Dictionaries, MedicalDictionaries as Topic: Lists of words, usually in alphabetical order, giving information about form, pronunciation, etymology, grammar, and meaning.T-Lymphocytes: 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.CD4-Positive T-Lymphocytes: 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.CD8-Positive T-Lymphocytes: 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.Dictionaries, ChemicalAntigens, CD3: Complex of at least five membrane-bound polypeptides in mature T-lymphocytes that are non-covalently associated with one another and with the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL). The CD3 complex includes the gamma, delta, epsilon, zeta, and eta chains (subunits). When antigen binds to the T-cell receptor, the CD3 complex transduces the activating signals to the cytoplasm of the T-cell. The CD3 gamma and delta chains (subunits) are separate from and not related to the gamma/delta chains of the T-cell receptor (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA).Terminology as Topic: The terms, expressions, designations, or symbols used in a particular science, discipline, or specialized subject area.Antigens, CD8: 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.Photosensitivity Disorders: Abnormal responses to sunlight or artificial light due to extreme reactivity of light-absorbing molecules in tissues. It refers almost exclusively to skin photosensitivity, including sunburn, reactions due to repeated prolonged exposure in the absence of photosensitizing factors, and reactions requiring photosensitizing factors such as photosensitizing agents and certain diseases. With restricted reference to skin tissue, it does not include photosensitivity of the eye to light, as in photophobia or photosensitive epilepsy.Crowdsourcing: Social media model for enabling public involvement and recruitment in participation. Use of social media to collect feedback and recruit volunteer subjects.Vocabulary, Controlled: A specified list of terms with a fixed and unalterable meaning, and from which a selection is made when CATALOGING; ABSTRACTING AND INDEXING; or searching BOOKS; JOURNALS AS TOPIC; and other documents. The control is intended to avoid the scattering of related subjects under different headings (SUBJECT HEADINGS). The list may be altered or extended only by the publisher or issuing agency. (From Harrod's Librarians' Glossary, 7th ed, p163)Unified Medical Language System: A research and development program initiated by the NATIONAL LIBRARY OF MEDICINE to build knowledge sources for the purpose of aiding the development of systems that help health professionals retrieve and integrate biomedical information. The knowledge sources can be used to link disparate information systems to overcome retrieval problems caused by differences in terminology and the scattering of relevant information across many databases. The three knowledge sources are the Metathesaurus, the Semantic Network, and the Specialist Lexicon.Immune Evasion: Methods used by pathogenic organisms to evade a host's immune system.Hemorrhagic Fevers, Viral: A group of viral diseases of diverse etiology but having many similar clinical characteristics; increased capillary permeability, leukopenia, and thrombocytopenia are common to all. Hemorrhagic fevers are characterized by sudden onset, fever, headache, generalized myalgia, backache, conjunctivitis, and severe prostration, followed by various hemorrhagic symptoms. Hemorrhagic fever with kidney involvement is HEMORRHAGIC FEVER WITH RENAL SYNDROME.Hantavirus: A genus of the family BUNYAVIRIDAE causing HANTAVIRUS INFECTIONS, first identified during the Korean war. Infection is found primarily in rodents and humans. Transmission does not appear to involve arthropods. HANTAAN VIRUS is the type species.Histocompatibility Antigens Class I: 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.Immunity, Innate: 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.Hantavirus Infections: Infections with viruses of the genus HANTAVIRUS. This is associated with at least four clinical syndromes: HEMORRHAGIC FEVER WITH RENAL SYNDROME caused by viruses of the Hantaan group; a milder form of HFRS caused by SEOUL VIRUS; nephropathia epidemica caused by PUUMALA VIRUS; and HANTAVIRUS PULMONARY SYNDROME caused by SIN NOMBRE VIRUS.Viral Proteins: Proteins found in any species of virus.Hemorrhagic Fever with Renal Syndrome: An acute febrile disease occurring predominately in Asia. It is characterized by fever, prostration, vomiting, hemorrhagic phenonema, shock, and renal failure. It is caused by any one of several closely related species of the genus Hantavirus. The most severe form is caused by HANTAAN VIRUS whose natural host is the rodent Apodemus agrarius. Milder forms are caused by SEOUL VIRUS and transmitted by the rodents Rattus rattus and R. norvegicus, and the PUUMALA VIRUS with transmission by Clethrionomys galreolus.Marburg Virus Disease: An RNA virus infection of rhesus, vervet, and squirrel monkeys transmissible to man.Hantaan virus: The type species of the genus HANTAVIRUS infecting the rodent Apodemus agrarius and humans who come in contact with it. It causes syndromes of hemorrhagic fever associated with vascular and especially renal pathology.Dendritic Cells: 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).Lymphocytes, Tumor-Infiltrating: Lymphocytes that show specificity for autologous tumor cells. Ex vivo isolation and culturing of TIL with interleukin-2, followed by reinfusion into the patient, is one form of adoptive immunotherapy of cancer.Mice, Inbred C57BLMice, Inbred BALB CLymphocyte Activation: 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.Cytokines: 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.Logic: The science that investigates the principles governing correct or reliable inference and deals with the canons and criteria of validity in thought and demonstration. This system of reasoning is applicable to any branch of knowledge or study. (Random House Unabridged Dictionary, 2d ed & Sippl, Computer Dictionary, 4th ed)Flow Cytometry: 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.Immunotherapy: 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.Allergy and Immunology: A medical specialty concerned with the hypersensitivity of the individual to foreign substances and protection from the resultant infection or disorder.NK Cell Lectin-Like Receptor Subfamily C: A subclass of NK cell lectin-like receptors that associates with members of NK CELL LECTIN-LIKE RECEPTOR SUBFAMILY D to form heterodimeric receptors for HLA-E antigen.Receptors, Immunologic: 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.NK Cell Lectin-Like Receptor Subfamily D: A subclass of NK cell lectin-like receptors that associates with a variety of members of NK CELL LECTIN-LIKE RECEPTOR SUBFAMILY C to form heterodimeric receptors for HLA-E antigen.Killer Cells, Natural: 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.Adaptive Immunity: 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).Receptors, Natural Killer Cell: Receptors that are specifically found on the surface of NATURAL KILLER CELLS. They play an important role in regulating the cellular component of INNATE IMMUNITY.NK Cell Lectin-Like Receptor Subfamily K: An activating NK cell lectin-like receptor subfamily that regulates immune responses to INFECTION and NEOPLASMS. Members of this subfamily generally occur as homodimers.Receptors, KIR2DL3: A KIR receptor that has specificity for HLA-C ANTIGEN. It is an inhibitory receptor that contains D1 and D2 extracellular immunoglobulin-like domains and a long cytoplasmic tail. It is similar in structure and function to the KIR2DL2 RECEPTORS and the KIR2DL3 RECEPTORS.Graft vs Host Disease: The clinical entity characterized by anorexia, diarrhea, loss of hair, leukopenia, thrombocytopenia, growth retardation, and eventual death brought about by the GRAFT VS HOST REACTION.Aralia: A plant genus in the family ARALIACEAE, order Apiales, subclass Rosidae. It includes Aralia californica S. Watson, Aralia nudicaulis L., and Aralia racemosa L.Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS.Autopsy: Postmortem examination of the body.Mice, SCID: Mice homozygous for the mutant autosomal recessive gene "scid" which is located on the centromeric end of chromosome 16. These mice lack mature, functional lymphocytes and are thus highly susceptible to lethal opportunistic infections if not chronically treated with antibiotics. The lack of B- and T-cell immunity resembles severe combined immunodeficiency (SCID) syndrome in human infants. SCID mice are useful as animal models since they are receptive to implantation of a human immune system producing SCID-human (SCID-hu) hematochimeric mice.Mice, Inbred NOD: 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.Transplantation, Homologous: Transplantation between individuals of the same species. Usually refers to genetically disparate individuals in contradistinction to isogeneic transplantation for genetically identical individuals.Interleukin Receptor Common gamma Subunit: An interleukin receptor subunit that was originally discovered as a component of the INTERLEUKIN 2 RECEPTOR. It was subsequently found to be a component of several other receptors including the INTERLEUKIN 4 RECEPTOR, the INTERLEUKIN 7 RECEPTOR, the INTERLEUKIN-9 RECEPTOR, the INTERLEUKIN-15 RECEPTOR, and the INTERLEUKIN-21 RECEPTOR. Mutations in the gene for the interleukin receptor common gamma chain have been associated with X-LINKED COMBINED IMMUNODEFICIENCY DISEASES.Bone Marrow Transplantation: The transference of BONE MARROW from one human or animal to another for a variety of purposes including HEMATOPOIETIC STEM CELL TRANSPLANTATION or MESENCHYMAL STEM CELL TRANSPLANTATION.Lymphocytic choriomeningitis virus: The type species of ARENAVIRUS, part of the Old World Arenaviruses (ARENAVIRUSES, OLD WORLD), producing a silent infection in house and laboratory mice. In humans, infection with LCMV can be inapparent, or can present with an influenza-like illness, a benign aseptic meningitis, or a severe meningoencephalomyelitis. The virus can also infect monkeys, dogs, field mice, guinea pigs, and hamsters, the latter an epidemiologically important host.Lymphocytic Choriomeningitis: A form of meningitis caused by LYMPHOCYTIC CHORIOMENINGITIS VIRUS. MICE and other rodents serve as the natural hosts, and infection in humans usually occurs through inhalation or ingestion of infectious particles. Clinical manifestations include an influenza-like syndrome followed by stiff neck, alterations of mentation, ATAXIA, and incontinence. Maternal infections may result in fetal malformations and injury, including neonatal HYDROCEPHALUS, aqueductal stenosis, CHORIORETINITIS, and MICROCEPHALY. (From Joynt, Clinical Neurology, 1996, Ch26, pp1-3)Urea: A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids.Carbamoyl-Phosphate Synthase (Ammonia): An enzyme that catalyzes the formation of carbamoyl phosphate from ATP, carbon dioxide, and ammonia. This enzyme is specific for arginine biosynthesis or the urea cycle. Absence or lack of this enzyme may cause CARBAMOYL-PHOSPHATE SYNTHASE I DEFICIENCY DISEASE. EC 6.3.4.16.Urea Cycle Disorders, Inborn: Rare congenital metabolism disorders of the urea cycle. The disorders are due to mutations that result in complete (neonatal onset) or partial (childhood or adult onset) inactivity of an enzyme, involved in the urea cycle. Neonatal onset results in clinical features that include irritability, vomiting, lethargy, seizures, NEONATAL HYPOTONIA; RESPIRATORY ALKALOSIS; HYPERAMMONEMIA; coma, and death. Survivors of the neonatal onset and childhood/adult onset disorders share common risks for ENCEPHALOPATHIES, METABOLIC, INBORN; and RESPIRATORY ALKALOSIS due to HYPERAMMONEMIA.Interferon Type I: 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).Arenaviridae Infections: Virus diseases caused by the ARENAVIRIDAE.Interferons: Proteins secreted by vertebrate cells in response to a wide variety of inducers. They confer resistance against many different viruses, inhibit proliferation of normal and malignant cells, impede multiplication of intracellular parasites, enhance macrophage and granulocyte phagocytosis, augment natural killer cell activity, and show several other immunomodulatory functions.Receptor, Interferon alpha-beta: A ubiquitously expressed heterodimeric receptor that is specific for both INTERFERON-ALPHA and INTERFERON-BETA. It is composed of two subunits referred to as IFNAR1 and IFNAR2. The IFNAR2 subunit is believed to serve as the ligand-binding chain; however both chains are required for signal transduction. The interferon alpha-beta receptor signals through the action of JANUS KINASES such as the TYK2 KINASE.Pathology, Veterinary: The field of veterinary medicine concerned with the causes of and changes produced in the body by disease.Biological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Education, Veterinary: Use for general articles concerning veterinary medical education.Bibliometrics: The use of statistical methods in the analysis of a body of literature to reveal the historical development of subject fields and patterns of authorship, publication, and use. Formerly called statistical bibliography. (from The ALA Glossary of Library and Information Science, 1983)Biography as Topic: A written account of a person's life and the branch of literature concerned with the lives of people. (Harrod's Librarians' Glossary, 7th ed)Biomedical Research: Research that involves the application of the natural sciences, especially biology and physiology, to medicine.Research: Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)Publications: Copies of a work or document distributed to the public by sale, rental, lease, or lending. (From ALA Glossary of Library and Information Science, 1983, p181)Social Sciences: Disciplines concerned with the interrelationships of individuals in a social environment including social organizations and institutions. Includes Sociology and Anthropology.Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals.

Antitumor effect of allogenic fibroblasts engineered to express Fas ligand (FasL). (1/13590)

Fas ligand is a type II transmembrane protein which can induce apoptosis in Fas-expressing cells. Recent reports indicate that expression of FasL in transplanted cells may cause graft rejection and, on the other hand, tumor cells may lose their tumorigenicity when they are engineered to express FasL. These effects could be related to recruitment of neutrophils by FasL with activation of their cytotoxic machinery. In this study we investigated the antitumor effect of allogenic fibroblasts engineered to express FasL. Fibroblasts engineered to express FasL (PA317/FasL) did not exert toxic effects on transformed liver cell line (BNL) or colon cancer cell line (CT26) in vitro, but they could abrogate their tumorigenicity in vivo. Histological examination of the site of implantation of BNL cells mixed with PA317/FasL revealed massive infiltration of polymorphonuclear neutrophils and mononuclear cells. A specific immune protective effect was observed in animals primed with a mixture of BNL or CT26 and PA317/FasL cells. Rechallenge with tumor cells 14 or 100 days after priming resulted in protection of 100 or 50% of animals, respectively. This protective effect was due to CD8+ cells since depletion of CD8+ led to tumor formation. In addition, treatment of pre-established BNL tumors with a subcutaneous injection of BNL and PA317/FasL cell mixture at a distant site caused significant inhibition of tumor growth. These data demonstrate that allogenic cells engineered with FasL are able to abolish tumor growth and induce specific protective immunity when they are mixed with neoplastic cells.  (+info)

Generation of CD8(+) T-cell responses to Mycobacterium bovis and mycobacterial antigen in experimental bovine tuberculosis. (2/13590)

Protective immunity against tuberculosis is considered to be essentially cell mediated, and an important role for CD8(+) T lymphocytes has been suggested by several studies of murine and human infections. The present work, using an experimental model of infection with Mycobacterium bovis in cattle, showed that live M. bovis elicits the activation of CD8(+) T cells in vitro. However, a sonic extract prepared from M. bovis (MBSE) and protein purified derivative (PPDb) also induced a considerable degree of activation of the CD8(+) T cells. Analysis of proliferative responses of peripheral blood mononuclear cells, purified CD8(+) T cells, and CD8(+) T-cell clones to M. bovis and to soluble antigenic preparations (MBSE, PPDb) showed that the responses of all three types of cells were always superior for live mycobacteria but that strong responses were also obtained with complex soluble preparations. Furthermore, while cytotoxic capabilities were not investigated, the CD8(+) T cells were found to produce and release gamma interferon in response to antigen (live and soluble), which indicated one possible protective mechanism for these cells in bovine tuberculosis. Finally, it was demonstrated by metabolic inhibition with brefeldin A and cytochalasin D at the clonal level that an endogenous pathway of antigen processing is required for presentation to bovine CD8(+) cells and that presentation is also dependent on phagocytosis of the antigen.  (+info)

Fas and Fas ligand interaction induces apoptosis in inflammatory myopathies: CD4+ T cells cause muscle cell injury directly in polymyositis. (3/13590)

OBJECTIVE: To investigate the involvement of the Fas/Fas ligand (Fas/FasL) system in the inflammatory myopathies. METHODS: Frozen muscle sections obtained from 7 patients with polymyositis (PM), 4 patients with dermatomyositis (DM), and 3 controls were studied by immunochemistry. Apoptosis was detected by DNA electrophoresis and in situ labeling using the TUNEL method. RESULTS: Fas was detected on muscle fibers and infiltrating mononuclear cells (MNC) in 6 PM patients and 2 DM patients. FasL was expressed mainly on CD4+ T cells and some CD8+ T cells, and on macrophages surrounding Fas-positive muscles in 4 PM patients and 1 DM patient. In 3 of the 5 patients with FasL-positive MNC, the TUNEL method showed that both invaded myonuclei and MNC underwent apoptosis. Chromosomal DNA from the muscle tissue of these patients showed ladder formation. CONCLUSION: Fas/FasL is involved in muscle cell apoptosis in at least 2 of the inflammatory myopathies, PM and DM. Although CD8+-mediated cytotoxicity is thought to be the main mechanism of muscle injury in PM, our data suggest that CD4+ T cells also directly cause muscle cell damage.  (+info)

Protection against lymphocytic choriomeningitis virus infection induced by a reduced peptide bond analogue of the H-2Db-restricted CD8(+) T cell epitope GP33. (4/13590)

Recent investigations have suggested that pseudopeptides containing modified peptide bonds might advantageously replace natural peptides in therapeutic strategies. We have generated eight reduced peptide bond Psi(CH2-NH) analogues corresponding to the H-2Db-restricted CD8(+) T cell epitope (called GP33) of the glycoprotein of the lymphocytic choriomeningitis virus. One of these pseudopeptides, containing a reduced peptide bond between residues 6 and 7 (Psi(6-7)), displayed very similar properties of binding to major histocompatibility complex (MHC) and recognition by T cell receptor transgenic T cells specific for GP33 when compared with the parent peptide. We assessed in vitro and in vivo the proteolytic resistance of GP33 and Psi(6-7) and analyzed its contribution to the priming properties of these peptides. The Psi(6-7) analogue exhibited a dramatically increased proteolytic resistance when compared with GP33, and we show for the first time that MHC-peptide complexes formed in vivo with a pseudopeptide display a sustained half-life compared with the complexes formed with the natural peptide. Furthermore, in contrast to immunizations with GP33, three injections of Psi(6-7) in saline induced significant antiviral protection in mice. The enhanced ability of Psi(6-7) to induce antiviral protection may result from the higher stability of the analogue and/or of the MHC-analogue complexes.  (+info)

Disproportionate recruitment of CD8+ T cells into the central nervous system by professional antigen-presenting cells. (5/13590)

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)

N,N'-Diacetyl-L-cystine-the disulfide dimer of N-acetylcysteine-is a potent modulator of contact sensitivity/delayed type hypersensitivity reactions in rodents. (6/13590)

Oral N-acetyl-L-cysteine (NAC) is used clinically for treatment of chronic obstructive pulmonary disease. NAC is easily oxidized to its disulfide. We show here that N,N'-diacetyl-L-cystine (DiNAC) is a potent modulator of contact sensitivity (CS)/delayed type hypersensitivity (DTH) reactions in rodents. Oral treatment of BALB/c mice with 0.003 to 30 micromol/kg DiNAC leads to enhancement of a CS reaction to oxazolone; DiNAC is 100 to 1000 times more potent than NAC in this respect, indicating that it does not act as a prodrug of NAC. Structure-activity studies suggest that a stereochemically-defined disulfide element is needed for activity. The DiNAC-induced enhancement of the CS reaction is counteracted by simultaneous NAC-treatment; in contrast, the CS reaction is even more enhanced in animals treated with DiNAC together with the glutathione-depleting agent buthionine sulfoximine. These data suggest that DiNAC acts via redox processes. Immunohistochemically, ear specimens from oxazolone-sensitized and -challenged BALB/c mice treated with DiNAC display increased numbers of CD8(+) cells. DiNAC treatment augments the CS reaction also when fluorescein isothiocyanate is used as a sensitizer in BALB/c mice; this is a purported TH2 type of response. However, when dinitrofluorobenzene is used as a sensitizer, inducing a purported TH1 type of response, DiNAC treatment reduces the reaction. Treatment with DiNAC also reduces a DTH footpad-swelling reaction to methylated BSA. Collectively, these data indicate that DiNAC in vivo acts as a potent and effective immunomodulator that can either enhance or reduce the CS or DTH response depending on the experimental conditions.  (+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. (7/13590)

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)

Phenotypic and functional characterization of CD8(+) T cell clones specific for a mouse cytomegalovirus epitope. (8/13590)

A series of CD8(+) T cell clones, specific for the IE1 epitope YPHFMPTNL, of the immediate-early protein 1 of the murine cytomegalovirus (MCMV) were generated in order to determine their protective activity against this infection and correlate their phenotypic markers with antiviral activity. We found that the adoptive transfer of three of these anti-MCMV CD8(+) T cell clones into irradiated naive mice resulted in protection against challenge, while another CD8(+) T cell clone, of the same specificity, failed to confer protection. The clones that conferred protection against lethal challenge reduced greatly viral replication in the lung and other organs of the mice. Using one of the protective anti-MCMV CD8(+) T cell clones we found that in order to be fully protective the cells had to be transferred to recipient mice no later than 1 day after MCMV challenge. The adoptive transfer of these CD8(+) T cell clones also protected CD4(+) T-cell-depleted mice. Phenotypic characterization of the anti-MCMV clones revealed that the nonprotective clone expressed very low levels of CD8 molecules and produced only small amounts of TNF-alpha upon antigenic stimulation. Most importantly, our current study demonstrates that this MHC class I-restricted IE1 epitope of MCMV is efficiently presented to CD8(+) T cell clones in vivo and further strengthens the possibility of the potential use of CD8(+) T cell clones as immunotherapeutic tools against cytomegalovirus-induced disease.  (+info)

*Nc/Nga mice model

This infiltrate consists mainly of CD4 positive T lymphocytes with less CD8 positive lymphocytes and macrophages. Infiltration ... All these genes or their products more precisely are involved in T lymphocytes development. Derm1 region is conserved on human ...

*Autoimmune pancreatitis

... or CD8-positive lymphocytes and IgG4-positive plasma cells, and exhibits interstitial fibrosis and acinar cell atrophy in later ... It has been proposed that a cytologic smear primarily composed of acini rich in chronic inflammatory cells (lymphocytes, plasma ... Histopathologic examination of the pancreas shows fibrotic changes with lymphocyte and plasma cell infiltrate. For diagnosis, ...

*IRF1

Homozygous mutant animals had abnormal peripheral blood lymphocytes, specifically decreased CD8-positive T cell and NK cell ... numbers and an increase in CD4-positive T cells. The mice also had an abnormal integument phenotype determined by a study of ...

*Xanthogranulomatous inflammation

Many T lymphocytes were identified by these authors positive to CD4 and CD8. Macrophages and T lymphocytes demonstrated a ... The foam cells of monocyte/macrophage origin are positive for KP1, HAM56, CD11b and CD68 as pointed out by Nakashiro et al. in ... Under microscope, the cellular infiltrate includes neutrophils, lymphocytes, plasma cells, erythrocytes, hemosiderin-laden ...

*List of MeSH codes (A11)

... cd8-positive t-lymphocytes MeSH A11.118.637.555.567.569.220.200 - t-lymphocytes, cytotoxic MeSH A11.118.637.555.567.569.500 - t ... cd4-positive t-lymphocytes MeSH A11.118.637.555.567.569.200.400 - t-lymphocytes, helper-inducer MeSH A11.118.637.555.567.569. ... b-lymphocyte subsets MeSH A11.118.637.555.567.550.500 - t-lymphocyte subsets MeSH A11.118.637.555.567.562 - b-lymphocytes MeSH ... lymphocyte subsets MeSH A11.118.637.555.567.622 - lymphocytes, null MeSH A11.118.637.555.567.650 - lymphocytes, tumor- ...

*List of MeSH codes (A15)

... cd8-positive t-lymphocytes MeSH A15.145.229.637.555.567.569.220.200 --- t-lymphocytes, cytotoxic MeSH A15.145.229.637.555.567. ... t-lymphocytes, regulatory MeSH A15.382.490.555.567.569.220 --- cd8-positive t-lymphocytes MeSH A15.382.490.555.567.569.220.200 ... cd4-positive t-lymphocytes MeSH A15.382.490.555.567.569.200.400 --- t-lymphocytes, helper-inducer MeSH A15.382.490.555.567.569. ... t-lymphocytes MeSH A15.145.229.637.555.567.569.200 --- cd4-positive t-lymphocytes MeSH A15.145.229.637.555.567.569.200.400 --- ...

*Avian reovirus

The most activity was observed during the subacute phase with an increase in CD8 and CD4 lymphocytes. At this phase, clusters ... During the chronic phase, a high amount of CD4 T- cells and a few IgM-positive B-cells were observed. Immunosuppression ... Within the synovium collected, plasma cells and T-lymphocytes were the primary inflammatory cells present. During the acute- ... and T and B-lymphocytes were observed to determine its effects on cellular infiltrates during the development of reovirus ...

*Helper/suppressor ratio

CD8 ratio) is a basic laboratory test in which the percentage of CD3-positive lymphocytes in the blood positive for CD4 (T ... production of HIV specific CD8 positive cells will cause a large fall in the ratio, but subsequent immunosuppression over time ... Normal values (95% confidence intervals) are approximately 30-60% CD4 and 10-30% CD8 depending on age (ratio 0.9 to 3.7 in ... The T-Lymphocyte Helper/Suppressor Profile (Helper/Suppressor ratio, T4:T8 ratio, CD4: ...

*Hypereosinophilia

CD7 positive T cells, CD3 negative, CD4 positive T cells, or CD3 positive, CD4 negative, CD8 negative T cells) and is thought ... In on study of 16 lymphocyte-variant hypereosinophilia patients with the aberrant CD3 negative, CD41 positive immunophenotype, ... in T-cells or the proliferation of lymphocytes with the CD3 negative, CD41 positive immunophenotype may occur during the ... Lymphocyte-variant hypereosinophilia is a disorder attributed to the expansion of a cytokine-producing, aberrant population of ...

*Thymocyte

... positive for both CD4 and CD8). The final stage in maturation is the single positive stage (positive for either CD4 or CD8). In ... Thymopoiesis is the process in the thymus by which thymocytes differentiate into mature T lymphocytes. The primary function of ... At this stage thymocytes upregulate both CD4 and CD8, becoming double positive cells. Double positive thymocytes that have a T ... Expression of both CD4 and CD8 makes them double positive, and matures into either CD4+ or CD8+ cells. Thymocytes are ...

*T-cell prolymphocytic leukemia

T-PLL has the immunophenotype of a mature (post-thymic) T-lymphocyte, and the neoplastic cells are typically positive for pan-T ... The immunophenotype CD4+/CD8- is present in 60% of cases, the CD4+/CD8+ immunophenotype is present in 25%, and the CD4-/CD8+ ... A high lymphocyte count (> 100 x 109/L) along with low amounts of red blood cells and platelets in the blood are common ... In the peripheral blood, T-PLL consists of medium-sized lymphocytes with single nucleoli and basophilic cytoplasm with ...

*Human leukocyte antigen

... also called CD8 positive- or cytotoxic T-cells) that destroy cells. MHC class I proteins associate with β2-microglobulin, which ... HLAs corresponding to MHC class II (DP, DM, DOA, DOB, DQ, and DR) present antigens from outside of the cell to T-lymphocytes. ... A representative cellular assay is the mixed lymphocyte culture (MLC) and used to determine the HLA class II types. The ... These particular antigens stimulate the multiplication of T-helper cells (also called CD4 positive T cells), which in turn ...

*Autoimmune lymphoproliferative syndrome

... for ALPS Mild elevations also found in other autoimmune diseases Thought to be cytotoxic T lymphocytes that have lost CD8 ... Can have antibodies to blood cells (DAT, anti-neutrophil, anti-platelet). Also, can have positive ANA, RF, ANCA Defective in ... It affects lymphocyte apoptosis. It is a RASopathy. It is a rare genetic disorder of abnormal lymphocyte survival caused by ... Sirolimus may not be as immune suppressive in normal lymphocytes as other agents. Some patients have had improvement in immune ...

*McDonald criteria

... and different lymphocyte subtypes, reacting to CD3, CD4, CD8, CD20 and CD138. The sensitivity of McDonald criteria is low with ... In order to reduce false positives, McDonald et al. propose that their criteria should be applied only after any other disease ... ", "dissemination" and a "positive MRI", etc. Later they were revised again in 2010. McDonald's criteria are the standard ...

*ZAP70

CLL that is positive for the marker ZAP-70 has an average survival of 8 years. CLL that is negative for ZAP-70 has an average ... T lymphocytes are activated by engagement of the T cell receptor with processed antigen fragments presented by professional ... Upon this activation, the TCR co-receptor CD4 or CD8 binds to the MHC, activating the co-receptor associated tyrosine kinase ... "Differential Requirements for Src-Family Kinases in SYK or ZAP70-Mediated SLP-76 Phosphorylation in Lymphocytes". Frontiers in ...

*Harald von Boehmer

... has studied the role of T lymphocytes in the immune system. In particular he has addressed the contribution ... Questions concerned with the role of positive and negative selection of developing T cells by peptide-MHC complexes in the ... Nature 261, 141 (1976). Allo-MHC-restricted CD4 and CD8 T cells in hemopoietic chimeras reveal plasticity of MHC-restricted ... Harald von Boehmer (born November 30, 1942) is a German/Swiss immunologist best known for his work on T lymphocytes. The ...

*Large granular lymphocytic leukemia

"Clonal expansion of lymphocytes bearing the gamma delta T-cell receptor in a patient with large granular lymphocyte disorder". ... Immunohistochemistry for perforin, TIA-1, and granzyme B are usually positive. Clonal rearrangements of the T-cell receptor ( ... are transformed CD8+ T-cell with clonal rearrangements of β chain T-cell receptor genes for the majority of cases and a CD8- T- ... The neoplastic lymphocytes seen in this disease are large in size with azurophilic granules that contains proteins involved in ...

*RBBP7

... hemizygous mutant males had decreased CD4-positive and CD8-positive T cell numbers. RBBP7 has been shown to interact with: ... ". "Peripheral blood lymphocytes data for Rbbp7". Wellcome Trust Sanger Institute. [dead link] Gerdin AK (2010). "The Sanger ...

*T cell

For example, miR-181a was found to play a role in the positive selection of T lymphocytes. The thymus contributes fewer cells ... These thymocytes will then express both CD4 and CD8 and progresses to the double positive (DP) stage where selection of the α- ... If the cell does not lose its signal, it will continue downregulating CD8 and become a CD4+, single positive cell. But, if ... A T cell, or T lymphocyte, is a type of lymphocyte (a subtype of white blood cell) that plays a central role in cell-mediated ...

*Postpartum thyroiditis

Women who test positive for thyroid antibodies may be at increased risk of developing symptoms associated with postpartum ... CD8 ratio) TSH-receptor antibodies (TSH-R Abs) This condition is commonly undiagnosed by physicians due to either unfamiliarity ... increase in TPOAb subclasses IgG1-IgG3 lymphocyte infiltration and follicle formation within thyroid gland (Hashimoto's ...

*MHC restriction

This is called positive selection. During positive selection, co-receptors CD4 and CD8 initiate a signaling cascade following ... When primary lymphocytes are developing and differentiating in the thymus or bone marrow, T cells die by apoptosis if they ... It follows that MHC restriction is imposed by CD4 and CD8 co-receptors during positive selection of T cell selection. A ... T cell maturation involves two distinct developmental stages: positive selection and negative selection. Positive selection ...

*ARL4D

Homozygous mutant females had decreased bone mineral content, heart weight, lean body mass and CD8-positive, alpha-beta memory ... "Peripheral blood lymphocytes data for Arl4d". Wellcome Trust Sanger Institute. "Heart weight data for Arl4d". Wellcome Trust ... "Recognition of ADP-ribosylation factor 4-like by HLA-A2-restricted and tumor-reactive cytotoxic T lymphocytes from patients ...

*Angioimmunoblastic T-cell lymphoma

The polymorphous infiltrate consists of lymphocytes of moderate size with pale/clear cytoplasm and smaller reactive lymphocytes ... AITL typically has the phenotype of a mixture of CD4+ and CD8+ T-cells, with a CD4:CD8 ratio greater than unity. Polyclonal ... and positive rheumatoid factor. The normal architecture of a lymph node is partially effaced by a polymorphous infiltrate and ...

*Munir Pirmohamed

... fever and positive lymphocyte transformation test in a patient on irbesartan". The British Journal of Dermatology. 155 (2): 491 ... CD8(+), and CD4(+)CD8(+) T-cell clones from patients with carbamazopine hypersensitivity Herbal medicines and acute medical ... fever and positive lymphocyte transformation test in a patient on irbesartan Serious carbamazepine-induced hypersensitivity ... Owen, A; Goldring, C; Morgan, P; Park, BK; Pirmohamed, M (August 2006). "Induction of P-glycoprotein in lymphocytes by ...

*Major histocompatibility complex

Antigen presentation: MHC molecules bind to both T cell receptor and CD4/CD8 co-receptors on T lymphocytes, and the antigen ... MHC restriction occurs during lymphocyte development in the thymus through a process known as positive selection. T cells that ... This means in contrast to CD8/TCR interaction that activates Tc lymphocytes, NK cells becomes deactivated when bound to MHC I. ... It presents epitopes to killer T cells, also called cytotoxic T lymphocytes (CTLs). A CTL expresses CD8 receptors, in addition ...

*GNLY

2003). "CD8 T cell-mediated killing of Cryptococcus neoformans requires granulysin and is dependent on CD4 T cells and IL-15". ... Granulysin is present in cytolytic granules of cytotoxic T lymphocytes (CTL) and natural killer (NK) cells. Granulysin is made ... Recombinant 9 kD granulysin is broadly cytolytic against tumors and microbes, including gram positive and gram negative ... Donlon TA, Krensky AM, Clayberger C (1990). "Localization of the human T lymphocyte activation gene 519 (D2S69E) to chromosome ...
The results presented herein suggest that generation of an effective influenza-specific CD8 T cell response requires activated CD8 T cells to interact with pulmonary pDCs, CD8α+ DCs, or iDCs in a MHC class I-, viral epitope-dependent manner once they enter the lungs. This secondary interaction is in addition to the initial DC-T cell interactions that occur in the LN during activation of naive CD8 T cells. To our knowledge, this is the first study detailing a critical role for peripheral DC-CD8 T cell interactions after initial programming of primary effector T cells in the LN. This suggests that the influenza-specific CD8 T cell response may be regulated by a "two-hit" model of development and that the magnitude, and possibly phenotype, of the peripheral CD8 T cells generated may be related to both the initial programming that occurs in the LN, but also by secondary contacts with DC subsets at the site of the infection. Of note, we have observed differential magnitudes of recruitment into the ...
p286/I-Ag7 tetramer-positive CD4+ T cells from G286 mice delay diabetes transfer. Tetramer-positive and -negative cells were sorted from G286 lymph node cells w
We show here that HCV-specific CD8+ T cells can be frequently detected in HCV-seronegative (HCV-SN) individuals and that these cells may impact the response to vaccination. Virus-specific T cell responses in unexposed individuals have been reported before in several settings (15, 16, 19, 32), and the composition of this preexisting T cell repertoire may influence the response toward vaccines, as suggested by reports for other infections (14, 33). However, thus far, no study has systematically studied the frequency and repertoire of HCV-specific CD8+ T cell responses in a large number of HCV-SN individuals and investigated how preexisting HCV-specific CD8+ T cells may influence vaccine responses. Our study, which included a total of 121 HCV-SNs, revealed a high prevalence of HCV NS3-1073-specific CD8+ T cell responses both ex vivo, as well as in vitro in about one-third of individuals tested, whereas the NS3-1073-specific T cell responses were low or absent in the remaining two-thirds. However, ...
Influenza A virus remains a major threat to public health, and the inactivated split-virus vaccine is the most prevalent vaccine used worldwide. However, our knowledge about cellular immune responses to the inactivated influenza virus vaccine and its correlation with humoral responses are yet limited, which has restricted our understanding of the vaccines protective mechanisms. Herein, in two clinical trials, T-cell responses specific for both previously identified human leucocyte antigen (HLA)-I-restricted epitopes from influenza virus and hemagglutinin (HA) protein were longitudinally investigated before, during, and after a two-dose vaccination with the inactivated 2009 pandemic H1N1 (2009-pH1N1) vaccine. A robust antibody response in all of the donors after vaccination was observed. Though no CD8(+) T-cell responses to known epitopes were detected, HA-specific T-cell responses were primed following vaccination, and the responses were found to be mainly CD4(+) T-cell dependent. However, ...
T cell responses play an important role in the outcome of HBV and HCV infection, e.g. viral elimination versus persistence. However, multiple mechanisms can lead to the failure of the virus-specific T cell response. These mechanisms include primary T cell failure, T cell exhaustion, the emergence of viral escape mutants, as well as T cell dysfunction. Furthermore, genetic factors such as the individual HLA allele background play an important role in the outcome of infection. Once viral persistence has been established, HBV or HCV infection can progress to liver fibrosis and cirrhosis with an enhanced risk for HCC. Tumor-specific T cells (e.g. AFP-specific T cells) are thought to contribute to cancer control.. The focus of our group is the identification and characterization of virus-specific CD4+ and CD8+ T cell responses during acute and chronic HBV and HCV infection with a special focus on intrahepatic T cell responses as well as the mechanisms of viral persistence (e.g., viral escape, T cell ...
Autoreactive CD8 T cells play a central role in the destruction of pancreatic islet β-cells that leads to type 1 diabetes, yet the key features of this immune-mediated process remain poorly defined. In this study, we combined high-definition polychromatic flow cytometry with ultrasensitive peptide-human leukocyte antigen class I tetramer staining to quantify and characterize β-cell-specific CD8 T cell populations in patients with recent-onset type 1 diabetes and healthy control subjects. Remarkably, we found that β-cell-specific CD8 T cell frequencies in peripheral blood were similar between subject groups. In contrast to healthy control subjects, however, patients with newly diagnosed type 1 diabetes displayed hallmarks of antigen-driven expansion uniquely within the β-cell-specific CD8 T cell compartment. Molecular analysis of selected β-cell-specific CD8 T cell populations further revealed highly skewed oligoclonal T cell receptor repertoires comprising exclusively private clonotypes. ...
T cell exhaustion is a major factor in failed pathogen clearance during chronic viral infections. Immunoregulatory pathways, such as PD-1 and IL-10, are upregulated upon this ongoing antigen exposure and contribute to loss of proliferation, reduced cytolytic function, and impaired cytokine production by CD4 and CD8 T cells. In the murine model of LCMV infection, administration of blocking antibodies against these two pathways augmented T cell responses. However, there is currently no in vitro assay to measure the impact of such blockade on cytokine secretion in cells from human samples. Our protocol and experimental approach enable us to accurately and efficiently quantify the restoration of cytokine production by HIV-specific CD4 T cells from HIV infected subjects. Here, we depict an in vitro experimental design that enables measurements of cytokine secretion by HIV-specific CD4 T cells and their impact on other cell subsets. CD8 T cells were depleted from whole blood and remaining PBMCs were ...
Improving adaptive anti-viral responses: a key to eliminating persistent viral infection. HCMV establishes a persistent infection, and although in a healthy subject infection is generally asymptomatic, infection of immunocompromised hosts leads to severe disease. Using the MCMV-infection model, recent studies have shown that MCMV-susceptible and MCMV-resistant mouse strains have functional differences in the efficacy of the antiviral CD4+ and CD8+ T cell responses and in the ability to control persistent virus. These studies provided evidence to indicate that antiviral T cell responses are negatively affected by natural killer (NK) cells. Our data indicate that the NK cell-mediated elimination of virus-infected dendritic cells (DC) may be the key event in this process. Ongoing studies will address how T cells control persistent infection and how their anti-viral activity can be restored therapeutically. This research will help us understand viral pathogenesis and importantly will provide ...
This thesis focuses on the decision making in the most common business form: family businesses. A well-established theoretical model within the family business field is The three circle-model, which is based on three different dimensions: family, ownership and business. Most of the family businesses stay small but the ones expanding face the dilemma of balancing the best development of the dimensions. However, these three dimensions can contradict each other and as a result the founders are forced to choose which of the dimensions to prioritize when taking decisions.The purpose of this thesis is to create an understanding of how the family, the ownership and the business dimensions affect founders thoughts and reasoning behind decisions in the expansion phase in first generation family firms with few owners.We have reached the conclusions with a qualitative approach using case studies. We have gathered the empirical data by using Life story and Critical incident to define expansion decisions in ...
Sergeev, V.A. and Kubyshkina, M.V. and Baumjohann, W. and Nakamura, R. and Amm, O. and Pulkkinen, T. and Angelopoulos, V. and Mende, S.B. and Klecker, B. and Nagai, T. and Sauvaud, J.-A. and Slavin, J.A. and Thomsen, M.F. (2005) Transition from substorm growth to substorm expansion phase as observed with a radial configuration of ISTP and Cluster spacecraft. Annales Geophysicae, 23 (6). pp. 2183-2198. ISSN 0992-7689 ...
Abstract In a human melanoma model of tumor antigen (TA)-based immunization, we tested the functional status of TA-specific CD8+ cytotoxic T lymphocytes. A quiescent phenotype lacking direct ex vivo cytotoxic and proliferative potential was identified that was further characterized by comparing its transcriptional profile to that of TA-specific T cells sensitized in vitro by exposure to the same TA and the T-cell growth factor interleukin 2 (IL-2). Quiescent circulating tumor-specific CD8+ T cells were deficient in expression of genes associated with T-cell activation, proliferation, and effector function. This quiescent status may explain the observed lack of correlation between the presence of circulating immunization-induced lymphocytes and tumor regression. In addition, the activation of TA-specific T cells by in vitro antigen recall and IL-2 suggests that a complete effector phenotype might be reinstated in vivo to fulfill the potential of anticancer vaccine protocols.. ...
T cells play pivotal roles in shaping host immune responses in infectious diseases, autoimmunity and cancer. The activation of T cells requires immune and growth factor-derived signals. However, alterations in nutrients and metabolic signals tune T cell responses by impinging upon T cell fates and immune functions. In this review, we summarize how key nutrients, including glucose, amino acids and lipids, and their sensors and transporters shape T cell responses. We also briefly discuss regulation of T cell responses by oxygen and energy sensing mechanisms.
As the central player in the immune response fighting against pathogen invasions in mammals, the activation of T cells must be tightly regulated. Proper resolution of a T cell response is as essential as its initiation because of the possible severe pathological consequences of a hyperinflammatory response. NF-κB activation is a key signaling event downstream of TCR engagement and regulates almost all of the important aspects of T cell activation. Because of its pivotal role, NF-κB activation in T cells is regulated through a multilayered negative regulatory network (Schulze-Luehrmann and Ghosh, 2006). In this study, we identified miR-146a as an important new member of the negative feedback loop that modulates TCR signaling to NF-κB and demonstrated its physiological role in regulating both acute T cell response and chronic hyperinflammatory autoimmune T cell response in vivo. Based on these results, we propose a model of miR-146a as an important new constituent of the negative feedback ...
Spleen 3 days after immunisation. B cells (red), CTL (green) and dendritic cells (blue I noted some time ago that, despite the name, its clear that cytotoxic T
The scope of the genital herpes problem is daunting. The disease-technically known as HSV-2-affects one in every six people between the ages of 14 and 49 in the United States. Worldwide infection estimates reach 500 million. An approved vaccine would have the potential to impact patients on so many levels, says Darren Higgins, co-founder of…
These kits utilize a patented technique for exchanging up to ten peptides on an MHC class I tetramer. Components for quantifying the extent of peptide exchange by flow cytometry are included ...
Researchers have discovered that an important part of the immune system puts up a strong anti-inflammatory T cell response following the development of atherosclerotic lesions.
A major challenge in the HIV field has been to understand why the strength of virus-specific CD8 T cell responses has no relationship to viral load, and yet CD8 depletion studies indicate that these cells are critical for immune control. And a major challenge in the field of immunology in general has been the rapid translation of advances in murine models to humans. In late 2005, through a telephone conversation with Rafi Ahmed, we became aware of yet unpublished data in the mouse model of chronic infection. His laboratory had shown that in mice persistently infected with LCMV, T cells up-regulate a surface molecule termed PD-1, for programmed death-1, a negative immunoregulatory molecule that turned off CD8 T cell function. The potential parallels with HIV were immediately obvious to us-perhaps persistent exposure to HIV was having a similar impact on CD8 T cell function in humans, and perhaps similar immune regulation was rendering CD4 T cells exhausted as well.. We immediately formed a ...
The contraction phase of T cell activation is an important part of the immune response. A recent paper looks at the mechanisms involved
bricko sends this disappointing but not unexpected news from Techdirt: While it didnt get nearly as much attention as other parts of SOPA, one section in the bill that greatly concerned us was the massive expansion of the diplomatic corp.s IP attaches. If youre unfamiliar with the program, bas...
While MHC class Ia-restricted CD8 T cell responses to viral infections have been extensively characterized, little is known about MHC class Ib-restricted CD8 T cells during viral infection. Mouse polyoma virus establishes a persistent low-level infection and induces tumors in MHC class Ia + class Ib deficient (i.e., b2m−/−) mice. Unexpectedly, mice selectively deficient for MHC class Ia molecules (i.e., Kb−/−Db−/−) mice efficiently control polyoma viral replication and are resistant to polyoma virus-induced tumors. Polyoma virus-specific CD8 T cell cloned lines were isolated from immune Kb−/−Db−/− mice. Using these cloned lines, we mapped their MHC restriction to H2-Q9, an MHC Class Ib molecule of the Qa-2 family. We identified the Q9-restricted viral epitope as a 9mer peptide from a viral capsid protein. In preliminary studies, we found that the magnitude of the Q9-restricted antiviral CD8 T cell response progressively inflates over the course of infection. Experiments are ...
Peptide-major histocompatibility complex (p-MHC) class I tetramer complexes have facilitated the early detection and functional characterisation of epitope specific CD8+ cytotoxic T lymphocytes (CTL). Here, we report on the generation of seven recombinant bovine leukocyte antigens (BoLA) and recombinant bovine β2-microglobulin from which p-MHC class I tetramers can be derived in ~48 h. We validated a set of p-MHC class I tetramers against a panel of CTL lines specific to seven epitopes on five different antigens of Theileria parva, a protozoan pathogen causing the lethal bovine disease East Coast fever. One of the p-MHC class I tetramers was tested in ex vivo assays and we detected T. parva specific CTL in peripheral blood of cattle at day 15-17 post-immunization with a live parasite vaccine. The algorithm NetMHCpan predicted alternative epitope sequences for some of the T. parva CTL epitopes. Using an ELISA assay to measure peptide-BoLA monomer formation and p-MHC class I tetramers of new ...
The primary goal of this study was to resolve the uncertainty about whether HESNs make T cell responses to HIV-1. We compared the frequencies of HIV-1-specific T cell responses over time between HESN and HUSN groups in a powered, blind study with independent data analysis. In these donors, no T cell responses were detectable without culture, except, notably, in an HESN participant who was homozygous for CCR5Δ32 and therefore genetically resistant to HIV-1 infection (18, 46). Using the more sensitive cultured ELISpot assay, T cell responses were found in both HESNs and HUSNs. Significant differences were found in the frequencies of T cell responses over time, with HESNs more likely to have positive T cell responses than HUSNs. HESNs more often maintained HIV-1-specific T cell responses across visits than HUSNs. Also, among positive responders, T cell responses were of significantly higher magnitude in HESNs than in HUSNs. Given that the cultured ELISpot assay expands antigen-specific cells ...
How vaccines control the development of antigen-specific effector and memory T helper cells is central to protective immunity but remains poorly understood. Here we found that protein vaccination selected high-affinity, CXCR5+ICOS(hi) follicular B-helper T cells (T(FH) cells) that developed in draining lymphoid tissue to regulate B cell responses. In the memory phase, reservoirs of antigen-specific CXCR5+ICOS(lo) T(FH) cells persisted with less effector activity but accelerated antigen-recall ability. This new compartment of memory T(FH) cells was retained in draining lymphoid sites with antigen-specific memory B cells, persistent complexes of peptide and major histocompatibility complex class II and continued expression of CD69. Thus, protein vaccination promotes B cell immunity by selecting high-affinity effector T(FH) cells and creating lymphoid reservoirs of antigen-specific memory T(FH) cells in vivo ...
T lymphocytes play a primary role in recovery from viral infections and in antiviral immunity. Although viral-specific CD8+ and CD4+ T cells have been shown to be able to lyse virally infected targets in vitro and promote recovery from lethal infection in vivo, the role of CD4+ T lymphocytes and their mechanism(s) of action in viral immunity are not well understood. The ability to further dissect the role that CD4+ T cells play in the immune response to a number of pathogens has been greatly enhanced by evidence for more extensive heterogeneity among the CD4+ T lymphocytes. To further examine the role of CD4+ T cells in the immune response to influenza infection, we have generated influenza virus-specific CD4+ T cell clones from influenza-primed BALB/c mice with differential cytokine secretion profiles that are defined as T helper type 1 (Th1) clones by the production of interleukin 2 (IL-2) and interferon gamma (IFN-gamma), or as Th2 clones by the production of IL-4, IL-5, and IL-10. Our ...
What are the decisive factors that determine which effector cells survive to become long-lived memory cells and which cells die during the contraction phase? We have characterized the transcriptome of effector and memory T cells and identified genetic pathways and several transcription factors that regulate this life or death decision in activated T cells. Our work has helped to outline a model of effector T cell differentiation wherein a small subset of T cells develop into memory precursor cells that are more fit to persist following the first infection than the majority of effector cells. These memory precursor cells develop into long-lived memory T cells that protect against re-infection. Several types of memory T cells, which differ by their phenotypes, functions and anatomical locations, are produced to create a sophisticated, multi-layered defense system. Conceptually, the memory T cells are divided into three subsets: (1) Tissue resident memory T (TRM) cells, which locally reside in ...
The original study of EBV-specific CD8+ responses with HLA class I tetramers was the first to show definitively that Ag-experienced CD8+ T cells in man could be phenotypically heterogeneous in terms of CD45RO vs RA expression and in terms of CD28 status (3). The present work was prompted by our observation that these tetramer-staining CD8+ populations also appeared functionally heterogeneous, in that only 20-40% of tetramer-positive cell numbers were detected in ELISPOT assays of peptide-induced IFN-γ release (21). Our aim was to readdress the much discussed relationship between CD8+ T cell phenotype, type I cytokine production, and cytotoxic capacity (7, 8, 10, 11, 12, 31) with assays specific for the cognate epitope rather than the nonspecific assays (PMA/ionomycin stimulation and anti-CD3 redirected cytotoxicity respectively) that had been used to date. As others have reported (22, 33), we found that staining for the tetramer, CD8, and a third surface marker of choice could be combined with ...
BACKGROUND: The relative immunogenicity of human immunodeficiency virus type 1 (HIV-1) proteins for CD8+ and CD4+ cell responses has not been defined. METHODS: HIV-1-specific T cell responses were evaluated in 65 chronically HIV-1-infected untreated subjects by interferon- gamma flow cytometry with peptides spanning the clade C consensus sequence. RESULTS: The magnitude of HIV-1-specific CD8+ T cell responses correlated significantly with CD4+ cell responses, but the percentage of CD8+ T cells directed against HIV-1 (median, 2.76%) was always greater than that of CD4+ cells (median, 0.24%). Although CD8+ T cell responses were equally distributed among Gag, Pol, and the regulatory and accessory proteins, Gag was the dominant target for CD4+ cell responses. There was no consistent relationship between virus-specific CD8+ or CD4+ cell response and viral load. However, the median viral load in subjects in whom Gag was the dominant CD8+ T cell target was significantly lower than that in subjects in whom non
Purpose: NY-ESO-1 (ESO), a tumor specific antigen of the Cancer/Testis group, is presently viewed as an important model antigen for the development of generic anti-cancer vaccines. The ESO119-143 region is immunodominant following immunization with a recombinant ESO vaccine. In this study, we have generate DRB1*0101/ESO119-143 tetramers and used them to assess CD4 T cell responses in vaccinated patients expressing DR1. Experimental design: We generated tetramers of DRB1*0101 incorporating peptide ESO119-143 using a previously described strategy. We assessed ESO119-143 specific CD4 T cells in peptide-stimulated post-vaccine cultures using the tetramers. We isolated DR1/ESO119-143 tetramer+ cells by cell sorting and characterized them functionally. We assessed vaccine-induced CD4+ DR1/ESO119-143 tetramer+ T cells ex vivo and characterized them phenotypically. Results: Staining of cultures from vaccinated patients with DR1/ESO119-143 tetramers identified vaccine-induced CD4 T cells. Tetramer+ cells ...
Purpose: NY-ESO-1 (ESO), a tumor-specific antigen of the cancer/testis group, is presently viewed as an important model antigen for the development of generic anticancer vaccines. The ESO119-143 region is immunodominant following immunization with a recombinant ESO vaccine. In this study, we generated DRB1*0101/ESO119-143 tetramers and used them to assess CD4 T-cell responses in vaccinated patients expressing DRB1*0101 (DR1).. Experimental Design: We generated tetramers of DRB1*0101 incorporating peptide ESO119-143 using a previously described strategy. We assessed ESO119-143-specific CD4 T cells in peptide-stimulated postvaccine cultures using the tetramers. We isolated DR1/ESO119-143 tetramer+ cells by cell sorting and characterized them functionally. We assessed vaccine-induced CD4+ DR1/ESO119-143 tetramer+ T cells ex vivo and characterized them phenotypically.. Results: Staining of cultures from vaccinated patients with DR1/ESO119-143 tetramers identified vaccine-induced CD4 T cells. ...
The adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL) or TCR-redirected peripheral blood lymphocytes (PBL) is a promising treatment for patients with metastatic cancer (48, 49). The experiments described in this report show that small numbers of tumor antigen-specific CD8+ T cells engineered to produce high levels of IL-12 can lead to the regression of large vascularized tumors without the need for exogenous IL-2 or vaccine in lymphodepleted hosts. The marked improvement in treatment was associated with an increase in tumor infiltration by adoptively transferred T cells, along with an increase in endogenous NK cells and endogenous CD8+ T cells from the reconstituting host. Based on the delayed kinetics of tumor destruction, modulation of endogenous host immune cells likely plays an important role in facilitating tumor destruction, but the effect of host NK cells and CD8+ T cells remains unclear.. Nevertheless, one of our key findings in this study included isolating ...
Due to an increase in its expression following the activation of B-cells and T-cells, CD44 can serve as a valuable marker for memory cells. Furthermore, the upregulation of CD44 expression is sustained on effector cells and memory cells after the immune response has subsided, so CD44 expression can also be used as an indicator of prior exposure to an antigen. However, little is currently known about its function of T cells. Recent studies have suggested that the CD44 signaling pathway may be involved in ensuring proper T cell effector responses by providing contextual signals at various anatomical sites. CD44 ligation may also promote T cell survival through the augmentation of T cell activation in response to an antigen. Studies also suggest that CD44 may contribute to both the regulation of the contraction phase of an immune response and the maintenance of immune tolerance. Furthermore, CD44 may play a role in ensuring the functional fitness of memory T cells once the memory stage has been ...
of research plan for MERIT extension. Memory T cell populations with a history of repeated antigen exposure will be generated in humans due to recurring infecti...
Inflammatory reactions are believed to be triggered by innate signals and have a major protective role by recruiting innate immunity cells, favoring lymphocyte activation and differentiation, and thus contributing to the sequestration and elimination of the injurious stimuli. Although certain lymphocyte types such as TH17 cells co-participate in inflammatory reactions, their generation from the naïve pool requires the pre-existence of an inflammatory milieu. In this context, inflammation is always regarded as beginning with an innate response that may be eventually perpetuated and amplified by certain lymphocyte types. In contrast, we here show that even in sterile immunizations or in MyD88 deficient mice, CD8 T cells produce a burst of pro-inflammatory cytokines and chemokines. These functions follow opposite rules to the classic CD8 effector functions since they are generated prior to cell expansion and decline before antigen elimination. As few as 56 CD8+ inflammatory effector cells in a lymph node
A novel clinical-grade CD40L reagent was developed to test the hypothesis that immunization with functionally mature IL-12p70-producing DCs elicits effective CD8+ T immunity in patients with newly diagnosed advanced melanoma. Immunological responses to the gp100 antigen were observed in 6 of the 7 treated patients, while clinical response (as defined by RECIST criteria) was observed in 3 of 7 patients. Importantly, IL-12p70 levels produced by patient-derived CD40L/IFN-γ-activated mDCs as well as the development of antitumor Tc1 CD8+ T cell immunity correlated with TTP. Impairment in IL-12p70 production by CD40L/IFN-γ activated mDCs was observed in the 4 clinical nonresponder patients (all with Tc2-skewed immunity), and this deficiency resulted from impaired IL-12p35 subunit transcription. However, incorporating TLR3 and TLR8 signals with CD40L/IFN-γ activation corrected the IL-12p70 production defect in clinical nonresponder patient DCs, suggesting new ways to improve vaccine efficacy in ...
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We used flow cytometry to investigate the percentage of IL-17-expressing blood T cells ex vivo in 49 healthy controls. Nonadherent PBMCs were stained for CD3, CD4, CD8, and IL-17. No IL-17-producing T cells were detected in the absence of activation (unpublished data). Upon activation with PMA-ionomycin, the percentage of CD3-positive cells producing IL-17 ranged from 0.06 to 2% (Fig. 1, A and B). The vast majority (,90%) of IL-17-positive cells were CD4-positive and CD8-negative (unpublished data). Thus, within the general population, there is considerable interindividual variability in the numbers of IL-17-producing cells present among freshly isolated T cells activated ex vivo. This makes it difficult to assess the impact of genetic lesions on the development of IL-17-producing T cells. We tested nine patients with null mutations in IRAK4 or MYD88, whose cells were unresponsive to IL-1β (and most TLRs and other IL-1 cytokine family members). The proportion of IL-17-producing T cells was not ...
CD4+ T cells play a major role in adaptive immune responses to intracellular and extracellular microbes by regulating the functions of B cells, CD8+ T cells, an...
In order to more effectively address the expansion of type 2 diabetes worldwide, this study investigated the role that stressors and the stress response play in the development of diabetes. This study analyzed clinical ...
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The authors have demonstrated compartment differences between T cell immunity in the bronchoalveolar space and the periphery. These include a predominant presence of effector memory T cells and regulatory CD4+ T cells in BAL, and a higher percentage frequency of antigen-specific CD4+ T cells against influenza virus, S pneumoniae and M tuberculosis in BAL compared to peripheral blood. Our data has also demonstrated that HIV-infected individuals have impaired pulmonary CD4+ T cell immunity, which is characterised by lower proportions of total CD4+ T cells and impaired antigen-specific BAL CD4+ T cell response to influenza virus and M tuberculosis antigens.. Consistent with previous observations,21 we noticed that BAL CD4+ and CD8+ T cells were predominantly of effector memory phenotype irrespective of HIV status, while peripheral blood T cell phenotypes were distributed among naive, central memory, effector memory and terminal effector. Effector memory T cells migrate to the lung following antigen ...
The ligands and inhibitory receptors that regulate T cell effector functions are mostly overexpressed on tumor-infiltrating immune cells or on tumor cells in the tumor microenvironment. Therefore, targeting these ligands and receptors is relatively specific to tumors compared to normal tissues. It is within these tumor microenvironments that immune effector cells acquire inhibitory receptors, resulting in T cell dysfunction. Soluble molecules include cytokines with immunosuppressive activity, such as IL-10, transforming growth factor (TGF)-β, and IL-27, which regulate immune responses to tumor cells and induce T cell dysfunction within the tumor microenvironment [99-102]. The IL-10 pathway has been intensively studied for its role in T cell dysfunction in chronic viral infections and cancer [99, 100]. IL‑10 promotes T cell exhaustion, and IL‑10 blockade reverses T cell dysfunction during chronic viral infections [99]. Co-blockade of both IL-10 and the PD1 reverses CD8+ T cell exhaustion and ...
The pool of memory T cells is regulated by homeostatic mechanisms to persist for prolonged periods at a relatively steady overall size. Recent work has shown that two members of the common gamma chain (gammac) family of cytokines, interleukin-7 (IL-7) and IL-15, govern homeostasis of memory T cells. These two cytokines work in conjunction to support memory T-cell survival and intermittent background proliferation. Normal animals contain significant numbers of spontaneously arising memory-phenotype (MP) cells, though whether these cells are representative of true antigen-specific memory T cells is unclear. Nevertheless, it appears that the two types of memory cells do not display identical homeostatic requirements. For antigen-specific memory CD8+ T cells, IL-7 is primarily important for survival while IL-15 is crucial for their background proliferation. For memory CD4+ T cells, IL-7 has an important role, whereas the influence of IL-15 is still unclear.
TY - JOUR. T1 - Peptide epitope identification for tumor-reactive CD4 T cells. AU - Kobayashi, Hiroya. AU - Celis, Esteban. PY - 2008/4/1. Y1 - 2008/4/1. N2 - Because T lymphocytes have the capacity to recognize tumor cells, significant efforts are being devoted towards the development of T cell-based immunotherapy for cancer. Most of this work has centered in the induction of anti-tumor CD8 T cells, which exhibit cytolytic activity towards tumor cells expressing tumor-specific or tumor associated antigens. Unfortunately to this day, T cell-based immunotherapy for cancer remains suboptimal. One of the possible explanations is that these immunotherapies have ignored the role that CD4 T helper lymphocytes play in the generation and persistence of CD8 T cell responses. Thus, we believe that in order to obtain clinical benefits T cell-based immunotherapy must stimulate both CD8 and CD4 tumor-reactive T cell responses. During the past seven years our group has focused on the identification of CD4 T ...
T-bet:Eomes balance, effector function, and proliferation of cytomegalovirus-specific CD8+ T cells during primary infection differentiates the capacity for durable immune control.
Chronic allograft rejection is in part mediated by host T cells that recognize allogeneic antigens on transplanted tissue. One factor that determines the outcome of a T cell response is clonal size, while another is the effector quality. Studies of alloimmune predictors of transplant graft survival have most commonly focused on only one measure of the alloimmune response. Because differing qualities and frequencies of the allospecific T cell response may provide distinctly different information we analyzed the relationship between frequency of soluble antigen and allo-antigen specific memory IFN-g secreting CD4 and CD8 T cells, their ability to secrete IL-2, and their proliferative capacity, while accounting for cognate and bystander proliferation. The results show proliferative responses primarily reflect on IL-2 production by antigen-specific T cells, and that proliferating cells in such assays entail a considerable fraction of bystander cells. On the other hand, proliferation (and IL-2 production)
HIV-epitope-specific T cell responses are critical components of the natural immune response to HIV infection, but these cells often become dysfunctional in chronic infection. Structural diversity within the epitope-specific T cell receptor (TCR) repertoire is likely beneficial in the suppression of viral epitope variants. However, the relationship between the structural and clonotypic composition of the HIV-specific TCR repertoire, clonotypic surface and functional phenotype, and avidity for and exposure to antigen is poorly defined. Dominant and sub-dominant epitope-specific T cell clonotypes were identified and the TCR repertoire was assessed over time. Surface expression of PD-1, CD38, CD127, CD45RO, and CCR7 was measured and used to define exhaustion and memory profiles on epitope-specific T cell populations during chronic infection and after initiation of antiretroviral therapy. Dominant clonotypes in chronic infection express a surface phenotype consistent with exhaustion which is ...
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Polyfunctional CD4 or CD8 T cells are proposed to represent a correlate of immune control for persistent viruses as well as for vaccine mediated protection against infection. A well-suited methodology to study complex functional phenotypes of antiviral T cells is the combined staining of intracellular cytokines and phenotypic marker expression using polychromatic flow cytometry. In this study we analyzed the effect of an overnight resting period at 37°C on the quantity and functionality of HIV-1, EBV, CMV, HBV and HCV specific CD4 and CD8 T-cell responses in a cohort of 21 individuals. We quantified total antigen specific T cells by multimer staining and used 10-color intracellular cytokine staining (ICS) to determine IFNγ, TNFα, IL2 and MIP1β production. After an overnight resting significantly higher numbers of functionally active T cells were detectable by ICS for all tested antigen specificities, whereas the total number of antigen specific T cells determined by multimer staining remained
Additional experiments revealed that the HIV-specific CD4 T cell responses showed activity associated with cell-killing and could even destroy HIV-infected macrophages - an unusual function for CD4 T cells, which have traditionally been seen as helper cells. In addition, the researchers determined that the presence of a specific cell-death protein called granzyme A prominently distinguished HIV-specific CD4 cells of participants maintaining a lower "viral set point" from those less able to control viral levels. To validate these findings, the researchers examined a larger group of HIV-infected individuals and found that those with higher levels of granzyme A in their HIV-specific CD4 T cell response immediately after infection progressed more slowly to AIDS and did not require antiretroviral therapy as quickly as did those with lower levels of the protein. "The key baseline difference between these two groups has to do with the quality, not the quantity, of the HIV-specific CD4 T cell response," ...
Treatment of invasive adenovirus (Ad) disease in hematopoietic stem cell transplant (SCT) recipients with capsid protein hexon-specific donor T cells is under investigation. We propose that cytotoxic T cells (CTLs) targeted to the late protein hexon may be inefficient in vivo because the early Ad protein E3-19K downregulates HLA class I antigens in infected cells. In this study, CD8+ T cells targeted to highly conserved HLA A2-restricted epitopes from the early regulatory protein DNA polymerase (P-977) and late protein hexon (H-892) were compared in peripheral blood (PB) and tonsils of naturally infected adults. In tonsils, epitope-specific pentamers detected a significantly higher frequency of P-977+CD8+ T cells compared to H-892+CD8+ T cells; this trend was reversed in PB. Tonsil epitope-specific CD8+ T cells expressed IFN-γ and IL-2 but not perforin or TNF-α, whereas PB T cells were positive for IFN-γ, TNF-α, and perforin. Tonsil epitope-specific T cells expressed lymphoid homing marker CCR7 and
Many vaccination strategies and immune cell therapies aim at increasing the numbers of memory T cells reactive to protective antigens. However, the differentiation lineage and therefore the optimal generation conditions of CD4 memory cells remain controversial. Linear and divergent differentiation models have been proposed, suggesting CD4 memory T cell development from naive precursors either with or without an effector-stage intermediate, respectively. Here, we address this question by using newly available techniques for the identification and isolation of effector T cells secreting effector cytokines. In adoptive cell transfers into normal, nonlymphopenic mice, we show that long-lived virus-specific memory T cells can efficiently be generated from purified interferon gamma-secreting T helper (Th) type 1 and interleukin (IL)-4- or IL-10-secreting Th2 effectors primed in vitro or in vivo. Importantly, such effector-derived memory T cells were functional in viral challenge infections. They proliferated
Immune monitoring of T cell responses increasingly relies on the use of peptide pools. Peptides, when restricted by the same HLA allele, and presented from within the same peptide pool, can compete for HLA binding sites. What impact such competition has on functional T cell stimulation, however, is not clear. Using a model peptide pool that is comprised of 32 well-defined viral epitopes from Cytomegalovirus, Epstein-Barr virus, and Influenza viruses (CEF peptide pool), we assessed peptide competition in PBMC from 42 human subjects. The magnitude of the peptide pool-elicited CD8 T cell responses was a mean 79% and a median 77% of the sum of the CD8 T cell responses elicited by the individual peptides. Therefore, while the effect of peptide competition was evident, it was of a relatively minor magnitude. By studying the dose-response curves for individual CEF peptides, we show that several of these peptides are present in the CEF-pool at concentrations that are orders of magnitude in excess of what is
T cell dysfunction in the presence of ongoing antigen exposure is a cardinal feature of chronic viral infections with persistent high viremia, including HIV-1. Although interleukin-10 (IL-10) has been implicated as an important mediator of this T cell dysfunction, the regulation of IL-10 production in chronic HIV-1 infection remains poorly understood. We demonstrated that IL-10 is elevated in the plasma of individuals with chronic HIV-1 infection and that blockade of IL-10 signaling results in a restoration of HIV-1-specific CD4 T cell proliferation, gamma interferon (IFN-γ) secretion, and, to a lesser extent, IL-2 production. Whereas IL-10 blockade leads to restoration of IFN-γ secretion by HIV-1-specific CD4 T cells in all categories of subjects investigated, significant enhancement of IL-2 production and improved proliferation of CD4 T helper cells are restricted to viremic individuals. In peripheral blood mononuclear cells (PBMCs), this IL-10 is produced primarily by CD14(+) monocytes, but ...
OBJECTIVE: To investigate the hypothesis that clonality of synovial T cells from patients with rheumatoid arthritis is at least partly due to the presence of virus-specific T cells expressing a restricted repertoire of T cell receptors (TCRs). METHODS: Using fluorescently labeled HLA class I-peptide tetramers, populations of virus-specific CD8+ T cells were identified in samples of peripheral blood and synovial fluid taken from 4 patients with inflammatory arthritis. The TCR repertoire of the virus-specific T cells in the synovial fluid was analyzed using a panel of TCR beta variable region-specific monoclonal antibodies. Where T cells expressing a particular Vbeta chain dominated the response to a viral epitope, the sequences of these Vbeta chains were derived from sorted populations of antigen-specific T cells by reverse transcription-polymerase chain reaction. RESULTS: CD8+ T cells specific for Epstein-Barr virus, cytomegalovirus, and influenza virus were enriched in synovial fluid compared with
In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β cell-reactive CD8+ T cells that are detectable in the circulation, and their relationship to β cell function, are not known. Here, we tracked multiple, circulating β cell-reactive CD8+ T cell subsets and measured β cell function longitudinally for 2 years, starting immediately after diagnosis of type 1 diabetes. We found that change in β cell-specific effector memory CD8+ T cells expressing CD57 was positively correlated with C-peptide change in subjects below 12 years of age. Autoreactive CD57+ effector memory CD8+ T cells bore the signature of enhanced effector function (higher expression of granzyme B, killer-specific protein of 37 kDa, and CD16, and reduced expression of CD28) compared with their CD57- counterparts, and network association modeling ...
These are some of the tests used to measure memory T-cell responses. While the presence of memory T-cells specific for a particular infection (e.g. CMV) ...
Whether memory T lymphocytes are derived directly from effector T cells or via a separately controlled pathway has long been debated. Here we present evidence that, after adoptive transfer, a large fraction of in vitro-derived effector CD4+ T cells have the potential to become memory T cells and that this transition can occur without further division. This data supports a linear pathway from effector to memory cells and suggests that most properties of memory cells are predetermined during effector generation. We suggest, therefore, that evaluation of vaccine efficacy in the induction of memory CD4+ T cells should focus on the effector stage.
Immunosenescence is the age-associated dysregulation of the immune system, of high clinical relevance, as it contributes to multiple age-related comorbidities, including malignancies, infectious diseases, autoimmune diseases, and degenerative diseases. T cells are important components of the immune system. Age-associated T-cell dysfunction is important for the development of immunosenescence. T-cell senescence is different from T-cell exhaustion, a hyporesponsiveness associated with chronic infections and cancer. Exhausted T cells are derived from activated T cells that progressively lose function because of persistent antigen stimulation, whereas senescence is cell cycle arrest due to aging. However, emerging evidence indicates that T-cell senescence shares several key features with exhaustion. The upregulation of multiple co-inhibitory receptors is not only a hallmark, but also an important mechanism involved in the development of T-cell exhaustion. Consistently, certain co-inhibitory ...
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Priming and stimulation of hepatitis C virus-specific CD4+ and CD8+ T cells against HCV antigens NS4, NS5a or NS5b from HCV-naive individuals: implications for prophylactic vaccine. Wen Li; Deepa K. Krishnadas; Rakesh Kumar; D. Lorne J. Tyrrell; Babita Agrawal // International Immunology;Jan2008, Vol. 20 Issue 1, p89 Hepatitis C virus (HCV) is a devastating human pathogen, yet there is no vaccine available for this virus. From studies with acute or chronic HCV-infected humans and chimpanzees, T-cell responses against HCV-derived conserved non-structural antigens have been correlated with viral clearance. In... ...
The invention of MHC‐tetramer technology to label antigen‐specific T cells has lead to a greatly enhanced understanding of T lymphocyte biology
T cells are crucial mediators of tissue rejection and long-lived immune protection. While HLA class I-restricted CD8-positive T cells are the primary effectors of tissue destruction, CD4-positive T cells support their expansion and memory formation. The identification of T cell target antigens is a prerequisite for the rational development of specific tumor immunotherapies. T cells recognize peptides bound to and presented by HLA molecules on the surfaces of target cells. The peptides are processed from proteins derived from any subcellular compartment. In this way, T cells sense differences between tumor and normal cells. Their sensitivity is exceptional in several aspects: On the one hand, even changes at single amino acid positions can be detected by T cells; on the other hand, the presence of very few peptide-HLA-complexes on target cell surfaces is sufficient for effective T cell recognition. Since 1991 a variety of T cell-recognized tumor-associated antigens has been published. A current ...
IL-10 is generally considered an immune suppressive cytokine and is often cited as one of the molecules responsible for the immune-suppressive environment in tumors. In contrast to this widely held believe, and confirming earlier studies (11-13), we show here that IL-10 induces potent antitumor responses. This antitumor activity required the presence of CD8+ T cells and IL-10 increased the cytotoxic activity of these cells. We show here, for the first time, that in vivo treatment with IL-10 directly induces specific activation and expansion of tumor-resident CD8+ T cells. In human tumors, the number and the activity of intratumoral CD8+ T cells correlates with an improved prognosis for patients with cancer (25). High frequency of tumor-specific T cells in the blood, as can be achieved with cancer vaccines, does not necessarily correlate with improved prognosis (26, 27). Restricted migration of T cells into the tumor can explain why vaccine induced increases in tumor-specific T cells have not ...
While a high frequency of Th1 cells in tumors is associated with improved cancer prognosis, this benefit has been attributed mainly to support of cytotoxic activity of CD8+ T cells. By attempting to potentiate antibody-driven immunity, we found a remarkable synergy between CD4+ T cells and tumor-binding antibodies. This surprising synergy was mediated by a small subset of tumor-infiltrating CD4+ T cells that express the high-affinity Fcγ receptor for IgG (FcγRI) in both mouse and human patients. These cells efficiently lyse tumor cells coated with antibodies through concomitant crosslinking of their T cell receptor (TCR) and FcγRI. By expressing FcγRI and its signaling chain in conventional CD4+ T cells, we successfully employed this mechanism to treat established solid cancers. Overall, this discovery sheds new light on the biology of this T cell subset, their function during tumor immunity, and the means to utilize their unique killing signals in immunotherapy.. ...
While a high frequency of Th1 cells in tumors is associated with improved cancer prognosis, this benefit has been attributed mainly to support of cytotoxic activity of CD8+ T cells. By attempting to potentiate antibody-driven immunity, we found a remarkable synergy between CD4+ T cells and tumor-binding antibodies. This surprising synergy was mediated by a small subset of tumor-infiltrating CD4+ T cells that express the high-affinity Fcγ receptor for IgG (FcγRI) in both mouse and human patients. These cells efficiently lyse tumor cells coated with antibodies through concomitant crosslinking of their T cell receptor (TCR) and FcγRI. By expressing FcγRI and its signaling chain in conventional CD4+ T cells, we successfully employed this mechanism to treat established solid cancers. Overall, this discovery sheds new light on the biology of this T cell subset, their function during tumor immunity, and the means to utilize their unique killing signals in immunotherapy.. ...
easYmer HLA-B*46:01 MHC Tetramers Kit can be used to generate monomers with your choice of peptide and to analyze T-cells by flow cytometry.
Memory T cells exhibit greater effector function than naïve T cells. (a) Fluorescence-activated cell sorting analysis of CD4+ subpopulations. Resting CD4+ lymp
Cytotoxic T cell response and thymic hormonal dysfunction in graft-vs-host mice.: As an approach to dissect complex mechanisms that lead to graft-vs-host (GvH)-
Multicytokine production of CD4+ and CD8+ effectors in the peripheral blood (PBMC) or infiltrating the tumor (TIL) of a patient with renal cell carcinoma. T cells producing IL-10 are highlighted in black on IFN-γ+ and/or TNF-α+ effectors (Polychromatic flow cytometry, Attig et al, Cancer Res 2009;69:8412).. ...
The Journal of Immunology Targeting the Effector Site with IFN- -Inducing TLR Ligands Reactivates Tumor-Resident CD8 T Cell Responses to Eradicate Established Solid Tumors 1 Andrew J. Currie, 2,3 * Robbert
IMMUNERKENNUNG (IMMUNOLOGIE); T-LYMPHOZYTEN (BLUTZELLEN); TIERISCHE MODELLE IN DER MEDIZIN; CHRONISCHE INFEKTIONSKRANKHEITEN (PATHOLOGIE); IMMUNORECOGNITION (IMMUNOLOGY); T LYMPHOCYTES (BLOOD CELLS); ANIMAL MODELS IN MEDICINE; CHRONIC INFECTIOUS DISEASES (PATHOLOGY ...
Figure 5.2-1 illustrates the division of the project into expansion phases, starting with a conventional workshop, and six phases numbered 1A through 1F (you can click drawings for larger versions). Six is an arbitrary number of divisions for what is really a continuous expansion. We chose that number as a reasonable compromise between number of phases to analyze and complexity of the additions in each step. The diagram is a partial functional flow type. It illustrates the time sequence, but only shows some of the inputs and outputs. Functional diagrams show what activities need to be done, but do not pre-determine how. Selecting how to do the tasks is a later design step. Conventional shop equipment and new parts and materials are inputs from outside the project. For simplicity we only show operating the final Phase 1F after building it, but each of the earlier phases will also have production operations. Producing useful outputs is, after all, the main goal of the project.. The expansion ...
The Obama Economy has reached a new low. There have been plenty of economic lows over the past fews years, all generated by the catastrophic policies of President Obama and his Democrat wingmen in Congress: the massive expansion of government,...
The Obama Economy has reached a new low. There have been plenty of economic lows over the past fews years, all generated by the catastrophic policies of President Obama and his Democrat wingmen in Congress: the massive expansion of government,...
This paper develops a simple model, which shows how economic fluctuations can stimulate growth. It is shown that firms tend to invest more in productivity growth during recessions, since the opportunity cost (in terms of forgone profits) of investing capital or labour resources in technological (or managerial) improvements is lower during recessions. It is then established that the average growth rate of the economy increases with the amplitude of the fluctuations and also with their frequency, provided that the initial average duration of recession phases is sufficiently low compared with that of the expansion phases. Finally, the main results of the paper are shown to be consistent with the empirical evidence recently produced by Davis-Haltiwanger (1990) or Blanchard-Diamond (1990) concerning the cyclical behaviour of job re-allocation.
(This abstract was borrowed from another version of this item.)
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Breaking News. A science team have released preliminary news that they can now very easily replicate proof of Cold Fusion / LENR with easy to get material.
We have previously shown that CD4+ T cells are required to optimally expand viral-specific memory CD8+ CTL responses using a human dendritic cell-T cell-based coculture system. OX40 (CD134), a 50-kDa transmembrane protein of the TNFR family, is expressed primarily on activated CD4+ T cells. In murine models, the OX40/OX40L pathway has been shown to play a critical costimulatory role in dendritic cell/T cell interactions that may be important in promoting long-lived CD4+ T cells, which subsequently can help CD8+ T cell responses. The current study examined whether OX40 ligation on ex vivo CD4+ T cells can enhance their ability to help virus-specific CTL responses in HIV-1-infected and -uninfected individuals. OX40 ligation of CD4+ T cells by human OX40L-IgG1 enhanced the ex vivo expansion of HIV-1-specific and EBV-specific CTL from HIV-1-infected and -uninfected individuals, respectively. The mechanism whereby OX40 ligation enhanced help of CTL was independent of the induction of cytokines such ...
TY - JOUR. T1 - Polychromatic flow cytometry analysis of CD34+ hematopoietic stem cells in cryopreserved early preterm human cord blood samples. AU - D'Alessio, F.. AU - Mirabelli, P.. AU - Gorrese, M.. AU - Scalia, G.. AU - Gemei, M.. AU - Mariotti, E.. AU - Di Noto, R.. AU - Martinelli, P.. AU - Fortunato, G.. AU - Paladini, D.. AU - Del Vecchio, L.. PY - 2011/1. Y1 - 2011/1. N2 - During the last decades, extended characterizations were performed of human full-term cord blood (hTCB) cells, but little information is available on human early preterm cord blood (hEPCB) hematopoietic stem cells (HSCs). In our study, we analyzed by flow cytometry 19 hEPCB and 17 hTCB samples. First, we observed that the percentage of CD34 PosCD45 Dim cells was higher in hEPCB compared with hTCB and that it decreased during 16th-20th week of pregnancy. Within the CD34 PosCD45 Dim population, we examined the expression of CD29, CD31, CD38, CD90, CD117, CD133, CD135, CD200, CD243, and CD338. We found that CD135 ...
Looking for online definition of T cytotoxic cell in the Medical Dictionary? T cytotoxic cell explanation free. What is T cytotoxic cell? Meaning of T cytotoxic cell medical term. What does T cytotoxic cell mean?
Cytomegalovirus vectors are promising delivery vehicles for vaccine strategies that aim to elicit effector CD8+ T cells. To determine how the route of immunization affects CD8+ T cell responses in the lungs of mice vaccinated with a murine cytomegalovirus vector expressing the respiratory syncytial virus matrix (M) protein, we infected CB6F1 mice via the intranasal or intraperitoneal route and evaluated the M-specific CD8+ T cell response at early and late time points. We found that intranasal vaccination generated robust and durable tissue-resident effector and effector memory CD8+ T cell populations that were undetectable after intraperitoneal vaccination. The generation of these antigen-experienced cells by intranasal vaccination resulted in earlier T cell responses, interferon gamma secretion, and viral clearance after respiratory syncytial virus challenge. Collectively, these findings validate a novel approach to vaccination that emphasizes the route of delivery as a key determinant of ...
L. monocytogenes is a gram-positive facultative intracellular bacterium which has been used for decades as a model for the study of cell-mediated immunity (6, 26, 27). Long-term resistance to infection by this microorganism resides primarily in the MHC class I-restricted CD8+ T cells that are induced following primary infection (3, 17). These cells act by directly lysing antigen-expressing target cells, as well as through the action of the cytokines gamma interferon and tumor necrosis factor alpha (18). We and other investigators have been exploring the use of recombinant forms of L. monocytogenes as a vehicle for the delivery of foreign antigens into the MHC class I pathway of antigen presentation (13, 15, 22, 32, 33, 40).. This strategy for vaccine development suffers, however, from the known pathogenicity of the organism, which is the cause of listeriosis, a food-borne disease characterized by meningitis, septicemia, abortion, and often a high rate of mortality. We therefore attempted to ...
Recent studies in the SIV-macaque model of HIV infection suggest that Nef-specific CD8+ T-cell responses may mediate highly effective immune control of viraemia. In HIV infection Nef recognition dominates in acute infection, but in large cohort studies of chronically infected subjects, breadth of T cell responses to Nef has not been correlated with significant viraemic control. Improved disease outcomes have instead been associated with targeting Gag and, in some cases, Pol. However analyses of the breadth of Nef-specific T cell responses have been confounded by the extreme immunogenicity and multiple epitope overlap within the central regions of Nef, making discrimination of distinct responses impossible via IFN-gamma ELISPOT assays. Thus an alternative approach to assess Nef as an immune target is needed. Here, we show in a cohort of |700 individuals with chronic C-clade infection that |50% of HLA-B-selected polymorphisms within Nef are associated with a predicted fitness cost to the virus, and that
Previous reports point to the potential advantage of initiating treatment very early, before seroconversion, to preserve or enhance HIV-specific T cell responses. It has been shown that some individuals who were treated early were able to control HIV replication, at least transiently, after HAART was interrupted. This was thought to be related to the earliness of treatment, because such control is uncommon when HAART is stopped during chronic infection. It has been suggested that this virological control could be related to a greater HIV-specific T cell immune response. In our study, the time when the therapy was initiated did not influence the evolution of HIV-specific CD4+ or CD8+ T cell responses, as indicated by the similar changes of these responses in groups of acute and early subjects. Previous data suggested the existence of very high proliferation indices when treatment was initiated in acute infection, before seroconversion. However, in our study, changes in HIV-specific CD4+ T cell ...
Upon activation, naive CD8 T cells undergo a program of proliferation and differentiation that results in the acquisition of effector functions. Optimal T cell activation requires the integration of multiple signals including cross-linking of the T cell receptor (signal 1), co-stimulation (signal 2) and soluble factors such as cytokines (signal 3). Once a CD8 T cell has received these three signals they differentiate into an effector cell, which are able to control infection by directly killing the infected cell. Once the infection is cleared, these effector cells contract by controlled cell death and a long-lived population of memory cells remain. These potent memory cells are the defining feature of adaptive immunity as they offer protection for the life of the host due to their unique capabilities to survive in the absence of antigen and respond rapidly to secondary challenge. Therefore, effective CD8 T cell memory is the goal of cell-mediated vaccination strategies. While it is well ...
Co-Author, The Evidence of Things Not Seen: Non-Matches as Evidence of Innocence, 98 Iowa L. Rev. 577 (2013). Co-Author, Toll-like receptor 7 is required for effective adaptive immune responses that prevent persistent virus infection, Cell Host Microbe., 2012 Jun.. Angelosanto JM, Blackburn SD, Crawford A, Wherry EJ, Progressive loss of memory T cell potential and commitment to exhaustion during chronic viral infection. J Virol., 2012 Aug.. Crawford A, Angelosanto JM, Nadwodny KL, Blackburn SD, Wherry EJ, A role for the chemokine RANTES in regulating CD8 T cell responses during chronic viral infection. PLoS Pathog., 2011 Jul.. Blackburn SD, et al., Tissue-specific differences in PD-1 and PD-L1 expression during chronic viral infection: implications for CD8 T-cell exhaustion. J Virol., 2010 Feb.. Shin H, Blackburn SD, et al., A role for the transcriptional repressor Blimp-1 in CD8(+) T cell exhaustion during chronic viral infection. Immunity, 2009 Aug.. Blackburn SD, et al. Co-regulation of CD8 T ...
Targeted molecular imaging with hyaluronic acid (HA) has been highlighted in the diagnosis and treatment of CD44-overexpressing cancer. CD44, a receptor for HA, is closely related to the growth of cancer including proliferation, metastasis, invasion, and angiogenesis. For the efficient detection of CD44, we fabricated a few kinds of HA-modified MnFe2O4 nanocrystals (MNCs) to serve as specific magnetic resonance (MR) contrast agents (HA-MRCAs) and compared physicochemical properties, biocompatibility, and the CD44 targeting efficiency. Hydrophobic MNCs were efficiently phase-transferred using aminated polysorbate 80 (P80) synthesized by introducing spermine molecules on the hydroxyl groups of P80. Subsequently, a few kinds of HA-MRCAs were fabricated, conjugating different ratios of HA on the equal amount of phase-transferred MNCs. The optimized conjugation ratio of HA against magnetic content was identified to exhibit not only effective CD44 finding ability but also high cell viability through in vitro
While a significant proportion of HIV-2-infected individuals are asymptomatic and maintain undetectable viral loads (controllers), 15% to 20% progress to AIDS and are predicted by detectable viremia. Identifying immune correlates that distinguish these 2 groups should provide insights into how a potentially pathogenic retrovirus can be naturally controlled. We performed a detailed study of HIV-2-specific cellular responses in a unique community cohort in Guinea-Bissau followed for over 2 decades. T-cell responses were compared between controllers (n = 33) and viremic subjects (n = 27) using overlapping peptides, major histocompatibility complex class I tetramers, and multiparameter flow cytometry. HIV-2 viral control was significantly associated with a high-magnitude, polyfunctional Gag-specific CD8(+) T-cell response but not with greater perforin upregulation. This potentially protective HIV-2-specific response is surprisingly narrow. HIV-2 Gag-specific CD8(+) T cells are at an earlier stage of ...
To evaluate the impact of immunodominance on CD8 T-cell properties, we compared the functional properties of dominant and subdominant populations in the response to lymphocytic choriomeningitis virus (LCMV). To improve functional discrimination, in addition to the usual tests of phenotype and function, we used a sensitive technique that allows the screening of all CD8 effector genes simultaneously in single cells. Surprisingly, these methods failed to reveal a major impact of clonal dominance in CD8 properties throughout the response. Aiming to increase clonal dominance, we examined high-frequency transferred P14 T-cell receptor transgenic (TCR Tg) cells. Under these conditions LCMV is cleared faster, and accordingly we found an accelerated response. However, when Tg and endogenous cells were studied in the same mice, where they should be subjected to the same antigen load, they showed overlapping properties, and the presence of P14 cells did not modify endogenous responses to other LCMV epitopes or a
The function of CD8 cells in the human body is to kill infected target cells, such as HIV infected cells. Recent data suggest that intravenous administration of HIV-specific CD8 cells is safe, augments host immunity, and mediates a dramatic reduction in circulating HIV-infected CD4 cells. However, the observed antiviral effects are transient, and HIV infected CD4 cells re-emerge as the number of self CD8 cells declines. Augmenting CD8 cell response to HIV by immunotherapy with CD8 cells may be a useful addition to drug therapy if the infused CD8 cells can survive long-term in vivo. Administration of interleukin-2 (also known as aldesleukin or IL-2), a naturally occurring cytokine, has been proposed as a way to maintain the number of CD8 cells. This study will evaluate the safety and efficacy of immunotherapy with HIV-specific CD8 cells in HIV infected patients. Additionally, this study will determine if aldesleukin injections improve the persistence of self CD8 transplants and the duration of ...
The function of CD8 cells in the human body is to kill infected target cells, such as HIV infected cells. Recent data suggest that intravenous administration of HIV-specific CD8 cells is safe, augments host immunity, and mediates a dramatic reduction in circulating HIV-infected CD4 cells. However, the observed antiviral effects are transient, and HIV infected CD4 cells re-emerge as the number of self CD8 cells declines. Augmenting CD8 cell response to HIV by immunotherapy with CD8 cells may be a useful addition to drug therapy if the infused CD8 cells can survive long-term in vivo. Administration of interleukin-2 (also known as aldesleukin or IL-2), a naturally occurring cytokine, has been proposed as a way to maintain the number of CD8 cells. This study will evaluate the safety and efficacy of immunotherapy with HIV-specific CD8 cells in HIV infected patients. Additionally, this study will determine if aldesleukin injections improve the persistence of self CD8 transplants and the duration of ...
TCR affinity associated with functional differences between dominant and subdominant SIV epitope-specific CD8+ T cells in Mamu-A*01+ rhesus monkeys.
Time: 12:30-1:30 p.m.. Abstract: Through flow cytometry analysis, cell sorting and in vitro techniques, AgonOx has developed a workflow for detecting, isolating and expanding endogenous tumor antigen-specific CD8 T cells from individuals own tumor tissue (Duhen, et al, Nature Communications, volume 9, Article number: 2724 (2018)). The highly enriched tumor-reactive T cells are grown in vitro with a method optimized to achieve large cellular expansion and to maintain a broad repertoire of tumor-reactive T cell clones. The expanded T cell product typically retains much of its original T cell clonal diversity and preserves or reinvigorates its tumor-lytic potential. This platform yields a uniquely personalized subject-derived product for individuals from a wide variety of tumor types. This tumor-specific T cell product is specific/personalized for each subject and has clinical research applications in the immune oncology field. ...
The major focus of my lab is to investigate the mechanisms that control protective immunity to influenza and other respiratory virus infections. These pathogens are a major cause of human mortality every year. Cytotoxic T cells (CTL) play an important role in viral clearance and can provide short-term heterosubtypic immunity, indicating that they could be an effective target for vaccination. Unfortunately, cellular immunity to viral infections lasts only a few months even when large self-renewing populations of virus-specific memory CD8 T cells have been established. An important goal of my lab is to determine why protective cellular immunity declines so rapidly and why circulating memory T cells become ineffective at accelerating viral clearance during secondary challenge. Better understanding of the mechanisms that regulate T cell responses in vivo are likely to lead to more effective methods of vaccination against viruses and other pathogens that invade the respiratory tract. Transgenic mice, ...
Sigma-Aldrich offers abstracts and full-text articles by [Iulia Popescu, Matthew R Pipeling, Pali D Shah, Jonathan B Orens, John F McDyer].
In the absence of foreign antigen, peripheral naive T cells continuously recirculate between different lymphoid organs, in which they interact frequently and shortly with self. We and others have shown that such interactions are required for the long-term survival of naïve T cells. In addition, these TCR/MHC interactions and the resulting associated signaling increase quantitatively T-cell responsiveness towards foreign antigens and influence their function and/or differentiation into effector or memory cells in response to stimulation. Our project is based on our recent data showing that peripheral ab and gd T cells can be subdivided into various subsets according to Ly-6C expression. Interestingly, in CD4 ab T cells, Ly-6C expression inversely correlates with the ability of these cells to interact with self, defining Ly-6C as a new sensor of T cell self-reactivity. In parallel, we are exploring the regulation of T-cell self-reactivity in the context of cancer. Indeed, T cells specific for ...
CD4+ T cells within lymphoid tissue throughout the body represent the major site of HIV infection and the long-term HIV reservoir that prevents the development of an HIV cure and hampers vaccine development strategies. CD8+ T cell activity is thought to be responsible for controlling HIV replication, but our preliminary data indicates tht this activity is dysfunctional within lymphoid tissue. This proposal will define the function and dysfunction of lymphoid tissue CD8+ T cells in order to define strategies for eliminating HIV infection.. ...
TY - JOUR. T1 - CD4 T cell-mediated protection from lethal influenza. T2 - Perform and antibody-mediated mechanisms give a one-two punch. AU - Brown, Deborah M.. AU - Dilzer, Allison M.. AU - Meents, Dana L.. AU - Swain, Susan L.. PY - 2006/9/1. Y1 - 2006/9/1. N2 - The mechanisms whereby CD4 T cells contribute to the protective response against lethal influenza infection remain poorly characterized. To define the role of CD4 cells in protection against a highly pathogenic strain of influenza, virus-specific TCR transgenic CD4 effectors were generated in vitro and transferred into mice given lethal influenza infection. Primed CD4 effectors conferred protection against lethal infection over a broad range of viral dose. The protection mediated by CD4 effectors did not require IFN-γ or host T cells, but did result in increased anti-influenza Ab titers compared with untreated controls. Further studies indicated that CD4-mediated protection at high doses of influenza required B cells, and that ...
NK cells are the first line of defense against infected and transformed cells. Defective NK cell activity was shown to increase susceptibility for viral infections and reduce tumor immune-surveillance. With age, the incidence of infectious diseases and malignancy rises dramatically, suggesting that impaired NK cell function might contribute to disease in these individuals. We found an increased frequency of NK cells with high expression of the inhibitory killer cell lectin-like receptor G1 (KLRG1) in individuals |70 y. The role of KLRG1 in ageing is not known, and the mechanism of KLRG1-induced inhibition of NK cell function is not fully understood. We report that NK cells with high KLRG1 expression spontaneously activate the metabolic sensor AMP-activated protein kinase (AMPK) and that activation of AMPK negatively regulates NK cell function. Pre-existing AMPK activity is further amplified by ligation of KLRG1 in these cells, which leads to internalization of the receptor and allows interaction with
Gehring, A.J., Ho, Z.Z., Tan, A.T., Bertoletti, A., Aung, M.O., Lim, S.G., Lee, K.H., Tan, K.C., Lim, S.G. (2009). Profile of Tumor Antigen-Specific CD8 T Cells in Patients With Hepatitis B Virus-Related Hepatocellular Carcinoma. Gastroenterology 137 (2) : 682-690. [email protected] Repository. https://doi.org/10.1053/j.gastro.2009.04. ...
A successful T cell immune response has two major products: effector T cells which directly or indirectly remove the antigens, and memory T cells, which allow a faster and more efficient recall response when challenged by related antigens. An important issue is whether costimulatory molecules on the antigen-presenting cells are involved in determining whether T cells will differentiate into effector or memory cells after antigenic stimulation. To address this issue, we have produced mice with targeted mutations of either the heat-stable antigen (HSA), or both HSA and CD28. We show that CD28/B7 and HSA provide two alternative costimulatory pathways for induction of immunological memory to influenza virus. Furthermore, our results revealed that B7 is essential for the generation of effector T cells from either naive or memory T cells, while HSA is not necessary for the generation of effector T cells. Our results demonstrate that the induction of memory T cells and effector T cells can utilize ...
TY - JOUR. T1 - Bacterial and Host Factors Involved in the Major Histocompatibility Complex Class Ib-Restricted Presentation of Salmonella Hsp 60. T2 - Novel Pathway. AU - Lo, Wei Feng. AU - Dunn, Cory D.. AU - Ong, Helena. AU - Metcalf, Eleanor S.. AU - Soloski, Mark J.. PY - 2004/5/1. Y1 - 2004/5/1. N2 - Previously, a peptide epitope derived from the Hsp 60 molecule of Salmonella that is presented by the major histocompatibility complex (MHC) class Ib molecule Qa-1 to CD8+ cytotoxic T cells (CTLs) was described. In the present study we investigated the Salmonella-induced processing and presentation pathway for generating this Qa-1-restricted epitope. Live bacteria and, to a lesser extent, opsonized heat-killed bacteria are able to sensitize target cells for lysis by Salmonella-specific CTL. In contrast, heat-killed bacteria cannot sensitize target cells. Presentation of the Hsp 60 epitope appears independent of bacterial internalization, because cytochalasin D does not affect presentation. ...
TY - JOUR. T1 - Association between immune recovery uveitis and a diverse intraocular cytomegalovirus-specific cytotoxic T cell response. AU - Mutimer, Helen P.. AU - Akatsuka, Yoshiki. AU - Manley, Thomas. AU - Chuang, Elaine L.. AU - Boeckh, Michael. AU - Harrington, Robert. AU - Jones, Thomas. AU - Riddell, Stanley R.. PY - 2002/9/1. Y1 - 2002/9/1. N2 - Cytomegalovirus (CMV) causes serious infection in individuals with deficient T cell immunity. In acquired immunodeficiency syndrome, the retina is a major site of progressive infection, despite the availability of therapy that targets CMV. The administration of highly active antiretroviral therapy to suppress human immunodeficiency virus frequently results in resolution of CMV retinitis, but this may be complicated by ocular inflammation termed "immune recovery uveitis" (IRU). To provide insight into the pathogenesis of IRU, the phenotype and specificity of intraocular T cells in a single patient were analyzed. The T cell infiltrate consisted ...

CD8-positive lymphocytes in graft-versus-host disease of humanized NOD.Cg-Prkdc<sup>scid</sup> Il2rg<sup>tm1Wjl...CD8-positive lymphocytes in graft-versus-host disease of humanized NOD.Cg-Prkdc<sup>scid</sup> Il2rg<sup>tm1Wjl...

CD8-positive lymphocytes in graft-versus-host disease of humanized NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. / Laing, S. T.; ... CD8-positive lymphocytes in graft-versus-host disease of humanized NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Journal of ... Laing, S. T., Griffey, S. M., Moreno, M. E., & Stoddart, C. A. (2015). CD8-positive lymphocytes in graft-versus-host disease of ... Laing, S. T. ; Griffey, Stephen M ; Moreno, M. E. ; Stoddart, C. A. / CD8-positive lymphocytes in graft-versus-host disease of ...
more infohttps://ucdavis.pure.elsevier.com/en/publications/cd8-positive-lymphocytes-in-graft-versus-host-disease-of-humanize

Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T...Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T...

In order to determine the fine structural differences and labeling by immunoferritin particles of CD4-positive (CD4+) and CD8 ... Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T- ... and CD8 positive (CD8+) cells at the ultrastructural level, short term cultured lymphocytes from eight healthy donors ... Sera of eight donors were all positive on the particle agglutination (PA) test, but only of the four of the eight were positive ...
more infohttp://www.alliedacademies.org/abstract/immunoelectronmicroscopic-study-of-cd4-and-cd8-positive-lymphocytes-from-healthy-donors-seropositive-for-human-tlymphotropic-virus-723.html

Cd8-positive t-lymphocytes | definition of Cd8-positive t-lymphocytes by Medical dictionaryCd8-positive t-lymphocytes | definition of Cd8-positive t-lymphocytes by Medical dictionary

What is Cd8-positive t-lymphocytes? Meaning of Cd8-positive t-lymphocytes medical term. What does Cd8-positive t-lymphocytes ... Looking for online definition of Cd8-positive t-lymphocytes in the Medical Dictionary? Cd8-positive t-lymphocytes explanation ... Cd8-positive t-lymphocytes , definition of Cd8-positive t-lymphocytes by Medical dictionary https://medical-dictionary. ... redirected from Cd8-positive t-lymphocytes). Also found in: Dictionary, Thesaurus, Encyclopedia. cytotoxic T cell. n.. See ...
more infohttp://medical-dictionary.thefreedictionary.com/Cd8-positive+t-lymphocytes

CD4-Positive and CD8-Positive Cytotoxic T Lymphocytes Contribute to Human Papillomavirus Type 16 E6 and E7 Responses | Clinical...CD4-Positive and CD8-Positive Cytotoxic T Lymphocytes Contribute to Human Papillomavirus Type 16 E6 and E7 Responses | Clinical...

CD4-Positive and CD8-Positive Cytotoxic T Lymphocytes Contribute to Human Papillomavirus Type 16 E6 and E7 Responses. Mayumi ... CD4-Positive and CD8-Positive Cytotoxic T Lymphocytes Contribute to Human Papillomavirus Type 16 E6 and E7 Responses ... CD4-Positive and CD8-Positive Cytotoxic T Lymphocytes Contribute to Human Papillomavirus Type 16 E6 and E7 Responses ... CD4-Positive and CD8-Positive Cytotoxic T Lymphocytes Contribute to Human Papillomavirus Type 16 E6 and E7 Responses ...
more infohttps://cvi.asm.org/content/6/4/494

Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T...Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T...

title = "Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T- ... T1 - Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T- ... Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T- ... Immunoelectron-microscopic study of CD4- and CD8- positive lymphocytes from healthy donors seropositive for human T- ...
more infohttps://okayama.pure.elsevier.com/en/publications/immunoelectron-microscopic-study-of-cd4-and-cd8-positive-lymphocy

Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in...Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in...

PD-L1−/CD8Low, 22.7%; PD-L1+/CD8Low, 2.3%; PD-L1−/CD8High, 52.3%. PD-L1+/CD8High type accounted for majority of EBV+ and MSI- ... Clinicopathologic implications of immune classification by PD-L1 expression and CD8-positive tumor-infiltrating lymphocytes in ... PD-L1−/CD8High showed the best overall survival (OS) and PD-L1−/CD8Low the worst (P , 0.001). PD-L1 expression alone was not ... We co-assessed PD-L1 expression and CD8+ tumor-infiltrating lymphocytes in gastric cancer (GC), and categorized into 4 ...
more infohttp://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=15465

Publications | AIDS Clinical Trials GroupPublications | AIDS Clinical Trials Group

CD8-Positive T-Lymphocytes. Pereyra F, Jia X, McLaren PJ, et al. "The major genetic determinants of HIV-1 control affect HLA ...
more infohttps://actgnetwork.org/pubmed_publications?s=keyword&o=asc&f%5Bauthor%5D=22

Tumor Pre-Analytics in Molecular Pathology: Impact on Protein Expression and Analysis | SpringerLinkTumor Pre-Analytics in Molecular Pathology: Impact on Protein Expression and Analysis | SpringerLink

... in a significant increase of CD8-positive lymphocytes within the tumor microenvironment but a decrease in FOXP3-positive T cell ... No changes were reported for circulating CD8-positive lymphocytes. Metabolomic profiling of pre- and postanesthesia plasma ... while viability and apoptosis of circulating CD4-positive lymphocytes were significantly affected by propofol administration [8 ... Lower levels of oxidative DNA damage and apoptosis in lymphocytes from patients undergoing surgery with propofol anesthesia. ...
more infohttps://link.springer.com/article/10.1007%2Fs40139-018-0179-5

Effectiveness of Adding Interleukin-2 to Anti-HIV Drugs in Patients Recently Infected With HIV - Full Text View -...Effectiveness of Adding Interleukin-2 to Anti-HIV Drugs in Patients Recently Infected With HIV - Full Text View -...

CD4-Positive T-Lymphocytes. CD8-Positive T-Lymphocytes. Biological Markers. Lamivudine. Reverse Transcriptase Inhibitors. Anti- ... cytotoxic T cell lymphocyte function and CD4 T helper function correlates with the patterns of cellular immune antiviral ... a cohort of HIV negative individuals that tested with the Options Project to use as a comparison group with the HIV positive ...
more infohttps://clinicaltrials.gov/show/NCT00006441?order=38

The Biology of HIV Transmission - Full Text View - ClinicalTrials.govThe Biology of HIV Transmission - Full Text View - ClinicalTrials.gov

CD8-Positive T-Lymphocytes. Saliva. Blood. Cervix Uteri. Vagina. Acute Infection. Additional relevant MeSH terms: ... or if they have recently become HIV-positive. ...
more infohttps://clinicaltrials.gov/show/NCT00001092?order=113

Pre-operative Mocetinostat (MGCD0103) and Durvalumab (MEDI4736) (PRIMED) for Squamous Cell Carcinoma of the Oral Cavity - Full...Pre-operative Mocetinostat (MGCD0103) and Durvalumab (MEDI4736) (PRIMED) for Squamous Cell Carcinoma of the Oral Cavity - Full...

CD4 and CD8-positive lymphocytes; Serum pro-inflammatory cytokines and chemokines) [ Time Frame: 3 years ]. *Immune effects ... CD4 and CD8-positive lymphocytes; Serum pro-inflammatory cytokines and chemokines) [ Time Frame: 3 years ]. ...
more infohttps://www.clinicaltrials.gov/ct2/show?term=Oral+Cancer&map_cntry=CA&rank=56

The effects of altered exercise distribution on lymphocyte subpopulations.The effects of altered exercise distribution on lymphocyte subpopulations.

... lymphocyte subpopulations and plasma cortisol concentration in peripheral blood were assessed in 19 healthy subjects. The ... The effects of exercise distribution on lymphocyte count, ... CD4-Positive T-Lymphocytes. CD8-Positive T-Lymphocytes. ... The effects of exercise distribution on lymphocyte count, lymphocyte subpopulations and plasma cortisol concentration in ... CD4+ and CD8+ lymphocytes. The S2 variables statistically significant from B were: total lymphocyte count (P , 0.01), CD3+ T- ...
more infohttp://www.biomedsearch.com/nih/effects-altered-exercise-distribution-lymphocyte/8789587.html

Total-Body Irradiation, Fludarabine, and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic CancerTotal-Body Irradiation, Fludarabine, and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer

Cd8-positive T-lymphocytes. A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted ... T-lymphocytes. Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, ... They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes. ... CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the ...
more infohttps://www.bioportfolio.com/resources/trial/122430/Total-Body-Irradiation-Fludarabine-and-Peripheral-Stem-Cell-Transplantation-in-Treating-Patients.html

Interleukin-4 in the treatment of AIDS-related Kaposis sarcoma.Interleukin-4 in the treatment of AIDS-related Kaposi's sarcoma.

CD4 Lymphocyte Count / drug effects. CD8-Positive T-Lymphocytes. Capillary Leak Syndrome / chemically induced. Disease ... Lymphocyte Count / drug effects. Male. Middle Aged. Mouth Neoplasms / etiology, immunology, therapy*. Remission Induction. ... Seventeen had CD4+ lymphocyte counts less than 200/mm3. RESULTS: The most common adverse effects included headache in 78%, ... IL-4 produced minimal anti-tumor effects in AIDS-KS with one partial remission in a patient with CD4 lymphocyte counts over 200 ...
more infohttp://www.biomedsearch.com/nih/Interleukin-4-in-treatment-AIDS/9093711.html

Lichen Planus - The Clinical AdvisorLichen Planus - The Clinical Advisor

Both CD4- and CD8-positive lymphocytes have been implicated. Increased keratinocyte expression of ICAM-4, an adhesion molecule ... It is believed to be an autoimmune disorder involving the activation of T-lymphocytes against basal keratinocytes. ... positive potassium hydroxide test or fungal culture); 3) psoriasis (nail pitting, oil staining, onycholysis, skin involvement). ... may play a role in the interaction between T-lymphocytes and basal keratinocytes. This interaction leads to apoptosis of basal ...
more infohttps://www.clinicaladvisor.com/dermatology/lichen-planus/article/589089/

CiNii 論文 - 
 		
 		
 			
 		 	
 		 		
 		 			Systemic Capillary Leak Syndrome
 		 		
 		 		
 		 	
 		
 	CiNii 論文 - Systemic Capillary Leak Syndrome

Idiopathic capillary leak syndrome: evidence of CD8-positive lymphocytes surrounding damaged endothelial cells CICARDI M. ...
more infohttp://ci.nii.ac.jp/naid/10008034482

Langerhans Cell Histiocytosis Treatment (PDQ®) (Health professionals) | OncoLinkLangerhans Cell Histiocytosis Treatment (PDQ®) (Health professionals) | OncoLink

Mass lesions in connective tissue spaces with CD1a-positive LCH cells and predominantly CD8-positive lymphocytes that cause an ... Mass lesions in the meninges or choroid plexus with CD1a-positive LCH cells and predominantly CD8-positive lymphocytes. ... These lesions contain CD1a-positive LCH cells and CD8-positive lymphocytes and are, therefore, active LCH lesions. ... Predominantly CD8-positive lymphocyte infiltration with neuronal degeneration, microglial activation, and gliosis. ...
more infohttps://www.oncolink.org/healthcare-professionals/nci/pqid-CDR00006005502

Progressive Multifocal Leukoencephalopathy | The New York Academy of SciencesProgressive Multifocal Leukoencephalopathy | The New York Academy of Sciences

Treatment with an anti-CD8 monoclonal antibody lead to transient depletion of CD8-positive lymphocytes. In combination, these ... Interestingly, CD8+ T cell-deficient (i.e., CD8α-/-) mice showed increased virus levels in the brain but not in the spleen, ... Flow cytometric analysis of CNS-derived lymphocytes showed a robust infiltration by MPyV-specific CD8+ T cells, but with ... T Lymphocyte-mediated Cellular Immune Response against JC Virus in PML Patients. Igor J. Koralnik, MD, Beth Israel Deaconess ...
more infohttps://www.nyas.org/events/2013/progressive-multifocal-leukoencephalopathy/

Mistletoe (Viscum album) | Plant Profiler | Sigma-AldrichMistletoe (Viscum album) | Plant Profiler | Sigma-Aldrich

Iscador QuS seems to activate the cytotoxic CD8-positive lymphocytes, important in cancer patients.68Clinical application of ... 10 Lectins can induce apoptosis in lymphocytes (activity: ML-3,ML-2,ML-1), human peripheral blood lymphocytes, human peripheral ... The B chain activates macrophages and release lymphokines from lymphocytes. The contents and proportions of the isoforms in the ... Iscador QuFrF and Iscador Qu Special show immunomodulating qualities in HIV-positive patients, healthy non-smokers and cancer ...
more infohttps://www.sigmaaldrich.com/life-science/nutrition-research/learning-center/plant-profiler/viscum-album.html

TNFRSF4 TNF receptor superfamily member 4 [Homo sapiens (human)] - Gene - NCBITNFRSF4 TNF receptor superfamily member 4 [Homo sapiens (human)] - Gene - NCBI

Title: OX40 expression enhances the prognostic significance of CD8 positive lymphocyte infiltration in colorectal cancer. ... positive regulation of B cell proliferation IBA Inferred from Biological aspect of Ancestor. more info ... positive regulation of B cell proliferation ISS Inferred from Sequence or Structural Similarity. more info ... positive regulation of immunoglobulin secretion IBA Inferred from Biological aspect of Ancestor. more info ...
more infohttps://www.ncbi.nlm.nih.gov/gene/7293

Naturopathic Maine - Breast Cancer DietNaturopathic Maine - Breast Cancer Diet

CD8 positive T lymphocytes may play a key role in the preventive effect against colon carcinogenesis. ... And oral administration of viable LcS significantly recovered CD8 positive lymphocytes to the levels in the control group. In a ... MT1 expression was higher in estrogen receptor positive (ER+) and HER2 positive (HER2+) tumors. Triple negative tumors (TN) ... positive tumors. This study investigated whether an HC diet increases human ER-positive breast cancer progression and modulates ...
more infohttps://sites.google.com/view/naturopathicmaine/maloneys-brain/breast-cancer-diet

Therapeutic Vaccination With Dendritic Cells Loaded With Autologous HIV Type 1-Infected Apoptotic Cells. - NextBio articleTherapeutic Vaccination With Dendritic Cells Loaded With Autologous HIV Type 1-Infected Apoptotic Cells. - NextBio article

CD8-Positive T-Lymphocytes Cell- and Tissue-Based Therapy Dendritic Cells HIV Infections HIV-1 Humans Transplantation, ...
more infohttp://www.nextbio.com/b/search/article.nb?id=26647281

Actinic reticuloid definition | Drugs.comActinic reticuloid definition | Drugs.com

... there is infiltration by atypical CD8-positive T lymphocytes. ...
more infohttps://www.drugs.com/dict/actinic-reticuloid.html

Hantavirus-Driven PD-L1/PD-L2 Upregulation: An Imperfect Viral Immune Evasion Mechanism - PubMedHantavirus-Driven PD-L1/PD-L2 Upregulation: An Imperfect Viral Immune Evasion Mechanism - PubMed

CD8-Positive T-Lymphocytes / immunology *. Actions. * Search in PubMed * Search in MeSH ... Positive controls are given in the lower panel (B7-H2 and B7-H3 from HUVEC, B7-H4 from HEK293 cells transfected with a B7-H4 ... Red samples also tested additionally positive for hantavirus RNA and are therefore acute infections. (D) Levels of sPD-L1 in ... Human brain endothelial cells endeavor to immunoregulate CD8 T cells via PD-1 ligand expression in multiple sclerosis. Pittet ...
more infohttps://pubmed.ncbi.nlm.nih.gov/30559738/?from_term=Raftery+MJ%5Bau%5D&from_pos=4

September 15, 2014 - The ASCO PostSeptember 15, 2014 - The ASCO Post

PD-1 Identifies Patient-Specific CD8-Positive Tumor-Infiltrating Lymphocytes in Melanoma. Adoptive transfer of tumor- ... markers to identify and select patient-specific repertoires of tumor-reactive and mutation-specific CD8-positive lymphocytes, ... infiltrating lymphocytes can mediate regression of metastatic melanoma. However, there are no effective ...
more infohttps://www.ascopost.com/issues/september-15-2014/
  • Moreover, NKG2D and TCR triggering was also observed by peripheral blood derived T lymphocyte- or T cell clone-mediated tumor recognition, both in melanoma and colorectal cancer (CRC) patients. (mendeley.com)
  • The effects of exercise distribution on lymphocyte count, lymphocyte subpopulations and plasma cortisol concentration in peripheral blood were assessed in 19 healthy subjects. (biomedsearch.com)
  • VAP-1-dependent, oligosaccharide-dependent peripheral lymph node (PLN) HEV adhesion under shear was independent of L-selectin, P-selectin glycoprotein ligand 1, and alpha4 integrins, the known lymphocyte receptors involved in the initial recognition of endothelial cells. (nih.gov)
  • PLN HEV adhesion was also critically dependent on peripheral lymph node vascular addressins (PNAds), but lymphocyte L-selectin was absolutely required for PNAd binding. (nih.gov)
  • Tumor cells may overexpress the stress-inducible NKG2D ligands (NKG2DLs: MICA/B, ULBPs) and the NKG2D signaling has been shown to be involved in lymphocyte-mediated anti-tumor activity. (mendeley.com)
  • Interactions between lymphocyte surface receptors and their ligands on vascular endothelial cells regulate the exit of lymphocytes from the circulation. (nih.gov)
  • The overlapping function of L-selectin ligands and VAP-1 in PLN introduces a new control point into the lymphocyte extravasation process. (nih.gov)
  • Pembrolizumab (Keytruda) showed activity in previously treated patients with advanced programmed cell death ligand 1 (PD-L1)-positive endometrial cancer in a cohort of the phase Ib KEYNOTE-028 study. (ascopost.com)
  • Together, our data show that a combination of DNA and MVA immunization induced robust, durable, multifunctional CD4(+) and CD8(+) responses in baboons targeting multiple HIV epitopes that may home to mucosal sites. (curehunter.com)
  • However 2 weeks of overload training followed by 2 weeks of active recovery (baseline) training may induce an increase in the lymphocyte count. (biomedsearch.com)
  • Immunohistochemistry ( PD-L1 , CD8, Foxp3, E-cadherin, and p53), PD-L1 mRNA in situ hybridization (ISH), microsatellite instability (MSI), and EBV ISH were performed in 392 stage II/III GCs treated with curative surgery and fluoropyrimidine-based adjuvant chemotherapy, and two public genome databases were analyzed for validation. (oncotarget.com)
  • This study expands on recently reported microscopical features of GvHD in NSG-hu-BLT mice and suggests a role for CD 8+ T lymphocytes in the progression of the disease. (elsevier.com)
  • Our results suggest that both CD4 and CD8 T lymphocytes contribute to HPV-16 E6- and E7-specific CTL responses although their relative contributions vary from individual to individual. (asm.org)
  • These findings support the close relationship between PD-L1/CD8 status based immune types and EBV + , MSI-H GCs, and their prognostic significance in stage II/III GCs. (oncotarget.com)
  • Recombinant 9 kD granulysin is broadly cytolytic against tumors and microbes, including gram positive and gram negative bacteria, fungi/yeast and parasites. (wikipedia.org)
  • The results indicated that provided the amount of exercise is constant for a given period, then exercise distribution is not a critical variable in the alteration of lymphocyte subpopulations that may occur in response to overload training. (biomedsearch.com)
  • PD-L1 + /CD8 High type accounted for majority of EBV + and MSI-high (MSI-H) GCs (92.0% and 66.7%, respectively), and genome analysis from public datasets demonstrated similar pattern. (oncotarget.com)
  • Binding of an immunomagnetically separated L-selectin- positive subpopulation of PBL to PLNs was also efficiently blocked by mAb 1B2 pretreatment (Fig. 3 C). Therefore, we determined whether L-selectin, although not necessary for lymphocyte binding to VAP-1, can also function as a receptor of VAP-1. (nih.gov)
  • Sera of eight donors were all positive on the particle agglutination (PA) test, but only of the four of the eight were positive on the immunofluorescence (IF) test. (alliedacademies.org)