surface receptors specific for inflammatory cytokines or for conserved patterns characteristic of infectious agents. Here we show that human DCs are activated by influenza virus infection and by double-stranded (ds)RNA. This activation results not only in increased antigen presentation and T cell stimulatory capacity, but also in resistance to the cytopathic effect of the virus, mediated by the production of type I interferon, and upregulation of MxA. Because dsRNA stimulates both maturation and resistance, DCs can serve as altruistic antigen-presenting cells capable of sustaining viral antigen production while acquiring the capacity to trigger naive T cells and drive polarized T helper cell type 1 responses.  (+info)

Background: Dendritic cells (DCs) are professional antigen presenting cells that have an important role in the initiation of immune response. The use of maturation factors in dendritic cell differentiation provides a promising approach in immunotherapy. Objective: In this study, we compared tumor necrosis factor-α, polyribocytidylic acid, lipopolysacharide and CpG oligonucleotides in inducing dendritic cell maturation. Methods: We generated immature dendritic cells with GM-CSF in combination with IL-4 from peripheral blood mononuclear adherent cells and used tumor necrosis factor-α, polyribocytidylic acid, lipopolysacharide and CpG for the induction of dendritic cell maturation. CD83 maturation marker on the dendritic cells was analyzed by flowcytometry after 7 days. In addition, mixed leukocyte reaction between dendritic cells and T cells was performed by MTT proliferation assay. Results: Flow cytometry results demonstrated a comparable high level of CD83 expression on the mature dendritic cells
Objective: Sjögrens syndrome (SS) is a lymphoproliferative autoimmune disease, characterized by dryness of the mouth and eyes. Dendritic cells (DC) are potent antigen-presenting cells and crucial for initiating and maintaining primary immune responses. Here, we quantified interferon producing plasmacytoid DC (pDC) and two myeloid DC subsets (mDC1 and mDC2) in human peripheral blood from primary SS (pSS) patients and healthy controls in order to investigate whether alterations among DC subsets play a potential role in the disease. Method: Blood samples from 31 pSS patients and 28 gender- and age-matched healthy controls were analyzed by flow cytometry using the Miltenyi Blood DC Enumeration kit. The presence of pDC in salivary glands (SG) from pSS patients was analyzed by immunohistochemistry. Results: Patients with pSS had significantly less pDC and mDC2 in peripheral blood compared to healthy controls. Moreover, pDC are present in SG from patients with pSS. Conclusion: Alterations among DC ...
Dendritic cell-based immunotherapy employs the patients immune system to fight neoplastic lesions spread over the entire body. This makes it an important therapy option for patients suffering from metastatic melanoma, which is often resistant to chemotherapy. However, conventional cellular vaccination approaches, based on monocyte-derived dendritic cells, only achieved modest response rates despite continued optimization of various vaccination parameters. In addition, the generation of monocyte-derived dendritic cells requires extensive ex vivo culture conceivably hampering the immunogenicity of the vaccine. Recent studies, thus, focused on vaccines that make use of primary dendritic cells. Though rare in the blood, these naturally circulating dendritic cells can be readily isolated and activated thereby circumventing lengthy ex vivo culture periods. The first clinical trials not only showed increased survival rates but also the induction of diversified anticancer immune responses. Upcoming treatment
Background: Dendritic cells (DCs) are professional antigen-presenting cells able to induce immunity or tolerance. The interactions of immature DCs with naive T lymphocytes induce peripheral tolerance through mechanisms that include anergy or deletion of lymphocytes or the generation of regulatory T cells. Because of the central role of DCs in the immune response, they are potential targets for the induction of experimental tolerance. Thus, the generation of immature (tolerogenic) DCs able to capture and present alloantigens to T cells represents an important aim in our efforts to achieve better transplant acceptance. Methods: In this work, we generated immature DCs by using vitamin D 3 (VD3) during the process of DC differentiation. Results: The VD3DCs showed an immature phenotype characterized by a low expression of major histocompatibility complex antigens of class II, CD86, and CD80 molecules and the secretion of a tolerogenic cytokine pattern. Furthermore, we showed that VD3DCs ...
Dendritic Cell Vaccines have been around for over 20 years but early results suggested they had an effect in only 12% of brain cancer patients; but now in a new 4 country clinical trial, Dendritic Cell Vaccine (DCVax -L) seems to give some patients over 7 years of extra survival, fulfilling the early promise of this form of immunotherapy for brain tumours.. Using Temozolomide with Dendritic Cell Vaccine ((DCVax ® -L). For patients with GBM, standard treatment involves surgery, radiotherapy and temozolomide. Here, the researchers announced results of their Phase III trial where an autologous tumour-lysate-pulsed Dendritic Cell Vaccine ((DCVax ® -L) was added to the standard programme.. In this study patients after surgery received either Temozolomide plus the vaccine, or Temozolomide plus a placebo.. However, where recurrence occurred all patients were allowed to have the Dendritic Cell vaccine.. The Intention to Treat (ITT) mean Overall Survival time was shown to be 23.3 months from ...
Dendritic cells (DCs) are potent antigen-presenting cells endowed with the unique ability to initiate adaptive immune responses upon inflammation. Inflammatory processes are often associated with an increased production of serotonin, which operates by activating specific receptors. However, the functional role of serotonin receptors in regulation of DC functions is poorly understood. Here we demonstrate that expression of serotonin receptor 5-HT7 (5-HT7R) as well as its down-stream effector Cdc42 is upregulated in DCs upon maturation. While DC maturation was independent of 5-HT7R, receptor stimulation affected DC morphology via Cdc42-mediated signaling. In addition, basal activity of 5-HT7R was required for the proper expression of the chemokine receptor CCR7, which is a key factor to control DC migration. Consistently, we observed that 5-HT7R enhances chemotactic motility of DCs in vitro by modulating their directionality and migration velocity. Accordingly, migration of DCs in murine colon ...
Dendritic cells (DCs) are professional antigen-presenting cells of the immune system with the ability to induce and control T and B cells responses. Monocytes have been used as precursors to generate DC vaccines ex vivo. Monocyte-derived DCs have been used as vaccines in clinical trials to treat cancer and infectious disease by eliciting potent T cell responses. Infection with Human Immunodeficiency Virus (HIV) almost invariably leads to a chronic disease. Eventually the destruction of the immune system culminates into Acquired Immune Deficiency Syndrome (AIDS). Since the advent of Highly Active Antiretroviral Therapy (HAART), HIV patients have been able to control viral levels. However, with prolonged use of treatment, these patients experience serious adverse effects such as liver and mitochondrial toxicity that can potentially become fatal. Long-Term Non-Progressors (LTNP) are a unique subpopulation of HIV patients that are able to control their viral load without HAART. Studies revealed ...
The recognition and eradication of cancer cells by the immune system is reliant on dendritic cells (DCs). DCs are professional antigen-presenting cells (APCs) that are integral for the initiation of an adaptive immune response targeted to eliminate cancer cells. DCs are capable of cross-presentation, a necessary function for priming of cytotoxic T lymphocyte (CTL) responses. Specialised DC subsets are reported to be superior at cross-presenting and have been implicated as crucial cells for CTL responses against tumour progression. However, DCs are often inactive in the presence of immune-suppressive tumours and require stimulation to become activated. Immunotherapy can be utilised to provide stimulatory factors that drive the activation of DCs and subsequent initiation of effective anti-tumour responses. The immunotherapies investigated in this thesis were poly I:C, a toll-like receptor (TLR) 3 ligand; and combination of the danger signal monosodium urate crystals (MSU) and a Mycobacterium ...
Dendritic cells (DCs) are potent antigen-presenting cells that initiate protective T-cell immunity in mice. To study the immunogenicity of DCs in humans, we injected 9 healthy subjects subcutaneously with a control injection of autologous monocyte-derived, mature DCs, followed 4-6 weeks later by DCs pulsed with keyhole limpet hemocyanin (KLH), HLA-A*0201-positive restricted influenza matrix peptide (MP), and tetanus toxoid (TT). Four more subjects received these antigens without DCs. Injection of unpulsed DCs, or antigens alone, failed to immunize. Priming of CD4(+) T cells to KLH was observed in all 9 subjects injected with KLH-pulsed DCs, and boosting of TT-specific T-cell immunity was seen in 5 of 6 subjects injected with TT-pulsed DCs. Injection of antigen-pulsed DCs led to a severalfold increase in freshly isolated MP-specific, IFN-gamma-secreting CD8(+) T cells in all 6 HLA-A*0201-positive subjects, as early as 7 days after injection. When T cells were boosted in culture, there was an increase in
Cell surface markers of mouse thymic dendritic cells have been studied by flow cytometry after isolation by collagenase digestion, separation of the low-density cell fraction and differential adherence. The dendritic cell preparation had a purity of , 90%, the contaminating population being essentially composed of thymocytes, macrophages constituting ,1%. Dendritic cells displayed high forward and low-intermediate side angle scatter, and expressed high levels of major histocompatibility complex (MHC) class I and class II molecules, the heat-stable antigen (HSA), the adhesion molecules Pgp-1 (CD44), LFA-1, ICAM-1 and low levels of Mac-1 and the leukocyte common antigen CD45. Thymic dendritic cells are negative for the stem cell antigen-2 (Sca-2), the B cell-specific form of CD45 (B220), the mouse macrophage markers Fc receptor and F4/80, and the granulocyte marker Gr-1. However, although they do not express the T cell markers Thy-1, CD2, CD3, CD4 and CD5, 20%-30% of dendritic cells are positive ...
Myeloid dendritic cells (DCs) are professional antigen-presenting cells critical for the orchestration of immunity and maintenance of self-tolerance. DC development and functions are tightly regulated by
TY - JOUR. T1 - Functional redundancy between thymic CD8α+and Sirpα+ conventional dendritic cells in presentation of blood-derived lysozyme by MHC class II proteins. AU - Atibalentja, Danielle F.. AU - Murphy, Kenneth M.. AU - Unanue, Emil R.. PY - 2011/2/1. Y1 - 2011/2/1. N2 - We evaluated the presentation of blood-derived protein Ags by APCs in the thymus. Two conventional dendritic cells (cDCs), the CD8α +Sirpa-CD11chi (CD8α+ cDC) and the CD8α-Sirpα+CD11chi (Sirpa + cDC), were previously identified as presenting MHC class II bound peptides from hen egg white lysozyme (HEL) injected intravenously. All thymic APCs acquired the injected HEL, with the plasmacytoid dendritic cell being the best, followed by the Sirpα+ cDC and the CD8α+ cDC. Both cDCs induced to similar extent negative selection and regulatory T cells in HEL TCR transgenic mice, indicating a redundant role of the two cDC subsets in the presentation of blood-borne HEL. Immature dendritic cells or plasmacytoid dendritic cells ...
1. ShortmanK. LiuYJ. 2002. Mouse and human dendritic cell subtypes.. Nat Rev Immunol. 2. 151. 161. 2. AlmeidaM. CorderoM. AlmeidaJ. OrfaoA. 2005. Different subsets of peripheral blood dendritic cells show distinct phenotypic and functional abnormalities in HIV-1 infection.. AIDS. 19. 261. 271. 3. BarronMA. BlyveisN. PalmerBE. MaWhinneyS. WilsonCC. 2003. Influence of plasma viremia on defects in number and immunophenotype of blood dendritic cell subsets in human immunodeficiency virus 1-infected individuals.. J Infect Dis. 187. 26. 37. 4. DonaghyH. PozniakA. GazzardB. QaziN. GilmourJ. 2001. Loss of blood CD11c(+) myeloid and CD11c(−) plasmacytoid dendritic cells in patients with HIV-1 infection correlates with HIV-1 RNA virus load.. Blood. 98. 2574. 2576. 5. GrassiF. HosmalinA. McIlroyD. CalvezV. DebreP. 1999. Depletion in blood CD11c-positive dendritic cells from HIV-infected patients.. AIDS. 13. 759. 766. 6. PacanowskiJ. KahiS. BailletM. LebonP. DeveauC. 2001. Reduced blood CD123+ (lymphoid) ...
1. Banchereau J, Steinman R.M. Dendritic cells and the control of immunity. Nature. 1998;392(6673):245-52 2. Zitvogel L. Dendritic and natural killer cells cooperate in the control/switch of innate immunity. J Exp Med. 2002;195(3):F9-14 3. Banchereau J. et al. Immunobiology of dendritic cells. Annu Rev Immunol. 2000;18:767-811 4. Lanzavecchia A, Sallusto F. Regulation of T cell immunity by dendritic cells. Cell. 2001;106(3):263-6 5. Garg S. et al. Genetic tagging shows increased frequency and longevity of antigen-presenting, skin-derived dendritic cells in vivo. Nat Immunol. 2003;4(9):907-12 6. Mellman I, Steinman R.M. Dendritic cells: specialized and regulated antigen processing machines. Cell. 2001;106(3):255-8 7. Zhang Z. et al. Differential restoration of myeloid and plasmacytoid dendritic cells in HIV-1-infected children after treatment with highly active antiretroviral therapy. Immunol J. 2006;176(9):5644-51 8. Allan R.S. et al. Epidermal viral immunity induced by CD8alpha+ dendritic cells ...
TY - JOUR. T1 - Human peripheral blood dendritic cells and monocyte subsets display similar chemokine receptor expression profiles with differential migratory responses. AU - Cravens, P. D.. AU - Hayashida, K.. AU - Davis, L. S.. AU - Nanki, T.. AU - Lipsky, P. E.. PY - 2007/6. Y1 - 2007/6. N2 - Human antigen presenting cells (APC) found in peripheral blood are considered to be precursors that have been released from the bone marrow and are in transit to the peripheral tissues. These APC populations include myeloid dendritic cells (mDC), plasmacytoid DC (pDC) and monocytes (Mo). To assign specialized functional roles and stages of development for APCs, CD33 expressing APC subsets were examined for their capacity to respond to chemokines. Three major CD33+ subsets including CD33brightCD14 bright Mo, CD33brightCD14- CD11c+ mDC and CD33dimCD14- pDC were present. Dendritic cells subsets and Mo expressed low levels of CC and CXC receptors, but distinctive chemokine receptor expression profiles were ...
CYTIP (cytohesin interacting protein) is an intracellular molecule induced in dendritic cells during maturation. CYTIP modulates the binding intensity of the adhesion molecule LFA-1. If dendritic cells are silenced for CYTIP they keep longer contacts with T-cells resulting in a lower T cell stimulation. We identified Suppressor of cytokine signaling-1 (SOCS-1) as a binding partner for CYTIP in human monocyte derived dendritic cells. In Western blot analyses we found that CYTIP expression is down regulated at later time points, starting at about 72 hours after induction of maturation. To investigate a possible role for SOCS-1 in taking CYTIP to the degradation machinery of the cell we measured endogenous CYTIP protein levels in mature dendritic cells transfected with SOCS-1 encoding plasmid in quantitative Western blot analyses. We observed lower amounts of endogenous CYTIP in mature dendritic cells transfected with SOCS-1 encoding plasmid compared with untransfected dendritic cells. Experiments with the
TY - JOUR. T1 - Morphine inhibits murine dendritic cell IL-23 production by modulating toll-like receptor 2 and Nod2 signaling. AU - Wang, Jinghua. AU - Ma, Jing. AU - Charboneau, Rick. AU - Barke, Roderick. AU - Roy, Sabita. PY - 2011/3/25. Y1 - 2011/3/25. N2 - IL-23, produced by dendritic cells (DCs) and macrophages, plays a critical role in innate immunity against bacterial infection. Our previous studies show that morphine disrupts the IL-23/IL-17 mediated pulmonary mucosal host defense and increases susceptibility to Streptococcus pneumoniae lung infection. To determine the mechanism by which morphine modulates IL-23 production, mouse bone marrow-derived dendritic cells (BMDCs) and macrophages (BMDMs) were treated with morphine, and infected with S. pneumoniae or stimulated with Toll-like receptor (TLR) and Nod2 ligands. We found that a significant increase in IL-23 protein production was observed in S. pneumoniae, TLR2 ligand lipoteichoic acid (LTA), and TLR4 ligand pneumolysin (PLY) ...
This study is being done to see if the investigators can help the immune system to work against melanoma.. A dendritic cell is another type of white blood cell. It has most, if not all, of the proteins needed to make T cells work to destroy cancer cells. However, dendritic cells do not normally have the cancer proteins on their surface. The challenge then is to combine the antigens with dendritic cells to make a vaccine. The investigators think that the bodys T cells might then react against the tumor and help destroy it.. This study will see if altered dendritic cells will make T cells work against tumor cells. The dendritic cells will be made in a lab and will carry the antigens. These cells then will be injected under the skin.. In this study, the investigators are trying to help the body make a stronger immune response against the cancer. The patient will get the same kind of dendritic cell vaccine used in the earlier study, but with one major difference. The dendritic cells will contain ...
Results In their resting state the monocyte derived dendritic cells expressed MHC class II, but very low levels of co-stimulatory molecules CD80, CD83 and CD86. Upon culture with H. pylori, the cells expressed significantly higher levels of these co-stimulatory molecules, demonstrating maturation (,25 fold increase in percentage of positive events for CD80, CD83, CD86 on flow cytometry; p,0.01). There were no differences between the responses to wild type and dupA knockout mutant strains, or following stimulation with lipopolysaccharide (LPS). The H. pylori-matured dendritic cells secreted high levels of IL-12p40, IL-12p70, IL-10 and IL-23. The concentrations induced by the dupA+ strains were significantly higher than those induced by the dupA mutants (1.5 fold increase in IL-12p40 production, p,0.05; 1.4 fold increase in IL-12p70, p,0.05).. ...
Chang S-Y, Song J-H, Guleng B, Cotoner CA, Arihiro S, Zhao Y, Chiang H-S, OKeeffe M, Liao G, Karp CL, et al. Circulatory antigen processing by mucosal dendritic cells controls CD8(+) T cell activation. Immunity. 2013;38 (1) :153-65.
Dendritic cells, particularly those residing in the spleen, are thought to orchestrate acquired immunity to malaria, but it is not known how the splenic dendritic cell population responds to malaria infection and how this response compares with the responses of other antigen-presenting cells. We investigated this question for Plasmodium chabaudi AS infection in C57BL/6 mice. We found that dendritic cells, defined here by the CD11c marker, migrated from the marginal zone of the spleen into the CD4(+) T-cell area within 5 days after parasites entered the bloodstream. This contrasted with the results observed for the macrophage and B-cell populations, which expanded greatly but did not show any comparable migration. Over the same time period dendritic cells showed upregulation of CD40, CD54, and CD86 costimulatory molecules that are required for successful T-cell activation. In dendritic cells, the peak intracellular gamma interferon expression (as shown by fluorescence-activated cell sorting) was on day 5
Tumor-infiltrating dendritic cell subsets of progressive or regressive tumors induce suppressive or protective immune responses. - Yongqing Liu, Xuguang Bi, Shulin Xu, Jim Xiang
Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here, we combine two high-dimensional technologies-s …
Dendritic cells represent important components of the innate and adaptive immune responses. Human dendritic cells can be divided into two major subsets: myeloid and plasmacytoid (lymphoid) dendritic cells. The unique function of the dendritic cells is to capture antigens, present and to activate the antigenic peptides to the T lymphocytes. Dendritic cells go through a maturation process both in vitro and in vivo. By the use of pathogenrecognition- receptors the immature dendritic cells sense diverse pathogens or their various components, or cellular factors produced by the infected neighboring non-dendritic cells, and maturation signals are transduced for the dendritic cells. The heterogeneity of the pathogen-recognition-receptors and the microbial stimuli initiate a broad range of interactions between dendritic cells and infectious agents. Dendritic cells infected with certain viruses produce only a few infectious particles, but express and present viral antigens to T lymphocytes and immune ...
Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that play a critical role in the induction of antitumor immunity. Therefore, various strategies have been developed to deliver tumor-associated antigens (TAAs) to DCs as cancer vaccines. The fusion of DCs and whole tumor cells to generate DC-tumor fusion cells (DC-tumor FCs) is an alternative strategy to treat cancer patients. The cell fusion method allows DCs to be exposed to the broad array of TAAs originally expressed by whole tumor cells. DCs then process TAAs endogenously and present them through major histocompatibility complex (MHC) class I and II pathways in the context of costimulatory molecules, resulting in simultaneous activation of both CD4+ and CD8+ T cells. DC-tumor FCs require optimized enhanced immunogenicity of both DCs and whole tumor cells. In this context, an effective fusion strategy also needs to produce immunogenic DC-tumor FCs. We discuss the potential ability of DC-tumor FCs and the recent progress in improving
4717 A lipoteichoic acid-related molecule OK-PSA is an active component of OK-432, a Streptococcus-derived anti-cancer immunotherapeutic agent. We have reported that OK-PSA has an ability to mature dendritic cells (DCs) via Toll-like receptor (TLR) 4 signaling. DCs are potent antigen-presenting cells which promote immune responses against tumor cells. It is important to mature DCs capturing tumor antigen to enhance their anti-tumor activity. TLR4 plays a significant role in recognition of bacterial components as well as in activation of innate and acquired immunity. In the current study, we investigated the role of TLR4 in the anti-tumor effect of intratumoral administration of bone marrow-derived DCs followed by OK-PSA against established tumors in mice. C57BL/6 mice which are expressing wild-type TLR4, and C57BL/6-derived TLR4-knockout (TLR4-/-) mice were used for the present experiments. We first examined the effect of OK-PSA in the in vitro maturation of DCs. OK-PSA increased the expression ...
A properly functioning adaptive immune system signifies the best features of life. It is diverse beyond compare, tolerant without fail, and capable of behaving appropriately with a myriad of infections and other challenges. Dendritic cells are required to explain how this remarkable system is energized and directed. I frame this article in terms of the major decisions that my colleagues and I have made in dendritic cell science and some of the guiding themes at the time the decisions were made. As a result of progress worldwide, there is now evidence of a central role for dendritic cells in initiating antigen-specific immunity and tolerance. The in vivo distribution and development of a previously unrecognized white cell lineage is better understood, as is the importance of dendritic cell maturation to link innate and adaptive immunity in response to many stimuli. Our current focus is on antigen uptake receptors on dendritic cells. These receptors enable experiments involving selective targeting of
Inflammatory bowel disease (IBD) is a chronic inflammatory condition caused by an aberrant immune response to microbial components of the gastrointestinal tract. Plasmacytoid dendritic cells (pDCs) are innate immune cells specialized in the production of type I interferons and were recently implicated in the pathogenesis of autoimmune disorders such as lupus and scleroderma. While pDCs were shown to infiltrate intestinal mucosa of IBD patients and proposed to participate in intestinal inflammation, their net contribution to the disease remains unclear. We addressed this question by targeting the pDC-specific transcription factor TCF4 (E2-2) in experimental IBD caused by deficiency of Wiskott-Aldrich syndrome protein (WASP) or of interleukin-10 (IL-10). Monoallelic Tcf4 deletion, which was previously shown to abrogate experimental lupus, did not affect autoimmunity manifestations or colitis in WASP-deficient animals. Furthermore, conditional biallelic Tcf4 targeting resulted in a near-complete pDC
Dendritic cells are the messengers of the immune system, transporting antigens from sites of inflammation to the lymph organs that serve as central hubs for immune activation. Ufer et al. have identified a neuronal plasticity molecule-activity-regulated cytoskeleton-associated protein/activity-regulated gene 3.1 (Arc/Arg3.1)-that is expressed in migratory dendritic cells in the skin. Arc/Arg3.1 regulates cytoskeletal changes in dendritic cells, accelerating migration in response to inflammation. Moreover, Arc/Arg3.1 was required for inducing T cell responses in two different disease models-experimental autoimmune encephalitis and allergic contact dermatitis. Targeting Arc/Arg3.1 may therefore be a therapeutic strategy to modify dendritic cell immunotherapy. ...
According to Daniel Hawiger, dendritic cells are the music directors, telling other lymphocytes such as T cells what to do and how to do it. Hawiger is the senior author of a study recently published in the journal Immunity. The study (Immunomodulatory Functions of BTLA and HVEM Govern Induction of Extrathymic Regulatory T Cells and Tolerance by Dendritic Cells) helps to understand how dendritic cells direct T lymphocytes to learn tolerance for the bodys own antigens. T cells are the immune systems fighters, Hawiger said. Dendritic cells help train T cells to distinguish between self and non-self.. Dendritic cells were first described by Ralph Steinman in the 1970s and, since the 1980s, it has been known that one of the major functions of dendritic cells is antigen presentation-the display of peptides derived from viral and cancer antigens to T lymphocytes. Following recognition of peptides, T lymphocytes become activated and initiate a complex set of events. These events require the ...
TY - JOUR. T1 - Decellularized lymph node scaffolding as a carrier for dendritic cells to induce anti-tumor immunity. AU - Lin, Hung Jun. AU - Wang, Weu. AU - Huang, Yi You. AU - Liao, Wei Tsen. AU - Lin, Ting Yu. AU - Lin, Shyr Yi. AU - Liu, Der Zen. PY - 2019/11. Y1 - 2019/11. N2 - In recent decades, the decellularized extracellular matrix (ECM) has shown potential as a promising scaffold for tissue regeneration. In this study, an organic acid decellularized lymph node (dLN) was developed as a carrier for dendritic cells (DCs) to induce antitumor immunity. The dLNs were prepared by formic acid, acetic acid, or citric acid treatment. The results showed highly efficient removal of cell debris from the lymph node and great preservation of ECM architecture and biomolecules. In addition, bone marrow dendritic cells (BMDCs) grown preferably inside the dLN displayed the maturation markers CD80, CD86, and major histocompatibility complex (MHC)-II, and they produced high levels of interleukin (IL)-1β, ...
TY - JOUR. T1 - Stromal fibroblasts support dendritic cells to maintain IL-23/Th17 responses after exposure to ionizing radiation. AU - Malecka, Anna. AU - Wang, Qunwei. AU - Shah, Sabaria. AU - Sutavani, Ruhcha V.. AU - Spendlove, Ian. AU - Ramage, Judith M.. AU - Greensmith, Julie. AU - Franks, Hester A.. AU - Gough, Michael J.. AU - Saalbach, Anja. AU - Patel, Poulam M.. AU - Jackson, Andrew M.. PY - 2016/8/1. Y1 - 2016/8/1. N2 - Dendritic cell function is modulated by stromal cells, including fibroblasts. Although poorly understood, the signals delivered through this crosstalk substantially alter dendritic cell biology. This is well illustrated with release of TNF-α/IL-1β from activated dendritic cells, promoting PGE2 secretion from stromal fibroblasts. This instructs dendritic cells to up-regulate IL-23, a key Th17-polarizing cytokine. We previously showed that ionizing radiation inhibited IL-23 production by human dendritic cells in vitro. In the present study, we investigated the ...
Supplementary Material for: Cross-Talk between Human Dendritic Cell Subsets Influences Expression of RNA Sensors and Inhibits Picornavirus Infection
Insufficient elimination of the hepatitis C virus (HCV) during acute infection results in chronic disease in the majority of patients due to weak virus-specific immune responses. Dendritic cells (DC) play a central role in recognition of HCV and in induction of innate and adaptive immune responses. In this study, we evaluated the frequency and functions of plasmacytoid dendritic cells (PDC) and myeloid dendritic cells (MDC) in patients with chronic HCV infection. We found that both the numbers and IFNalpha production capacity of blood PDC were significantly reduced in patients with chronic HCV infection compared to normal controls. While the frequency of MDC was not affected in chronic HCV, the allostimulatory capacity of monocyte-derived MDC was significantly decreased compared to normals. Lipopolysaccharide (LPS)-induced maturation improved the allostimulatory capacity of HCV infected patients MDC that still remained significantly lower compared to normal controls. Our experiments revealed that MDC
Alpha-fetoprotein (AFP) is a tumor-associated glycoprotein that functions in regulation of both ontogenic and oncogenic growth. Recent study showed that AFP can induce apoptosis or impair monocyte-derived dendritic cell (MDDC) function. However, it is still unclear which AFP domain (D-AFP) plays major role in this function. As expected monocytes cultured in the presence of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Interleukin-4 (IL-4) developed into MDDC. Up-regulation of HLA-DR and CD11c as well as loss of CD14 molecules could be observed. Full length AFP (FL-AFP), domain 2 AFP (D2-AFP) and D3-AFP, but not D1-AFP, significantly inhibited the expression of HLA-DRhigh/CD11chigh and CD80+/CD86high molecules. In contrast, CD83 expression was substantially down-regulated in all samples. Expression of CD40 was significantly suppressed by FL-AFP but not by any D-AFPs. Finally, both FL-AFP and D-AFP impaired the MDDC ability to secrete IL-12 (p70). D2- and D3- but not D1-AFP extensively
Alpha-fetoprotein (AFP) is a tumor-associated glycoprotein that functions in regulation of both ontogenic and oncogenic growth. Recent study showed that AFP can induce apoptosis or impair monocyte-derived dendritic cell (MDDC) function. However, it is still unclear which AFP domain (D-AFP) plays major role in this function. As expected monocytes cultured in the presence of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF) and Interleukin-4 (IL-4) developed into MDDC. Up-regulation of HLA-DR and CD11c as well as loss of CD14 molecules could be observed. Full length AFP (FL-AFP), domain 2 AFP (D2-AFP) and D3-AFP, but not D1-AFP, significantly inhibited the expression of HLA-DRhigh/CD11chigh and CD80+/CD86high molecules. In contrast, CD83 expression was substantially down-regulated in all samples. Expression of CD40 was significantly suppressed by FL-AFP but not by any D-AFPs. Finally, both FL-AFP and D-AFP impaired the MDDC ability to secrete IL-12 (p70). D2- and D3- but not D1-AFP extensively
Dendritic cells (DCs) play important roles in immune recognition of invading pathogens during infections. They bridge the two branches of innate and adaptive immunity and are thought to be unique in their capacity to prime naive T cell responses. DCs act as sentinels, responding to evolutionary-conserved microbial structures as indicators of infection, using pattern recognition receptors. TLRs are the best characterized group of pattern recognition receptors that recognize pathogen-associated molecular patterns such as LPS, peptidoglycans, flagellin, lipoteichoic acid, or unmethylated CpG DNA, and they can stimulate activation of the innate immune system (1, 2). As a result, DCs change their activation state, gaining immunostimulatory capacity hallmarked by reinforced migratory homing to secondary lymphoid tissues, increased Ag processing and presentation, expression of costimulatory molecules, and secretion of proinflammatory cytokines. These activation-associated changes enable DCs to prime ...
While much is understood about dendritic cells and their role in the immune system, the study of these cells is critical to gain a more complete understanding of their function. Dendritic cell isolation from mouse body tissues can be difficult and the number of cells isolated small. This protocol describes the growth of large number of dendritic cells from the culture of mouse
TY - JOUR. T1 - A subset of toll-like receptor ligands induces cross-presentation by bone marrow-derived dendritic cells. AU - Datta, Sandip K.. AU - Redecke, Vanessa. AU - Prilliman, Kiley R.. AU - Takabayashi, Kenji. AU - Corr, Maripat. AU - Tallant, Thomas. AU - DiDonato, Joseph. AU - Dziarski, Roman. AU - Akira, Shizuo. AU - Schoenberger, Stephen P.. AU - Raz, Eyal. PY - 2003/4/15. Y1 - 2003/4/15. N2 - Dendritic cells (DCs) are capable of cross-presenting exogenous Ag to CD8+ CTLs. Detection of microbial products by Toll-like receptors (TLRs) leads to activation of DCs and subsequent orchestration of an adaptive immune response. We hypothesized that microbial TLR ligands could activate DCs to cross-present Ag to CTLs. Using DCs and CTLs in an in vitro cross- presentation system, we show that a subset of microbial TLR ligands, namely ligands of TLR3 (poly(inosinic-cytidylic) acid) and TLR9 (immunostimulatory CpG DNA), induces cross-presentation. In contrast to presentation of Ag to CD4+ T ...
The Plasmacytoid Dendritic Cell Isolation Kit II allows the isolation of untouched human plasmacytoid dendritic cells (PDCs) from PBMCs. Having evolved from the first-generation kit (# 130-092-207), it now offers even better cell purity and yield in a faster procedure. - Belgique
Aitouche, A and Rugeles, MT and Zeevi, A and Fung, JJ and Starzl, TE and Rao, AS (1997) Documentation in bone-marrow-augmented organ recipients of the presence of dendritic cell progenitors of donor origin. Transplantation Proceedings, 29 (4). 2175 - 2176. ISSN 0041-1345 ...
TY - JOUR. T1 - Generation of mucosal dendritic cells from bone marrow reveals a critical role of retinoic acid. AU - Feng, Ting. AU - Cong, Yingzi. AU - Qin, Hongwei. AU - Benveniste, Etty N.. AU - Elson, Charles O.. PY - 2010/11/15. Y1 - 2010/11/15. N2 - It is unknown how dendritic cells (DCs) become specialized as mucosal DCs and maintain intestinal homeostasis. We report that a subset of bone marrow cells freshly isolated from C57BL/6 mice express the retinoic acid (RA)-synthesizing enzyme aldehyde dehydrogenase family 1, subfamily A2 (ALDH1a2) and are capable of providing RA to DC precursors in the bone marrow microenvironment. RA induced bone marrow-derived DCs to express CCR9 and ALDH1a2 and conferred upon them mucosal DC functions, including induction of Foxp3 + regulatory T cells, IgA-secreting B cells, and gut-homing molecules. This response of DCs to RA was dependent on a narrow time window and stringent dose effect. RA promoted bone marrow-derived DC production of bioactive TGF-β by ...
TY - JOUR. T1 - Differential modulation of TLR-3 and TLR-4 mediated dendritic cell maturation and function by progesterone. AU - Jones, Leigh A.. AU - Kreem, Shrook. AU - Shweash, Muhannad. AU - Paul, Andrew. AU - Alexander, James. AU - Roberts, Craig W.. PY - 2010/10/15. Y1 - 2010/10/15. N2 - The role of progesterone in modulating dendritic cell (DC) function following stimulation of different TLRs is relatively unknown. We compared the ability of progesterone to modulate murine bone marrow-derived DC cytokine production (IL-6 and IL-12) and costimulatory molecule expression (CD40, CD80, and CD86) induced by either TLR3 or TLR4 ligation and determined whether activity was via the progesterone receptor (PR) or glucocorticoid receptor (GR) by comparative studies with the PR-specific agonist norgestrel and the GR agonist dexamethasone. Progesterone was found to downregulate, albeit with different sensitivities, both TLR3- and TLR4-induced IL-6 production entirely via the GR, but IL-12p40 ...
Biodegradable nanoparticles have been employed for vaccine delivery, frequently admixed with adjuvants. Surprisingly, there is little information on their modulation of immune responses, speculated to be negligible. We analyzed the immunomodulatory capacity of alginate-coated chitosan nanogels (Ng), on porcine and human blood dendritic cells (DCs), when applied with defined adjuvants targeting different DC subpopulations. DC maturation, cytokine production and cell migration were assessed. Ng differentially influenced the immunomodulatory characteristics of individual Toll-like receptor (TLR) ligands: Pam3Cys-SK4-induced IL-1β was enhanced; CpG-oligodeoxynucleotides (CpG-ODN)-induced IFN-α, IL-6 and TNFα were impaired; CpG-ODN-induced CD86 and CCR7, and cell migration, were diminished-plasmacytoid DCs (pDCs) were particularly sensitive. Therein, the Ng influence on DC endocytosis of the TLR ligands was apparently a major contributory element. This demonstrates the importance of predefi
Ectopic expression of transcription factors has been used to reprogram differentiated somatic cells toward pluripotency or to directly reprogram them to other somatic cell lineages. This concept has been explored in the context of regenerative medicine. Here, we set out to generate dendritic cells (DCs) capable of presenting antigens from mouse and human fibroblasts. By screening combinations of 18 transcription factors that are expressed in DCs, we have identified PU.1, IRF8, and BATF3 transcription factors as being sufficient to reprogram both mouse and human fibroblasts to induced DCs (iDCs). iDCs acquire a conventional DC type 1-like transcriptional program, with features of interferon-induced maturation. iDCs secrete inflammatory cytokines and have the ability to engulf, process, and present antigens to T cells. Furthermore, we demonstrate that murine iDCs generated here were able to cross-present antigens to CD8+ T cells. Our reprogramming system should facilitate better understanding of ...
Plasmacytoid DCs (pDCs) comprise one of two major subsets of human DCs. The myeloid subset is characterized by the presence of CD11c, whereas pDCs correspond to a small subset of CD11c-negative circulating blood DCs (1). Human pDCs are CD4+ CD45RA+IL-3Rα+ (CD123) ILT3+ILT1− CD11c− lineage− cells (2). Two additional markers, BDCA-2 and BDCA-4 are expressed on human pDCs in peripheral blood and bone marrow (3).. In response to viral and bacterial stimuli, pDCs can mature and produce large amounts of type I IFNs (IFN-α/β) (4). Type I interferons activate NK cell cytolytic activity, but protect uninfected cells from NK cell-mediated lysis and affect T cell function by inducing Th1 differentiation (5). Moreover, type I interferons promote differentiation, maturation, and immunostimulatory functions of DCs.. Recent findings suggest that pDCs play an important role in the balance of immune responses. Although resting pDCs may induce regulatory responses, their activated counterparts have a ...
Mimicking the immunoregulatory properties of primary dendritic cells in vitro − A rational approach to design a test system ...
The Blood Dendritic Cell Enumeration Kit was developed for easy identification and enumeration of dendritic cells (DCs) and DC subsets in whole blood or PBMCs by flow cytometry. All reagents required for the analysis are included in the kit. Applications of the kit include monitoring of peripheral blood DC frequency and number, for example, after hematopoietic stem cell mobilization3 , or in the course of pathogenic infections, for example by HIV.4 Furthermore, DC numbers were determined in patients with chronic graft versus host disease5 , inflammatory bowel disease6 , psoriatic arthritis and rheumatoid arthritis10 , under long-term immunosuppression8 , lymphoproliferative disease of granular lymphocytes9 , or in patients with hepatocellular carcinoma, in order to analyze the immunosuppressive role of IL-10 on circulating dendritic cells7 . - Latvija
TY - JOUR. T1 - In vivo and in vitro analyses of α-galactosylceramide uptake by conventional dendritic cell subsets using its fluorescence-labeled derivative. AU - Ushida, Maki. AU - Iyoda, Tomonori. AU - Kanamori, Mitsuhiro. AU - Watarai, Hiroshi. AU - Takahara, Kazuhiko. AU - Inaba, Kayo. PY - 2015/12/1. Y1 - 2015/12/1. N2 - Conventional dendritic cells (cDCs) present α-galactosylceramide (αGC) to invariant natural killer T (iNKT) cells through CD1d. Among cDC subsets, CD8+ DCs efficiently induce IFN-γ production in iNKT cells. Using fluorescence-labeled αGC, we showed that CD8+ DCs incorporated larger amounts of αGC and kept it intact longer than CD8- DCs. Histological analyses revealed that Langerin+CD8+ DCs in the splenic marginal zone, which was the unique equipment to capture blood-borne antigens, preferably incorporated αGC, and the depletion of Langerin+ cells decreased IFN-γ and IL-12 production in response to αGC. Furthermore, splenic Langerin+CD8+ DCs expressed more ...
T cell stimulatory capacity of DCs cultured with PGE2. Day-5 DCs were recultured in the absence or presence of PGE2 (10 μM), TNF-α (1,000 U/ml), or PGE2 pl

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Dendritic Cell News and Research. RSS Dendritic Cells are a special type of immune cell that is found in tissues, such as the ... A dendritic cell is a type of phagocyte and a type of antigen-presenting cell (APC). Further Reading. *What are Dendritic Cells ... Known as CD11c+ dendritic cells, these new cells are more susceptible to HIV infection and can then transmit the virus to other ... at Lund University in Sweden has successfully reprogrammed mouse and human skin cells into immune cells called dendritic cells. ...
Dendritic epidermal T-cell activation.. Sharp LL1, Jameson JM, Witherden DA, Komori HK, Havran WL. ... Dendritic epidermal T cells (DETC) are the skin-resident gammadeltaIEL and serve as a model system for gammadeltaIEL in other ... Although gammadelta T cells compose a small proportion of lymphocytes in lymphoid compartments and peripheral blood, they are ... the major T-cell population present in epithelial tissues. However, the role played by gammadelta TCR expressing ...
2010) TGF-beta1 accelerates dendritic cell differentiation from common dendritic cell progenitors and directs subset ... 2008) Transcription factor E2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell 135(1): ... 2010) Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. ... Dendritic cell fate is determined by BCL11A. Gregory C. Ippolito, Joseph D. Dekker, Yui-Hsi Wang, Bum-Kyu Lee, Arthur L. ...
These proceedings contain selected contributions from the participants to the Fourth International Symposium on Dendritic cells ... Dendritic Cell Development and Migration. * Dendritic Cell Development and Maturation Ralph M. Steinman, Maggie Pack, Kayo ... Studies on dendritic cells (DC) have been greatly hampered by the difficulties in preparing sufficient cell numbers and in a ... T Cell-Mediated Terminal Maturation of Dendritic cells Paul R. Bergstresser, Toshiyuki Kitajima, Shan Xu, Kiyoshi Ariizumi, ...
This work examines the dendritic cell algorithm (DCA) from a mathematical perspective. By representing the signal pro-cessing ... using artificially generated data and a novel visualisation tech-nique that allows an entire population of dendritic cells to ... dendritic cell algorithm geometrical insight serious drawback linear classifier novel visualisation tech-nique signal pro- ... This work examines the dendritic cell algorithm (DCA) from a mathematical perspective. By representing the signal pro-cessing ...
Dendritic cells capture antigens with their threadlike tentacles and present the antigens to T lymphocytes (T cells), ... A type of antigen-presenting cell found in many tissues throughout the body. ... Dendritic Cell Dendritic Cell Speaker A type of antigen-presenting cell found in many tissues throughout the body. Dendritic ... cells capture antigens with their threadlike tentacles and present the antigens to T lymphocytes (T cells), stimulating an ...
... we have used two approaches to search at the genetic level for molecules which are specifically expressed by these cells. First ... To increase our understanding of dendritic cell (DC) function ... Dendritic Cell cDNA Library Mannose Receptor Dendritic Cell ... 1997) Analysis of Dendritic Cells at the Genetic Level. In: Ricciardi-Castagnoli P. (eds) Dendritic Cells in Fundamental and ... Dendritic cells freshly isolated from human blood express CD4 and mature into typical immunostimulatory dendritic cells after ...
In the present work two opposing situations known to affect dendritic cells are analyzed: tumor growth, leading to a ... The modifications suffered by these cells have consequences in the way the organism may respond. ... Dendritic cells are antigen-presenting cells capable of either activating the immune response or inducing and maintaining ... 3. Dendritic Cell Plasticity and Subtypes. Dendritic cells are heterogeneous and dynamic cells. Dendritic cells were first ...
Neurons compute by integrating synaptic inputs across their dendritic arbor. Here, the authors show that distinct cell-types of ... However, it is far from understood how different cell types tune this process to establish cell-type specific computations. ... exhibit type-specific dendritic integration profiles: in contrast to the other types, dendrites of transient Off alpha cells ... We show that differences between cell types can likely be explained by differences in backpropagation efficiency, arising from ...
... for blastic plasmacytoid dendritic cell neoplasm (BPDCN) in adults and in pediatric patients 2 years and older. ...
Purchase Immunobiology of Dendritic Cells Part A, Volume 348 - 1st Edition. Print Book & E-Book. ISBN 9780128183519, ... The Interaction of Dendritic Cells With Cancer Cells, The Role of Dendritic Cells in Human Diseases, and Dendritic Cells-based ... 4. Interaction of dendritic cells with cancer cells. Karolina Palucka. 5. Role of dendritic cells in human diseases. Kristen ... 1. Origin and development of dendritic cells. Julie Helft. 2. Dendritic cell subsets and locations. Sreekumar Balan. 3. Antigen ...
1998) Monocyte-derived dendritic cells have a phenotype comparable to that of dermal dendritic cells and display ... Over 7 ± 2.5% (n = 6) of Alexa 488+ cells displayed dendritic filaments emanating from the cell body. These dendrites varied in ... 2000) Lectin ligands on human dendritic cells and identification of a peanut agglutinin positive subset in blood. Cell Immunol ... 2006) The efficient isolation of murine splenic dendritic cells and their cytochemical features. Histochem Cell Biol 126:275- ...
Dex have the potential to facilitate immune cell-dependent tumor rejection and have distinct advantages over cell-based ... DC-derived exosomes (Dex) are nanometer-sized membrane vesicles that are secreted by the sentinel antigen-presenting cells of ... This Review will evaluate the interactions of Dex with immune cells, their clinical progress, and the future of Dex ... as well as the propensity of these nanovesicles to mediate T and NK cell-based immune responses in patients. ...
Dendritic-cell exosomes cross-present Toll-like receptor-ligands and activate bystander dendritic cells. Cell Immunol. 2014;289 ... I. Dendritic cell-derived exosomes transfer functional MHC class I/peptide complexes to dendritic cells. J Immunol. 2004;172(4 ... Dendritic cell exosomes directly kill tumor cells and activate natural killer cells via TNF superfamily ligands. Oncoimmunology ... Short-range exosomal transfer of viral RNA from infected cells to plasmacytoid dendritic cells triggers innate immunity. Cell ...
Some interfaces of dendritic cell biology. APMIS 2003;111:675-97. The field of dendritic cell (DC) biology is robust, with ... regulatory T cells, peripheral T cell deletion), not just the initial priming or induction of T cell-mediated immunity, which ... DCs are now known to influence many different classes of lymphocytes (B, NK, NKT) and many types of T cell responses (Th1/Th2, ... A third interface is with cell biology. This is a critical discipline to understand at the subcellular and molecular levels the ...
Dendritic cells are highly adapted to their role of presenting antigen and directing immune responses. Developmental studies ... dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong TH17/TH1 T-cell responsesJ Allergy Clin ... "Dermal Dendritic Cells" comprise two distinct populations: CD1+ dendritic cells and CD209+ macrophagesJ Invest DermatolYear: ... Nectin-like protein 2 defines a subset of T-cell zone dendritic cells and is a ligand for class-I-restricted T-cell-associated ...
Dendritic cell populations in the skin of human and mice. aCommon cellular markers associated with human and mice skin DC ... Harnessing dendritic cells in inflammatory skin diseases.. Chu CC1, Di Meglio P, Nestle FO. ... The skin immune system harbors a complex network of dendritic cells (DCs). Recent studies highlight a diverse functional ... In the steady state, CD207+ DDCs (found in the dermis of mice) can capture dead cells or tissue antigens and promote T cell ...
... Jonathan S. Tam and Mitchell H. Grayson ... Dendritic cells are important residents of the lung environment. They have been associated with asthma and other inflammatory ... Recent studies have begun to show the critical importance of the dendritic cell in this process. This paper focuses on these ... In addition to their antigen-presenting functions, dendritic cells have the ability to modulate the lung environment to promote ...
... cell leukemia/lymphoma, is very often misdiagnosed and under-reported. ... Blastic plasmacytoid dendritic cell neoplasm (BPDCN), previously known as natural killer (NK) ... Blastic plasmacytoid dendritic cell neoplasm (BPDCN), previously known as natural killer (NK) cell leukemia/lymphoma, is ... Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is very often misdiagnosed and under-reported. Diagnosing a patient with ...
Dendritic cells have also been found in turtles. A dendritic cell Play media A well-resolved dendritic cell drags a conidium ... three classical dendritic cell subsets and one plasmacytoid dendritic cell subset. At least some of these dendritic cell ... concurrent interaction of all three cell types, namely CD4+ T helper cells, CD8+ T cells and dendritic cells, seems to be ... The morphology of dendritic cells results in a very large surface-to-volume ratio. That is, the dendritic cell has a very large ...
... is their coordinated expression at the interface between antigen-specific T cells and antigen-presenting dendritic cells and, ... are the master regulators of T cell responses to foreign antigens. This Review discusses how the tumour necrosis factor (TNF) ... and their expression by cells of the immune system makes them appealing targets for immunomodulation. One common theme for TNF ... superfamily of molecules influences DC biology and the outcome for T cell immune responses. Members of the tumour necrosis ...
Oncologist Sumana Prem Kumar discusses Dendritic Cell Therapy, the Personalized Cancer Immunotherapy to treat cancer, which is ... Dendritic Cell Vaccine. Dendritic Cell Vaccine or Dendritic Cell Therapy (DCT) is an antigen extracted from the cancerous tumor ... About Dendritic Cell therapy Dendritic cells are found in the blood stream and are a unique set of antigen-producing cells that ... The neutrophils cells were then directed to the dormant dendritic cells. The dormant cells now activated, attacked the cancer ...
Dendritic and Antigen Presenting Cell RT2 Profiler PCR Array The Human Dendritic and Antigen Presenting Cell RT² Profiler PCR ... Dendritic and Antigen Presenting Cell RT2 Profiler PCR Array The Mouse Dendritic and Antigen Presenting Cell RT² Profiler PCR ... Dendritic and Antigen Presenting Cell RT2 Profiler PCR Array The Rat Dendritic and Antigen Presenting Cell RT² Profiler PCR ... However, the known roles of dendritic cell dysregulation in allergy and autoimmune diseases make these cells an important ...
T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an ... T cell responses. In vivo, cross-presentation is mainly carried out by specific dendritic cell (DC) subsets through an ... Cross-presentation by dendritic cells Nat Rev Immunol. 2012 Jul 13;12(8):557-69. doi: 10.1038/nri3254. ...
Dendritic Spikes and Their Inhibition in Alligator Purkinje Cells. By Rodolfo Llinás, Charles Nicholson, John A. Freeman, Dean ... Dendritic Spikes and Their Inhibition in Alligator Purkinje Cells. By Rodolfo Llinás, Charles Nicholson, John A. Freeman, Dean ... Dendritic Spikes and Their Inhibition in Alligator Purkinje Cells Message Subject. (Your Name) has forwarded a page to you from ... Alligator Purkinje cells generate action potentials in the peripheral dendritic tree, after synaptic depolarization via ...
Since DCs possess the intrinsic capacity to polarize CD4+ helper cells, it is critical to understand the immunological roles of ... are antigen presenting cells that are characterized by a potent capacity to initiate immune responses. DCs comprise several ... DCs become mature and subsequently present antigens to CD4+ T cells. ... Dendritic cells (DCs) are antigen presenting cells that are characterized by a potent capacity to initiate immune responses. ...
Find clinical trials studying therapeutic autologous dendritic cells. ... Vaccines made from a persons tumor cells and special blood cells (dendritic cells) may help the body build an effective immune ... Dendritic Cell Therapy after Cryosurgery in Combination with Pembrolizumab in Treating Patients with Stage III-IV Melanoma That ... Giving dendritic cell therapy after cryosurgery in combination with pembrolizumab may work better in treating patients with ...
Follicular dendritic cells (FDCs) are cells of the immune system found in primary and secondary lymph follicles of the B cell ... and the skin of patients with pseudo B cells lymphoma. Follicular dendritic cells participate in HIV-1 infection development ... "Endocytosis and recycling of immune complexes by follicular dendritic cells enhances B cell binding and activation". Frontiers ... and differentiation into high-affinity plasma cells and memory B cells. Adhesion between FDCs and B cells is mediated by ICAM-1 ...
... are professional antigen-presenting cells, located throughout the body. They form the first line of defence against pathogens. ... Dendritic cells (DCs) are professional antigen-presenting cells, located throughout the body. They form the first line of ... Developing a new drug that targets plasmacytoid dendritic cells for the treatment of lupus ... A new regulator of stemness to create dendritic cell factories for immunotherapy ...
... Chen M., Huang L., Shabier Z., Wang J. ... The lifespan of dendritic cells (DCs) can potentially influence immune responses by affecting the duration of DCs in ... or T cells. Transfection with Bcl-2 or Bcl-xL prolonged the survival of mouse primary mDCs in vitro, while deletion of Bcl-2 ...

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