Removal, via CELL DEATH, of immature lymphocytes that interact with antigens during maturation. For T-lymphocytes this occurs in the thymus and ensures that mature T-lymphocytes are self tolerant. B-lymphocytes may also undergo clonal deletion.
Endogenous superantigens responsible for inducing strong proliferative responses in T-cells in mixed lymphocyte reactions (see LYMPHOCYTE CULTURE TEST, MIXED). They are encoded by mouse mammary tumor viruses that have integrated into the germ line as DNA proviruses (MINOR LYMPHOCYTE STIMULATORY LOCI).
A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus.
A single, unpaired primary lymphoid organ situated in the MEDIASTINUM, extending superiorly into the neck to the lower edge of the THYROID GLAND and inferiorly to the fourth costal cartilage. It is necessary for normal development of immunologic function early in life. By puberty, it begins to involute and much of the tissue is replaced by fat.
Deletion of sequences of nucleic acids from the genetic material of an individual.
Actual loss of portion of a chromosome.
The specific failure of a normally responsive individual to make an immune response to a known antigen. It results from previous contact with the antigen by an immunologically immature individual (fetus or neonate) or by an adult exposed to extreme high-dose or low-dose antigen, or by exposure to radiation, antimetabolites, antilymphocytic serum, etc.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
A group of genetically identical cells all descended from a single common ancestral cell by mitosis in eukaryotes or by binary fission in prokaryotes. Clone cells also include populations of recombinant DNA molecules all carrying the same inserted sequence. (From King & Stansfield, Dictionary of Genetics, 4th ed)
The normal lack of the ability to produce an immunological response to autologous (self) antigens. A breakdown of self tolerance leads to autoimmune diseases. The ability to recognize the difference between self and non-self is the prime function of the immune system.
T-cell receptors composed of CD3-associated alpha and beta polypeptide chains and expressed primarily in CD4+ or CD8+ T-cells. Unlike immunoglobulins, the alpha-beta T-cell receptors recognize antigens only when presented in association with major histocompatibility (MHC) molecules.
An orphan nuclear receptor that is closely related to members of the thyroid-steroid receptor gene family. It was originally identified in NERVE CELLS and may play a role in mediation of NERVE GROWTH FACTOR-induced CELL DIFFERENTIATION. However, several other functions have been attributed to this protein including the positive and negative regulation of APOPTOSIS.
Functional inactivation of T- or B-lymphocytes rendering them incapable of eliciting an immune response to antigen. This occurs through different mechanisms in the two kinds of lymphocytes and can contribute to SELF TOLERANCE.
HEMATOPOIETIC PROGENITOR CELLS that have migrated to the THYMUS where they differentiate into T-LYMPHOCYTES. Thymocytes are classified into maturational stages based on the expression of CELL SURFACE ANTIGENS.
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.
Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.
The grafting of skin in humans or animals from one site to another to replace a lost portion of the body surface skin.
The major group of transplantation antigens in the mouse.
Microbial antigens that have in common an extremely potent activating effect on T-cells that bear a specific variable region. Superantigens cross-link the variable region with class II MHC proteins regardless of the peptide binding in the T-cell receptor's pocket. The result is a transient expansion and subsequent death and anergy of the T-cells with the appropriate variable regions.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.
55-kDa antigens found on HELPER-INDUCER T-LYMPHOCYTES and on a variety of other immune cell types. CD4 antigens are members of the immunoglobulin supergene family and are implicated as associative recognition elements in MAJOR HISTOCOMPATIBILITY COMPLEX class II-restricted immune responses. On T-lymphocytes they define the helper/inducer subset. CD4 antigens also serve as INTERLEUKIN-15 receptors and bind to the HIV receptors, binding directly to the HIV ENVELOPE PROTEIN GP120.
Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.
An organism whose body contains cell populations of different genotypes as a result of the TRANSPLANTATION of donor cells after sufficient ionizing radiation to destroy the mature recipient's cells which would otherwise reject the donor cells.
A sex-specific cell surface antigen produced by the sex-determining gene of the Y chromosome in mammals. It causes syngeneic grafts from males to females to be rejected and interacts with somatic elements of the embryologic undifferentiated gonad to produce testicular organogenesis.
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.
A classification of T-lymphocytes, especially into helper/inducer, suppressor/effector, and cytotoxic subsets, based on structurally or functionally different populations of cells.
Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.
Immunosuppression by reduction of circulating lymphocytes or by T-cell depletion of bone marrow. The former may be accomplished in vivo by thoracic duct drainage or administration of antilymphocyte serum. The latter is performed ex vivo on bone marrow before its transplantation.
The genetic region which contains the loci of genes which determine the structure of the serologically defined (SD) and lymphocyte-defined (LD) TRANSPLANTATION ANTIGENS, genes which control the structure of the IMMUNE RESPONSE-ASSOCIATED ANTIGENS, HUMAN; the IMMUNE RESPONSE GENES which control the ability of an animal to respond immunologically to antigenic stimuli, and genes which determine the structure and/or level of the first four components of complement.
An encapsulated lymphatic organ through which venous blood filters.
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.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Ordered rearrangement of T-cell variable gene regions coding for the beta-chain of antigen receptors.
An individual that contains cell populations derived from different zygotes.
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.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Ratio of T-LYMPHOCYTES that express the CD4 ANTIGEN to those that express the CD8 ANTIGEN. This value is commonly assessed in the diagnosis and staging of diseases affecting the IMMUNE SYSTEM including HIV INFECTIONS.
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.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
An albumin obtained from the white of eggs. It is a member of the serpin superfamily.
Refers to animals in the period of time just after birth.
The type species of BETARETROVIRUS commonly latent in mice. It causes mammary adenocarcinoma in a genetically susceptible strain of mice when the appropriate hormonal influences operate.
Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.
A soluble substance elaborated by antigen- or mitogen-stimulated T-LYMPHOCYTES which induces DNA synthesis in naive lymphocytes.
The process by which antigen is presented to lymphocytes in a form they can recognize. This is performed by antigen presenting cells (APCs). Some antigens require processing before they can be recognized. Antigen processing consists of ingestion and partial digestion of the antigen by the APC, followed by presentation of fragments on the cell surface. (From Rosen et al., Dictionary of Immunology, 1989)
Costimulatory T-LYMPHOCYTE receptors that have specificity for CD80 ANTIGEN and CD86 ANTIGEN. Activation of this receptor results in increased T-cell proliferation, cytokine production and promotion of T-cell survival.
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
Substances that are toxic to the intestinal tract causing vomiting, diarrhea, etc.; most common enterotoxins are produced by bacteria.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Substances that are recognized by the immune system and induce an immune reaction.
Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
The survival of a graft in a host, the factors responsible for the survival and the changes occurring within the graft during growth in the host.
Antibodies produced by a single clone of cells.
Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system.
Receptors present on activated T-LYMPHOCYTES and B-LYMPHOCYTES that are specific for INTERLEUKIN-2 and play an important role in LYMPHOCYTE ACTIVATION. They are heterotrimeric proteins consisting of the INTERLEUKIN-2 RECEPTOR ALPHA SUBUNIT, the INTERLEUKIN-2 RECEPTOR BETA SUBUNIT, and the INTERLEUKIN RECEPTOR COMMON GAMMA-CHAIN.
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.
Immunized T-lymphocytes which can directly destroy appropriate target cells. These cytotoxic lymphocytes may be generated in vitro in mixed lymphocyte cultures (MLC), in vivo during a graft-versus-host (GVH) reaction, or after immunization with an allograft, tumor cell or virally transformed or chemically modified target cell. The lytic phenomenon is sometimes referred to as cell-mediated lympholysis (CML). These CD8-positive cells are distinct from NATURAL KILLER CELLS and NATURAL KILLER T-CELLS. There are two effector phenotypes: TC1 and TC2.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
Progenitor cells from which all blood cells derive.
Any method used for determining the location of and relative distances between genes on a chromosome.
Biochemical identification of mutational changes in a nucleotide sequence.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A specific pair of GROUP G CHROMOSOMES of the human chromosome classification.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
Established cell cultures that have the potential to propagate indefinitely.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
An individual in which both alleles at a given locus are identical.
Condition with a variable constellation of phenotypes due to deletion polymorphisms at chromosome location 22q11. It encompasses several syndromes with overlapping abnormalities including the DIGEORGE SYNDROME, VELOCARDIOFACIAL SYNDROME, and CONOTRUNCAL AMOMALY FACE SYNDROME. In addition, variable developmental problems and schizoid features are also associated with this syndrome. (From BMC Med Genet. 2009 Feb 25;10:16) Not all deletions at 22q11 result in the 22q11deletion syndrome.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
Proteins found in any species of bacterium.
Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.

Cytotoxic T lymphocytes to an unmutated tumor rejection antigen P1A: normal development but restrained effector function in vivo. (1/361)

Unmutated tumor antigens are chosen as primary candidates for tumor vaccine because of their expression on multiple lineages of tumors. A critical issue is whether unmutated tumor antigens are expressed in normal cells, and if so, whether such expression imposes special restrictions on cytotoxic T lymphocyte (CTL) responses. In this study, we use a transgenic approach to study the development and effector function of T cells specific for P1A, a prototypical unmutated tumor antigen. We report here that although P1A is expressed at low levels in normal tissues, including lymphoid tissues, the P1A-specific transgenic T cells develop normally and remain highly responsive to the P1A antigen. The fact that transgenic expression of P1A antigen in the thymus induces T cell clonal deletion demonstrates that normal hematopoietic cells can process and present the P1A antigen and that P1A-specific T cells are susceptible to clonal deletion. By inference, P1A-specific T cells must have escaped clonal deletion due to low expression of P1A in the thymus. Interestingly, despite the fact that an overwhelming majority of T cells in the T cell receptor for antigen (TCR)-transgenic mice are specific for P1A, these mice are no more resistant to a P1A-expressing plasmocytoma than nontransgenic littermates. Moreover, when the same TCR-transgenic mice were challenged simultaneously with B7-1(+) and B7-1(-) tumors, only B7-1(+) tumors were rejected. Therefore, even though P1A can be a tumor rejection antigen, the effector function of P1A-specific CTL is restrained in vivo. These results have important implications for the strategy of tumor immunotherapy.  (+info)

Chimerism and xenotransplantation. New concepts. (2/361)

In both transplant and infectious circumstances, the immune response is governed by migration and localization of the antigen. If the antigenic epitopes of transgenic xenografts are sufficiently altered to avoid evoking the destructive force of innate immunity, the mechanisms of engraftment should be the same as those that permit the chimerism-dependent immunologic confrontation and resolution that is the basis of allograft acceptance. In addition to "humanizing" the epitopes, one of the unanswered questions is whether the species restriction of complement described in 1994 by Valdivia and colleagues also necessitates the introduction of human complement regulatory genes in animal donors. Because the liver is the principal or sole source of most complement components, the complement quickly is transformed to that of the donor after hepatic transplantation. Thus, the need for complementary regulatory transgenes may vary according to the kind of xenograft used. Much evidence shows that physiologically important peptides produced by xenografts (e.g., insulin, clotting factors, and enzymes) are incorporated into the metabolic machinery of the recipient body. To the extent that this is not true, xenotransplantation could result in the production of diseases that are analogous to inborn errors of metabolism. In the climate of pessimism that followed the failures of baboon to human liver xenotransplantation in 1992-1993, it seemed inconceivable that the use of even more discordant donors, such as the pig, could ever be seriously entertained; however, this preceded insight into the xenogeneic and allogeneic barriers that has brought transplantation infectious immunity to common ground. With this new insight and the increasing ease of producing transgenic donors, the goal of clinical xenotransplantation may not be so distant.  (+info)

Cutting edge: negative selection of immature thymocytes by a few peptide-MHC complexes: differential sensitivity of immature and mature T cells. (3/361)

We quantitated the number of peptide-class II MHC complexes required to affect the deletion or activation of 3A9 TCR transgenic thymocytes. Deletion of immature double positive thymocytes was very sensitive, taking place with approximately three peptide-MHC complexes per APC. However, the activation of mature CD4+ thymocytes required 100-fold more complexes per APC. Therefore, a "biochemical margin of safety" exists at the level of the APC. To be activated, autoreactive T cells in peripheral lymphoid tissues require a relatively high level of peptide-MHC complexes.  (+info)

Chronic modulation of the TCR repertoire in the lymphoid periphery. (4/361)

Using TCR V beta 5 transgenic mice as a model system, we demonstrate that the induction of peripheral tolerance can mold the TCR repertoire throughout adult life. In these mice, three distinct populations of peripheral T cells are affected by chronic selective events in the lymphoid periphery. First, CD4+V beta 5+ T cells are deleted in the lymphoid periphery by superantigens encoded by mouse mammary tumor viruses-8 and -9 in an MHC class II-dependent manner. Second, mature CD8+V beta 5+ T cells transit through a CD8lowV beta 5low deletional intermediate during tolerance induction by a process that depends upon neither mouse mammary tumor virus-encoded superantigens nor MHC class II expression. Third, a population of CD4-CD8-V beta 5+ T cells arises in the lymphoid periphery in an age-dependent manner. We analyzed the TCR V alpha repertoire of each of these cellular compartments in both V beta 5 transgenic and nontransgenic C57BL/6 mice as a function of age. This analysis revealed age-related changes in the expression of V alpha families among different cellular compartments, highlighting the dynamic state of the peripheral immune repertoire. Our work indicates that the chronic processes maintaining peripheral T cell tolerance can dramatically shape the available TCR repertoire.  (+info)

Survival of naive CD4 T cells: roles of restricting versus selecting MHC class II and cytokine milieu. (5/361)

The diversity of naive CD4 T cells plays an important role in the adaptive immune response by ensuring the capability of responding to novel pathogens. In the past, it has been generally accepted that naive CD4 T cells are intrinsically long-lived; however, there have been studies suggesting some CD4 T cells are short-lived. In this report, we identify two populations of naive CD4 T cells: a long-lived population as well as a short-lived population. In addition, we identify two factors that contribute to the establishment of long-lived naive CD4 T cells. We confirm earlier findings that MHC class II interaction with the TCR on CD4 T cells is important for survival. Furthermore, we find that MHC class II alleles with the correct restriction element for Ag presentation mediate the peripheral survival of naive CD4 T cells more efficiently than other positively selecting alleles, regardless of the selecting MHC in the thymus. The second component contributing to the survival of naive CD4 T cells is contact with the cytokines IL-4 and IL-7. We find that the physiological levels of IL-4 and IL-7 serve to enhance the MHC class II-mediated survival of naive CD4 T cells in vivo.  (+info)

Two mechanisms for the non-MHC-linked resistance to spontaneous autoimmunity. (6/361)

Genetic susceptibility and resistance to most autoimmune disorders are associated with highly polymorphic genes of the MHC and with non-MHC-linked polygenic modifiers. It is known that non-MHC-linked polymorphisms can override or enhance the susceptibility to an autoimmune disease provided by pathogenic MHC genes, but the mechanisms remain elusive. In this study, we have followed the fate of two highly diabetogenic beta cell-specific T cell receptors (Kd and I-Ag7 restricted, respectively) in NOR/Lt mice, which are resistant to autoimmune diabetes despite expressing two copies of the diabetogenic MHC haplotype H-2g7. We show that at least two mechanisms of non-MHC-linked control of pathogenic T cells operate in these mice. One segregates as a recessive trait and is associated with a reduction in the peripheral frequency of diabetogenic CD8+ (but not CD4+) T cells. The other segregates as a dominant trait and is mediated by IL-4- and TGF-beta1-independent immune suppressive functions provided by lymphocytes that target diabetogenic CD4+ and CD8+ T cells, without causing their deletion, anergy, immune deviation, or ignorance. These results provide explanations as to how non-MHC-linked polymorphisms can override the susceptibility to an autoimmune disease provided by pathogenic MHC haplotypes, and demonstrate that protective non-MHC-linked genes may selectively target specific lymphoid cell types in cellularly complex autoimmune responses.  (+info)

Autoantigen-independent deletion of diabetogenic CD4+ thymocytes by protective MHC class II molecules. (7/361)

Some MHC class II genes provide dominant resistance to certain autoimmune diseases via mechanisms that remain unclear. We have shown that thymocytes bearing a highly diabetogenic, I-Ag7-restricted beta-cell-reactive TCR (4.1-TCR) undergo negative selection in diabetes-resistant H-2g7/x mice by engaging several different antidiabetogenic MHC class II molecules on thymic (but not peripheral) hemopoietic cells, independently of endogenous superantigens. Here we have investigated 1) whether this TCR can also engage protective MHC class II molecules (I-Ab) on cortical thymic epithelial cells in the absence of diabetogenic (I-Ag7) molecules, and 2) whether deletion of 4.1-CD4+ thymocytes in I-Ab-expressing mice might result from the ability of I-Ab molecules to present the target beta-cell autoantigen of the 4.1-TCR. We show that, unlike I-Ag7 molecules, I-Ab molecules can restrict neither the positive selection of 4.1-CD4+ thymocytes in the thymic cortex nor the presentation of their target autoantigen in the periphery. Deletion of 4.1-CD4+ thymocytes by I-Ab molecules in the thymic medulla, however, is a peptide-specific process, since it can be triggered by hemopoietic cells expressing heterogeneous peptide/I-Ab complexes, but not by hemopoietic cells expressing single peptide/I-Ab complexes. Thus, unlike MHC-autoreactive or alloreactive TCRs, which can engage deleting MHC molecules in the thymic cortex, thymic medulla, and peripheral APCs, the 4.1-TCR can only engage deleting MHC molecules (I-Ab) in the thymic medulla. We therefore conclude that this form of MHC-induced protection from diabetes is based on the presentation of an anatomically restricted, nonautoantigenic peptide to highly diabetogenic thymocytes.  (+info)

Negative selection of immature B cells by receptor editing or deletion is determined by site of antigen encounter. (8/361)

Immature B cells that encounter self-antigen are eliminated from the immune repertoire by negative selection. Negative selection has been proposed to take place by two distinct mechanisms: deletion by apoptosis or alteration of the antigen receptor specificity by receptor editing. While convincing evidence exists for each, the two models are inherently contradictory. In this paper, we propose a resolution to this contradiction by demonstrating that the site of first antigen encounter dictates which mechanism of negative selection is utilized. We demonstrate that the bone marrow microenvironment provides signals that block antigen-induced deletion and promote RAG reinduction. In the periphery, the absence of these signals allows the immature B cell to default to apoptosis as a result of BCR engagement.  (+info)

Looking for online definition of clonal deletion theory in the Medical Dictionary? clonal deletion theory explanation free. What is clonal deletion theory? Meaning of clonal deletion theory medical term. What does clonal deletion theory mean?
The role of BAFF in B cell self tolerance was examined by tracking the fate of anti-HEL self-reactive B cells in BAFF transgenic mice using four different models of self-reactive B cell deletion. BAFF overexpression did not affect the development of self-reactive B cells normally deleted in the bone marrow or during the early stages of peripheral development. By contrast, self-reactive B cells normally deleted around the late T2 stage of peripheral development were rescued from deletion, matured, and colonized the splenic follicle. Furthermore, self-reactive B cells normally selectively deleted from the marginal zone repopulated this compartment when excess BAFF was present. Self-reactive B cells rescued by excess BAFF were not anergic. BAFF overexpression therefore rescued only self-reactive B cells normally deleted with relatively low stringency and facilitated their migration into otherwise forbidden microenvironments. This partial subversion of B cell self tolerance is likely to underlie the
In this work, we have shown that overexpression of Bcl-2 protects peripheral CD8 T cells from deletion in response to cross-presented self antigen. The OT-I.Eμ-Bcl-2 and OT-I.vav.Bcl-2 cells appeared similar to wild-type OT-I cells in their ability to be activated and proliferate in response to cross-presented self-antigen. If sufficiently high numbers of OT-I.Eμ-Bcl-2 T cells were transferred, they induced autoimmune diabetes (Table I). As a pro-survival molecule Bcl-2 protects lymphocytes in vitro and in vivo against apoptosis induced by growth factor deprivation, DNA damage or treatment with corticosteroids or calcium ionophores (16). For activated T cells in vivo, bcl-2 transgene expression prolongs T cell survival following injection of mice with the superantigen staphylococcus enterotoxin B (SEB; reference 16), the transfer of HY-TCR CD8 T cells into male recipients (18), the immunization of mice expressing a transgenic LCMV-TCR in CD8 T cells with LCMV peptide (19) and the immunization ...
Little is know about the nature of peripheral B cell tolerance or how it may vary in distinct lineages. Although autoantibody transgenic studies indicate that anergy and apoptosis are involved, some studies claim that receptor editing occurs. To model peripheral B cell tolerance in a normal, polyclonal immune system, we generated transgenic mice expressing an Igκ-light chain-reactive superantigen targeted to the plasma membrane of hepatocytes (pAlb mice). In contrast to mice expressing κ superantigen ubiquitously, in which κ cells edit efficiently to λ, in pAlb mice, κ B cells underwent clonal deletion. Their κ cells failed to populate lymph nodes, and the remaining splenic κ cells were anergic, arrested at a semi-mature stage without undergoing receptor editing. In the liver, κ cells recognized superantigen, down-regulated surface Ig, and expressed active caspase 3, suggesting ongoing apoptosis at the site of B cell receptor ligand expression. Some, apparently mature, κ B1 and ...
The developmental pathway that TCRαβ+CD8αα+ intestinal intraepithelial lymphocytes (here called unconventional iIEL) follow has long remained a mystery. In their recent paper, McDonald et al. cloned and forced the expression of TCRs isolated from unconventional iIEL and came to the following conclusions. First, TCR specificity drives commitment to the unconventional iIEL lineage. Second, iIEL TCRs induce a pattern of thymic negative selection, with most cells expressing these TCR undergoing apoptosis but a small proportion of them escaping deletion and selectively maturing into unconventional iIEL. Third, the post-selection precursors to unconventional iIEL are the CD4loCD8lo(DPlo)CD69hiPD-1hi thymocytes, a population that largely overlaps with the general pool of MHC class I- or MHC class II-autoreactive thymocytes that undergo negative selection. By downregulating the expression of both CD4 and CD8b coreceptors, these cells largely lose their ability to recognize self ligands and, instead ...
There is clear evidence that tumor patients are able to generate TAA-specific T cell immunity spontaneously. Whereas the presence of tumor-specific T cells has been shown by many groups and for various tumor types, much less is known about the function of TAA-specific T cells in vivo. Most of the TAAs including differentiation, germ-line, and shared overexpressed antigens are not tumor specific but are also expressed at low levels in certain nonmalignant tissues. This should influence the type of T cell response because deletion of functional high-avidity self-reactive T cells in the thymus as well as peripheral deletion or anergy was shown in various animal models (reviewed in Ref. 74 ). There are a few recent studies analyzing the functional avidity of TAA-specific T cells in patients. In leukemia patients, low-avidity T cells to proteinase 3, which are able to kill leukemia cells, can readily be expanded. However, high-avidity T cells can also be expanded from patients in cytogenetic ...
Studies using the 4.1 TCR transgenic system found thymic or peripheral deletion as well as anergy and ignorance do not contribute to CD4 T-cell tolerance induction in NOR mice (13). Similarly, we found the frequency and proliferative capacity of BDC2.5-like CD4 T-cells was comparable in NOD and NOR mice. The fact that NOR CD4 T-cells induced type 1 diabetes in some NOD.CD4null recipients revealed the retention of at least minimal pathogenic activity. On the other hand, NOR T-cells are more susceptible than those from NOD mice to activation-induced cell death (AICD) (34). Therefore, abortive activation followed by AICD may limit the effector function of NOR diabetogenic CD4 T-cells. Another nonmutually exclusive possibility is that diabetogenic CD4 T-cells are more efficiently suppressed in NOR than NOD mice. However, we found no difference in the frequency or in vitro suppressive function between NOD and NOR Tregs. These results suggested that Treg function and the sensitivity of effector ...
The immune procedure has been identified to have the ability to distinguishing self from non-self because the pioneering paintings of Paul Erhlich greater than a century in the past. initially defined in experiments learning blood transfusion comp- ibility, the primary of horror autotoxicus continues to be legitimate, even supposing this present day the phenomenon is mostly defined by way of tolerance or lack of awareness. greatly has been discovered concerning the a variety of procedures fighting self-reactivity usually. those comprise strategies that function in the course of immune mobilephone ontogeny and for that reason on reactivity of mature lymphocytes within the outer edge. They surround mechanisms which are intrinsic to most likely reactive lymphocytes and will lead to primary or peripheral deletion or the alteration of sensible power. furthermore, there are in?uences which are extrinsic to almost certainly auto-reactive lymphocytes, together with the functionality of regulatory ...
Plant-based diets may be protective against multiple sclerosis because IGF-1 can prevent our immune system from eliminating autoimmune cells.
Non- H-2 genes responsible for negative selection of Tcrb-V 11+ T cells were examined using backcross mice of various strains with C58, which does not delete Tcrb-V 11+ T cells. Two independently segr
The findings here demonstrate that selectively restoring B7.2 expression on otherwise self-tolerant B cells is sufficient to switch their fate from peripheral deletion to large-scale proliferation and autoantibody secretion during interactions with specific CD4+ T cells. Of the many early signals and responses to BCR engagement that are repressed or altered in tolerant B cells ((12)-(14)), the data here single out repression of the B7.2 response as being necessary to allow peripheral tolerance by FasL/Fas-mediated clonal abortion. The findings raise interesting questions about how B7.2 switches the outcome of interactions between tolerant B and T cells, and highlight the regulation of B7.2 in B cells as a key process that may be dysregulated by inherited or acquired triggers to systemic autoimmune disease.. Three possible mechanisms may in principle explain how dysregulated expression of B7.2 on tolerant B cells switches the outcome of interactions with autoantigen-specific T cells from deletion ...
Recognition of self-antigens is required for regulatory T (Treg) cells to exert dominant tolerance. However, the mechanism by which self-reactive thymocytes are diverted into the Treg cell subset is unclear. To address this question, we looked for the immediate precursors to Treg cells within Foxp3( …
TY - JOUR. T1 - Establishment of the Major Compatibility Complex-Dependent Development of CD4+ and CD8+ T Cells by the Cbl Family Proteins. AU - Huang, Fang. AU - Kitaura, Yasuyuki. AU - Jang, Ihn Kyung. AU - Naramura, Mayumi. AU - Kole, Hemanta H H.. AU - Liu, Liping. AU - Qin, Haiyan. AU - Schlissel, Mark S S.. AU - Gu, Hua. PY - 2006/10. Y1 - 2006/10. N2 - Casitas B cell lymphoma (Cbl) proteins are negative regulators for T cell antigen receptor (TCR) signaling. Their role in thymocyte development remains unclear. Here we show that simultaneous inactivation of c-Cbl and Cbl-b in thymocytes enhanced thymic negative selection and altered the ratio of CD4+ and CD8+ T cells. Strikingly, the mutant thymocytes developed into CD4+- and CD8+-lineage T cells independent of the major histocompatibility complex (MHC), indicating that the CD4+- and CD8+-lineage development programs are constitutively active in the absence of c-Cbl and Cbl-b. The mutant double-positive (DP) thymocytes exhibited ...
CD30 is a type I transmembrane glycoprotein of the TNF receptor superfamily. CD30 was originally identified as a cell surface antigen of Hodgkins and Reed-Sternberg cells using monoclonal antibody Ki-1. The ligand for CD30 is CD30L (CD153). The binding of CD30 to CD30L mediates pleiotropic effects including cell proliferation, activation, differentiation, and apoptotic cell death. CD30 has a critical role in the pathophysiology of Hodgkins disease and other CD30+ lymphomas. CD30 acts as a costimulatory molecule in thymic negative selection. In addition to its expression on Hodgkins and Reed-Sternberg cells, CD30 is also found in some non-Hodgkins lymphomas (including Burkitts lymphomas), virus-infected T and B cells, and on normal T and B cells after activation. In T cells, CD30 expression is present on a subset of T cells that produce Th2-type cytokines and on CD4+/CD8+ thymocytes that co-express CD45RO and the IL4 receptor. Soluble form of CD30 (sCD30) serves as a marker reflecting Th2 ...
CD4+ Foxp3+ regulatory T (Treg) cells belong to a distinct T cell lineage which develops in the thymus and is essential for the prevention of self-reactivity by suppressing peripheral auto-reactive T cells that escape thymic negative selection. IL-2/IL-2R signaling is crucial and non-redundant for the development of thymic Treg cells, as well as the homeostasis and competitive fitness of peripheral Treg cells. The central role of IL-2 in Treg biology is exemplified by the uncontrolled massive lymphoproliferation associated with IL-2-/-, IL-2Rα-/- and IL-2Rβ-/- mice which typically die by 4-12 week of age. It is noteworthy that a restored normal percentage and number of peripheral Treg cells in Bim-/- IL-2-/- mice did not rescue these mice from severe autoimmunity. Instead, additional IL-2 was still required for the proper functioning of peripheral Bim-/- IL-2-/- Treg cells. Consistently, in the current studies, we found that the development of thymic Treg cells was blocked with mostly CD4+ CD25-
Clonal deletion of autoreactive T cells in the thymus is not the sole mechanism for the induction of tolerance to self-antigens since partial depletion of peripheral CD4(+) T cells from neonatal and adult animals results in the development of organ-specific autoimmunity. Reconstitution of these immu …
Isolation of human CD4+ T cells by negative selection using EasySep™ to separate highly purified cells in as little as 8 minutes
The cell surface receptor Fas (FasR, Apo-1, CD95) and its ligand (FasL) are mediators of apoptosis that have been shown to be implicated in the peripheral deletion of autoimmune cells, activation-induced T cell death, and one of the two major cytolytic pathways mediated by CD8+ cytolytic T cells. To gain further understanding of the Fas system., we have analyzed Fas and FasL expression during mouse development and in adult tissues. In developing mouse embryos, from 16.5 d onwards, Fas mRNA is detectable in distinct cell types of the developing sinus, thymus, lung, and liver, whereas FasL expression is restricted to submaxillary gland epithelial cells and the developing nervous system. Significant Fas and FasL expression were observed in several nonlymphoid cell types during embryogenesis, and generally Fas and FasL expression were not localized to characteristic sites of programmed cell death. In the adult mouse, RNase protection analysis revealed very wide expression of both Fas and FasL. ...
The cell surface receptor Fas (FasR, Apo-1, CD95) and its ligand (FasL) are mediators of apoptosis that have been shown to be implicated in the peripheral deletion of autoimmune cells, activation-induced T cell death, and one of the two major cytolytic pathways mediated by CD8+ cytolytic T cells. To gain further understanding of the Fas system., we have analyzed Fas and FasL expression during mouse development and in adult tissues. In developing mouse embryos, from 16.5 d onwards, Fas mRNA is detectable in distinct cell types of the developing sinus, thymus, lung, and liver, whereas FasL expression is restricted to submaxillary gland epithelial cells and the developing nervous system. Significant Fas and FasL expression were observed in several nonlymphoid cell types during embryogenesis, and generally Fas and FasL expression were not localized to characteristic sites of programmed cell death. In the adult mouse, RNase protection analysis revealed very wide expression of both Fas and FasL. ...
Dear Immunonetters, I would like to bring another player into the Self/non-self discrimination arena. That Being the effect of Anergic T-cells on other autoreactive T-cells.This concept has been discussed in the papers by Lasalle and Hafler ( FASEB J. 8:601-608 1994) and Lombardi et al ( science 264:1587 1994). I agree with the authors that the Anergic T-cells play an important rolein self/nonself discrimination. In summary this is whats happening. The Thymus, site of clonal deletion, is very efficient in removing autoreactive T-cells. But nothing is perfect and some autoreactive cells escape this screening. These T-cells can be safely present in the periphery if the antigens they are reactive to are hidden away from them or not presented to them. This is called Clonal Ignorance. If MHC/AG is presented to the autoreactive T-cell but is not followed by costimulation, the result is Clonal anergy. In these cases the T-cells can recognize the self antigen however the extent of the response stops ...
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Dendritic cells (DCs) are known to regulate immune responses by inducing both central and peripheral tolerance. DCs play a vital role in negative selection of developing thymocytes by deleting T cells with high-affinity for self-peptide-major histocompatibility complexes. In the periphery, DCs mediate peripheral tolerance by promoting regulatory T-cell development, induction of T-cell unresponsiveness, and deletion of activated T cells. We studied whether allogeneic DCs, obtained from bone marrow cultured with either Flt3L (FLDCs) or granulocyte-macrophage colony-stimulating factor (GMDCs), could induce allospecific central and peripheral tolerance after IV injection; B cells were used as a control. The results showed that only FLDCs reached the thymus after injection and that these cells induced both central and peripheral tolerance to donor major histocompatibility complexes. For central tolerance, injection of FLDCs induced antigen-specific clonal deletion of both CD8 and CD4 single-positive
An amphetamine tolerance can cause a person to take more amphetamines than they really need, and can cause their body to become dependent then addicted.
In a healthy individual, the immune system uses several different immune tolerance mechanisms in order to prevent the development of autoimmune disease. For T c...
If your not confident, buythe parts and bring it to Leeds, I will do it for you. It would be most of the day. If not here goes. 1) you have to be sure thats the problem. 2) How many hours has the
In this project we propose to determine the role of candidate G protein-coupled receptors (GPCRs) in enforcing deletion of developing auto-reactive T cells in t...
Deletion of autoreactive thymocytes at the DP stage is the basis for tolerance to thymus-expressed self antigens. In this study we investigated whether distinct signalling pathways are induced in DP thymocytes as compared to mature T cells upon stimulation with antigen. Using triple transgenic mice expressing a TCR transgene, dominant negative ras/Mek proteins and a reporter gene construct with AP-1 or NF-kappa B binding sites, we showed a complete lack of transcriptional activity of NF-kappa B but not AP-1 in DP thymocytes, whereas both were transcriptionally active in mature T cells after antigenic stimulation. Lack of NF-kappa B induction correlated with increased death in response to antigen. AP-1 induction was dependent on the integrity of the ras/Mek pathway indicating that this pathway was activated in the DP thymocytes. In contrast, we found a complete lack of constitutive expression of the epsilon isoform of Protein Kinase C (PKC) in DP thymocytes, although it was present in mature thymocytes
TY - JOUR. T1 - Cell deletion by apoptosis during regression of rat parotid sialadenosis. AU - Chisholm, D. M.. AU - Adi, M. M.. AU - Ervine, I. M.. AU - Ogden, G. R.. PY - 1995. Y1 - 1995. N2 - parotidtoplasmicl:lnuclearEnlargement of the rat parotid salivary glands was induced by repeated administration of isoproterenol. Mean wet weights of the treated glands increased steadily to 240% of control values. Following withdrawal of the drug, quantitative histological techniques were used to investigate the balance between hypertrophy, hyperplasia and apoptosis. The volume occupied by acinar cells relative to the total gland volume together with cytoplasmic:nuclear area ratios as measures of hypertrophy increased during the early experimental period. Similarly, serous acinar cell mitotic counts increased, indicating that hyperplasia had occurred. Apoptosis was demonstrated at light microscopical level to be the main mechanism for cell deletion as the glands returned to normal size and weight, The ...
Mentor: Nina Luning Prak, MD, PhD, University of Pennsylvania School of Medicine. Aberrant light chain rearrangement has been implicated in the loss of tolerance in self-reactive B cells. Ongoing light chain rearrangement, a process termed receptor editing, is a major mechanism for tolerizing self-reactive B cells. We have observed that highly edited B cells become less frequent once fully assembled antibody molecules are expressed on the B cell surface. We hypothesized that the decrease in highly edited B cells is due either to negative selection (death of cells that have failed to edit successfully), positive selection of cells with fewer rearrangements or escape of edited B cells to a hitherto unidentified peripheral compartment. Here, we report preliminary data from a pilot experiment that macrophages may be involved in the selective depletion of highly edited B cells. Flow cytometry analysis revealed co-expression of macrophage markers, F4/8 and CD-11, in anti-DNA heavy chain knock-in mouse ...
Figure 10. Killer T-cells eliminate intracellular pathogens. Intracellular pathogens are eliminated by a specialized type of lymphocyte, called a killer T-cell (see figure 10. Killer T-cells are a subclass of T-cells, meaning that they mature in the thymus, are tolerized via clonal deletion, and do not hypermutate when cloning. Killer T-cells bind not to simple proteins, but to proteins held by MHC molecules. In other words, killer T-cells can only recognize proteins expressed by MHC on the surface of host cells. If a killer T-cell is activated by recognition of a MHC/protein combination, it will kill the infected host cell. There are many ways in which this is done, e.g. killer T-cells can punch holes in cell walls, or secrete chemicals that destroy cell walls, etc. NEXT: Summary ...
Here are some very clear clips for the immune responses to infection, starting with a really well done explanation of Burnets Nobel-winning clonal selection theory: If you like that, check out some more of the videos from the Walter and Eliza Hall Institute of Medical Research. Try this animation and quiz: McGraw Hill Online Centre…
A clonal chromosome deletion 2p21 was found in endomyometriosis by Verhest et al. while Pai evidenced a strict relationship ... Verhest A, Simonart T, Noel JC (1996). A unique clonal chromosome 2 deletion in endomyometriosis. Cancer Genet Cytogenet 1996; ...
"Intrathymic and extrathymic clonal deletion of T cells." Current opinion in immunology 7.2 (1995): 196-205. Crotty, Shane, et ... The memory B cell has already undergone clonal expansion, differentiation and affinity maturation, so it is able to divide ...
"Resolving the Enigma of the Clonal Expansion of mtDNA Deletions". Genes (Basel). 9 (3): 126. doi:10.3390/genes9030126. PMC ...
They were also shown to be more efficient in T regulatory cells selection than clonal deletion. The last abundant subset of ... Bonasio R, Scimone ML, Schaerli P, Grabie N, Lichtman AH, von Andrian UH (October 2006). "Clonal deletion of thymocytes by ... Experiments from this study reveal that clonal deletion of autoreactive CD4+ T cells, apart from CD8+ T cells, requires ... Two processes of central tolerance take place in thymic medulla, namely clonal deletion (recessive tolerance) and T Regulatory ...
"Autoreactive T cells escape clonal deletion in the thymus by a CD24-dependent pathway". Journal of Immunology. 181 (1): 320-8. ...
Both clonal anergy and clonal deletion have been shown to operate in vetoed T cells. The veto cell need only carry the self-MHC ... Avoiding self-reactivity in the T cell compartment is maintained by: clonal deletion in the thymus and suppressive cells that ... "Deletion of cognate CD8 T cells by immature dendritic cells: a novel role for perforin, granzyme A, TREM-1, and TLR7". Blood. ... evidence for a deletion-based mechanism mediated by TNF-alpha". Blood. 105 (6): 2585-93. doi:10.1182/blood-2002-11-3463. PMID ...
Most T cells are, in time, eliminated in the thymus by a process of clonal deletion. However, some of them escape this process ...
Just as in T cells, clonal deletion and clonal anergy can physically eliminate autoreactive B cell clones. Receptor editing is ... This negative selection is known as clonal deletion, one of the mechanisms for B cell tolerance. Approximately 99 percent of ... The mechanism of clonal anergy is important to maintain tolerance to many autologous antigens. Active suppression is the other ... This same positive and negative selection mechanism, but in peripheral tissues, is known as clonal anergy. ...
If they bind a self peptide, then they are signaled to apoptose (process of clonal deletion). The thymic epithelial cells ... clonal deletion) Receptor editing: the self-reactive B cell changes specificity by rearranging genes and develops a new BCR ... The results were explained by Burnet's clonal selection hypothesis. Burnet and Medawar won the Nobel Prize in 1960 for their ...
Both activated T cells and B cells express Fas and undergo clonal deletion by the AICD mechanism. Activated T cells that ...
This can induce T cell clonal deletion, T cell anergy or the proliferation of regulatory T cells (Tregs). Collectively, these ...
In either case, the B cell is allowed to proliferate or is killed off through a process called clonal deletion. Normally, the ...
Nature 333, 742-746 (1988); Swat, W., Ignatowicz, L., von Boehmer, H. and Kisielow, P.: Clonal deletion of immature CD4+8+ ... Nature 351, 150 (1991). Central tolerance by deletion of immature T cells in TCR transgenic mice. Teho H. S., Kisielow, P., ... Science 251, 1225 (1991). Peripheral tolerance by deletion of and reversible anergy in matureT cells. Borgulya, P., Kishi, H., ...
... evidence against clonal deletion as the mechanism of tolerance induction". Scandinavian Journal of Immunology. 8 (1): 29-37. ...
It was published that mTECs mediate clonal deletion (recessive tolerance), via presentation of TRAs, which leads to the ... namely clonal deletion or T regulatory cells selection, respectively. N.B.: All the below cited references utilized mouse as a ... that specific TRAs skew autoreactive T cells into TRegs with much higher efficiency than they do in the case of clonal deletion ... Rossi SW, Jenkinson WE, Anderson G, Jenkinson EJ (June 2006). "Clonal analysis reveals a common progenitor for thymic cortical ...
Tolerogenic DCs are essential in maintenance of central and peripheral tolerance through induction of T cell clonal deletion, T ... These tolerogenic properties are executed by deletion of T cells, induction of Tregs and anergized T cells, then by expression ...
... clonal deletion, receptor editing, anergy, or ignorance (B cell ignores signal and continues development). This negative ...
... who were the first to propose the deletion of self-reactive lymphocytes to establish tolerance, now termed clonal deletion. ... The deletion threshold is much more stringent for T cells than for B cells since T cells alone can cause direct tissue damage. ...
... most mother's fetal-specific CD8+ T cells undergo clonal deletion and express low levels of chemokine receptors and ligands - ...
... clonal anergy, deletion, and ignorance. While autoimmunity is thought to result from the breakdown of central and peripheral ... This mutant form of the anti-CD3 acts by only delivering a partial signal to the T-cell, leading to inactivation, deletion, and ... although a few T-cells will escape thymic deletion. However, these potentially self-reactive cells in the periphery are held in ...
... demonstrating that neither thymus nor clonal deletion is necessary to induce tolerance. In 1989 was successfully induced ...
... clonal anergy MeSH G04.610.484.120 - clonal deletion MeSH G04.610.484.800 - self tolerance MeSH G04.610.484.910 - tachyphylaxis ...
Clonal deletion theory, proposed by Burnet, according to which self-reactive lymphoid cells are destroyed during the ... Pike B, Boyd A, Nossal G (1982). "Clonal anergy: the universally anergic B lymphocyte". Proceedings of the National Academy of ... Consequently, auto-reactive B cells, that escape deletion, cannot find the antigen or the specific helper T cell. Suppressor ... In addition, two other theories are under intense investigation: Clonal ignorance theory, according to which autoreactive T ...
Clonal anergy Clonal deletion Clonal selection Clone (cell biology) CMKLR1 Colony stimulating factor 1 receptor Colony- ...
Autoimmunity Alloimmunity Cross-reactivity Tolerance Central tolerance Peripheral tolerance Clonal anergy Clonal deletion ... Mimotope Tumor antigen Antigen-antibody interaction Immunogenetics Affinity maturation Somatic hypermutation Clonal selection V ...
... ignorance of antigen and direct inactivation of effector T cells by either clonal deletion, conversion to regulatory T cells ( ... Deletion of self-reactive T cells in the thymus is only 60-70% efficient, and naive T cell repertoire contains a significant ... There are also extrinsic mechanisms of deletion mediated by the cytotoxic activity of Fas/FasL or TRAIL/TRAILR interaction. ...
... also called clonal anemone Vegetative cloning, a form of asexual reproduction in plants Clonal reproduction Clonal deletion, a ... Look up clonal in Wiktionary, the free dictionary. Clonal may refer to: Clonal interference, a phenomenon that occurs when two ... a model for how the immune system responds to infection Clonal anergy, a lack of reaction by the body's defense mechanisms to ... Cloning This disambiguation page lists articles associated with the title Clonal. If an internal link led you here, you may ...
... the others being clonal deletion and immunoregulation). This phenomenon was first described in B lymphocytes by Gustav Nossal ... "clonal selection"). This specific clonal army then combats the pathogen until the body is free of the infection. Following ... The clonal expansion of those cells can lead to autoimmune diseases, wherein the body attacks itself. In order to prevent this ... This process - called "clonal expansion" - allows the body to quickly mobilise an army of clones, as and when required. Such ...
Thus, clonal deletion can help protect individuals against autoimmunity. Clonal deletion is thought to be the most common type ... Incomplete clonal deletion results in apoptosis of most autoreactive B and T lymphocytes. Complete clonal deletion can lead to ... T lymphocytes can instead undergo clonal arrest, clonal anergy, and clonal editing. If autoreactive cells escape clonal ... In immunology, clonal deletion is the removal through apoptosis of B cells and T cells that have expressed receptors for self ...
... acquires a strong selective advantage creating a clinically apparent clonal population harboring the same pattern of deletions ... reported on a case in which chromothripsis, normally a catastrophic event in which chromosomes undergo massive deletion and ...
Clonal deletion. *Tolerance in pregnancy. *Immunodeficiency. *Immune privilege. Immunogenetics. *Affinity maturation *Somatic ...
Clonal deletion. *Tolerance in pregnancy. *Immunodeficiency. *Immune privilege. Immunogenetics. *Affinity maturation *Somatic ...
Activity of ABL1 protein is negatively regulated by its SH3 domain, and deletion of the SH3 domain turns ABL1 into an oncogene ... leading to a clonal myeloproliferative disorder. The BCR-ABL protein can be inhibited by various small molecules. One such ...
1p36 deletion syndrome Chromosome 1, deletion q21 q25 Chromosome 1, duplication 1p21 p32 Chromosome 1, monosomy 1p Chromosome 1 ... ectropion conical teeth Cleidocranial dysplasia Cleidocranial dysplasia micrognathia absent thumbs Cloacal exstrophy Clonal ... deletion 11p Chromosome 11, partial trisomy 11q Chromosome 11-14 translocation Chromosome 11p, partial deletion Chromosome 11q ... deletion 14q, partial duplication 14p Chromosome 14, trisomy mosaic Chromosome 14q, partial deletions Chromosome 14q, proximal ...
2006). "6q deletion discriminates Waldenström macroglobulinemia from IgM monoclonal gammopathy of undetermined significance". ... Waldenström macroglobulinemia is characterized by an uncontrolled clonal proliferation of terminally differentiated B ... Comparative genomic hybridization identified the following chromosomal abnormalities: deletions of 6q23 and 13q14, and gains of ... and small somatic deletions associated with B-cell lymphomagenesis". Blood. 123 (11): 1637-46. doi:10.1182/blood-2013-09-525808 ...
ln clonal populations of Paramecium, aging occurs over successive generations leading to a gradual loss of vitality, unless the ... and so in addition to deletion, DNA inversion and translocation are required for "unscrambling". This process is guided by long ... The basis for clonal aging was clarified by the transplantation experiments of Aufderheide in 1986 who demonstrated that the ... Additional experiments by Smith-Sonneborn, Holmes and Holmes, and Gilley and Blackburn demonstrated that, during clonal aging, ...
Clonal populations of bacteria, each population maintaining a single artificial chromosome, are stored in various laboratories ... Examples of diseases that are diagnosed using FISH include Prader-Willi syndrome, Angelman syndrome, 22q13 deletion syndrome, ... these mixtures are used to detect deletion mutations. When combined with a specific color, a locus-specific probe mixture is ...
DNMT3a is the gene most commonly found mutated in clonal hematopoiesis, a common aging-related phenomenon in which ... Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens ... Sperling, Adam S.; Gibson, Christopher J.; Ebert, Benjamin L. (2017). "The genetics of myelodysplastic syndrome: from clonal ... Jan, Max; Ebert, Benjamin L.; Jaiswal, Siddhartha (1 January 2017). "Clonal hematopoiesis". Seminars in Hematology. 54 (1): 43- ...
Large-scale mutations involve the deletion or gain of a portion of a chromosome. Genomic amplification occurs when a cell gains ... Clonal evolution leads to intra-tumour heterogeneity (cancer cells with heterogeneous mutations) that complicates designing ... Small-scale mutations include point mutations, deletions, and insertions, which may occur in the promoter region of a gene and ... Murgia C, Pritchard JK, Kim SY, Fassati A, Weiss RA (August 2006). "Clonal origin and evolution of a transmissible cancer". ...
The ΔF508 mutation is a deletion of the C-G pair from position 507 along with the first two T-A pairs from position 508, ... Cell engineering methods including fluorogenic oligonucleotide signaling probes may be used to detect and isolate clonal cell ... The most common mutation, called ΔF508, is a deletion (Δ) of one amino acid (phenylalanine) at position 508 in the CFTR protein ... The most common mutation, DeltaF508 (ΔF508) primarily known as a processing mutation which results from a deletion (Δ) of three ...
2004). "CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and ... A medically important aspect of the FIP1L1 gene is its fusion with other genes to form fusion genes which cause clonal ... In humans, an interstitial chromosomal deletion of about 800 kilobases at 4q12 deletes the CHIC2 gene (i.e.cysteine rich ... The FIP1L1-PDGFRA mutation was the first description of a gain of function mutation resulting from an interstitial deletion ...
Chambers, Henrietta L.; Hummer, Kim E. (1994). "Chromosome Counts in the Mentha Collection at the USDA: ARS National Clonal ... citing three shared insertion and deletion mutations between the species, as well as morphological and ecological similarities ...
... deletion of chromosome 13q is associated with a median OS of 17 years; and trisomy of chromosome 12, as well as deletion of ... In addition, all the CLL cells within one individual are clonal, that is, genetically identical. In practice, this is inferred ...
18q deletion syndrome Acrodermatitis enteropathica Acrogeria (Gottron syndrome) Acrokeratosis verruciformis (acrokeratosis ... Clonal seborrheic keratosis Common seborrheic keratosis (basal cell papilloma, solid seborrheic keratosis) Cowden syndrome ( ...
... (MMR) is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of ... of the somatic mutations found in mutator phenotype human colorectal tumors occur before the onset of terminal clonal expansion ...
October 2011). "Deletion of Tet2 in mice leads to dysregulated hematopoietic stem cells and subsequent development of myeloid ... July 2017). "Clonal Hematopoiesis and Risk of Atherosclerotic Cardiovascular Disease". The New England Journal of Medicine. 377 ... Mutations in this gene were first identified in myeloid neoplasms with deletion or uniparental disomy at 4q24. TET2 may also be ... as a consequence of clonal hematopoiesis. Loss-of-function due to somatic variants are frequently reported in cancer, however ...
T cells are initially resistant to Fas-mediated apoptosis during clonal expansion, but become progressively more sensitive the ... Lakins MA, Ghorani E, Munir H, Martins CP, Shields JD (2018). "Cancer-associated fibroblasts induce antigen-specific deletion ...
The disease is now classified by the World Health Organization as one form of clonal eosinophilia. It is critical that the ... Human chromosome 5 deletions that remove three adjacent genes, those for granulocyte-macrophage colony-stimulating factor, ... Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies. The PDGFRB gene is located on ... Other genetic abnormalities in PDGFRB lead to various forms of potentially malignant bone marrow disorders: small deletions in ...
A CNV or CNA could be due to a deletion or amplification of a locus with respect to the number of copies of the reference locus ... and it is routinely used for clonal amplification of samples for next-generation sequencing. The polymerase chain reaction ... was achieved by diluting DNA samples from a normal human cell line with DNA from a mutant line having a homozygous deletion of ...
Over large evolutionary timescales there would occur tandem duplication, mutations, insertions, deletions and rearrangements ... in the numbers of metastases per mouse despite the best attempts to keep the experimental conditions within each clonal group ...
Through natural or artificial selection, this method of DNA partitioning in the somatic genome can lead to clonal cell lines ... 2013). "Selecting one of several mating types through gene segment joining and deletion in Tetrahymena thermophila". PLOS ... these minichromosomes are un-equally divided between the clonal daughter cells. ...
Further, clonal pattern of MCV insertions into MCC cell genomes indicates that the virus was present in the Merkel cell before ... "Frequent detection of Merkel cell polyomavirus in human Merkel cell carcinomas and identification of a unique deletion in the ... "Clonal integration of a polyomavirus in human Merkel cell carcinoma". Science. 319 (5866): 1096-100. Bibcode:2008Sci...319.1096 ...
For example, in yeast more than 60% of spontaneous single-base pair substitutions and deletions are likely caused by ... Linhart, Yan; Janet Gehring (2003). "Genetic Variability and its Ecological Implications in the Clonal Plant Carex scopulurum ...
Eto, M., Mayumi, H., Tomita, Y., Yoshikai, Y., and Nomoto, K. (1990). Intrathymic clonal deletion of V beta 6+ T cells in ... van Meerwijk, J. P. M., and MacDonald, H. R. (1999). In vivo T lymphocyte tolerance in the absence of thymic clonal deletion ... Bonasio, R., Scimone, M. L., Schaerli, P., Grabie, N., Lichtman, A. H., and von Andrian, U. H. (2006). Clonal deletion of ... Pircher, H., Muller, K. P., Kyewski, B. A., and Hengartner, H. (1992). Thymocytes can tolerize thymocytes by clonal deletion in ...
Deletion (21)(q21.2q22.12) as a sole clonal cytogenetic abnormality in a lobular capillary hemangioma of the nasal cavity. ... 10, 11] underlying microscopic arteriovenous malformations, production of angiogenic factors, and cytogenetic clonal deletion ...
Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients. ... SHINE: Protein Language Model based Pathogenicity Prediction for Inframe Insertion and Deletion Variants ...
Clonal expansion of mtDNA deletions in skeletal muscle: new insights into mechanisms. In: Mitochondria Research Society/United ... Preferential amplification of a human mitochondrial DNA deletion in vitro and in vivo. Scientific Reports 2018, 8(1), 1799. ... Ultrasensitive deletion detection links mitochondrial DNA replication, disease, and aging. Genome Biology 2020, 21(1), 248. ... Triple real-time PCR - an improved method to detect a wide spectrum of mitochondrial DNA deletions in single cells. Scientific ...
These checkpoints also safeguard against autoimmunity by clonal deletion of autoreactive B cells that exhibit excessive BCR- ... of BCR signaling results in the clonal deletion and cell death. Several oncogenic drivers in B-cell malignancies constitutively ... In strong contrast, SHIP1 inhibition or genetic deletion of INPP5D in BCR-ABL1-driven pre-B ALL mimics excessively strong ... Similarly, frame-shifts, as well as other translationally-inactivating deletions and insertions in the INPP5D gene, occur in T- ...
The process occurs in different locations through clonal inactivation or clonal deletion.2 Central tolerance is the initial ... Blackman MA, Gerhard-Burgert H, Woodland DL, et al. A role for clonal inactivation in T cell tolerance to Mls-1a. Nature. 1990; ...
... and a greater risk of developing clonal chromosome 7 deletions leading to MDS and AML. We recently demonstrated that expressing ... The cover image shows nonrandom chromosomal deletions of the mutant Samd9l locus in their mouse model. ... Further, we observed nonrandom genetic deletion of the mutant Samd9l locus on mouse chromosome 6, mimicking chromosome 7 ... deletions observed in patients. Collectively, our study has enhanced our understanding of mutant Samd9l hematopoietic ...
Clonal deletion analysis of OPN promoter-luciferase constructs identified cis-regulatory regions. A specific promoter region, ...
Evidence for clonal deletion in tolerant kidney transplant patients. Sci Transl Med, 7 (272), 272ra10. http://dx.doi.org/ ... Savage TM, Shonts BA, Lau S, Obradovic A, Robins H, Shaked A, Shen Y, Sykes M (2020). Deletion of donor-reactive T cell clones ...
They include clonal deletion and the development of anergy in donor specific lymphocytes, development of suppressor lymphocytes ... Thymic or central tolerance mechanisms (clonal deletion) and peripheral tolerance mechanisms (eg, anergy) ensure that these ...
Immune B cell tolerance surveillance through clonal deletion anergy and receptor editing is also necessary to avoid ... Whether the same rules apply to autoimmune diseases involving clonal self-reactive T and B lymphocytes-a process referred to ... clonal selection theory). However their important role in adaptive immune responses is supported by the remarkable capacity of ...
It is in late metamorphosis that altered-self antigen-activated apopotsis (negative clonal deletion) is first observed and ...
Implications for the mechanisms underlying major histocompatibility complexrestricted antigen recognition and clonal deletion ...
Mesotheliomas show clonal cytogenetic aberrations (deletions of 1p, 3p, 22q are most common) - detected by fluorescence-in-situ ... Mesotheliomas show clonal cytogenetic aberrations (deletions of 1p, 3p, 22q are most common) - detected by fluorescence-in-situ ... Mesotheliomas show clonal cytogenetic aberrations (deletions of 1p, 3p, 22q most common) - detected by fluorescence-in-situ ... Mesotheliomas show clonal cytogenetic aberrations (deletions of 1p, 3p, 22q most common) - detected by fluorescence-in-situ ...
I. V beta-restricted clonal deletion of rat T cells differentiating in rat--,mouse chimeras. C D Surh,D P Gold,S Wiley,D B ...
... consistent with multiple deletion events (1-36 kb) occurring since clonal expansion of the clade. Most deletions shared a ... Deletions in the fljB locus that occurred subsequent to the initial clonal expansion of the epidemic clade accounted for the ... The clone from Spain is characterized by variable size deletions in the fljB locus, all distinct from deletions observed in the ... of clonal expansion of the epidemic clade. These include a complex pattern of deletions in the fljB locus and surrounding ...
A. Clonal Deletion. *The best-studied mechanism eliminating activated T-cell clones is activation-induced cell death (Figure 2) ... Mutations in Clonal Deletion Pathways. *Mice whose T-cells do not express Fas, display expanded lymphocyte populations in their ... MacFarlane Burnet pioneered the clonal selection theory: where host encounter with a foreign antigen selects for a particular ... He hypothesised that self-tolerance resulted from central deletion of forbidden clones, thereby eliminating potentially self- ...
Clonal Anergy G12.425.746.425.100 G12.535.425.100 Clonal Deletion G12.425.746.425.120 G12.535.425.120 Clonal Evolution G4.299. ... Gene Deletion G5.355.600.800.320 G5.558.800.320 Gene Duplication G5.355.600.320 G5.558.320 Gene Expression G5.355.310 G5.297 ... Sequence Deletion G5.355.600.800 G5.558.800 Sequence Inversion G5.355.600.805 G5.558.805 Serine-Arginine Splicing Factors ... Chromosome Deletion G5.355.600.800.180 G5.558.800.180 Chromosome Duplication G5.355.600.164 G5.558.164 Chromosome Inversion ...
... proceeds to clonal deletion, or selective removal of a subset of T cells that are directed against the donor graft. Without ... but in a subdued fashion so that the clonal deletion of the T cells is both more complete and long lasting. Therefore, it is ...
3D-F). When we evaluated clonal evolution of cells that were engineered to harbor the two separate deletions observed in ... G and H, Deletion 1 from patient V5300_b; I and J, deletion 2 from patient V5300_b; K and L, deletion 1 from patient V5301_b; ... G and H, Deletion 1 from patient V5300_b; I and J, deletion 2 from patient V5300_b; K and L, deletion 1 from patient V5301_b; ... to model one of the deletions in tumor V5300 and for which enzalutamide selection drove high clonal enrichment of deletion- ...
Today, Our main topic is development and clonal deletion of T lymphocytes. Well, Can this process be called as thymic education ...
Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH1. Mazor, Tali; Chesnelong, ... Loss of p16 expression is a sensitive marker of CDKN2A homozygous deletion in malignant meningiomas. Tang, Vivian; Lu, Rufei; ...
... clonal deletion).. Results are dose dependent. Higher doses lead to anergy or deletion, and low doses support suppression of ... Oral tolerance suggests a higher single dose will help not only with symptoms, but may affect anergy or clonal deletion. ...
Clonal deletion. *Tolerance in pregnancy. *Immunodeficiency. *Immune privilege. Immunogenetics. *Affinity maturation *Somatic ...
Clonal deletion (finding). Code System Preferred Concept Name. Clonal deletion (finding). Concept Status. Published. ...
Abortion, Clonal. Abortions, Clonal. Clonal Abortion. Clonal Abortions. Clonal Deletions. Deletion, Clonal. Deletions, Clonal. ... Clonal Deletions Deletion, Clonal Deletions, Clonal Clonal Abortion - Related but not broader or narrower Concept UI. M0026705 ... Clonal Deletion - Preferred Concept UI. M0026706. Scope note. Removal, via CELL DEATH, of immature lymphocytes that interact ... aborto clonal supresión clonal Scope note:. Eliminación, por MUERTE CELULAR, de linfocitos inmaduros que interactúan con ...
clonal deletion: A process by which contact with antigen (e.g., self antigen) at an early stage of lymphocyte differentiation ... negative selection: Deletion by apoptosis in the thymus of T-cells that recognize self peptides presented by self MHC ... clonal selection: The selection and activation by antigen of a lymphocyte bearing a complementary receptor, which then ...
Hilgemann, D. W., Lin, M. J., Fine, M., Frazier, G. & Wang, H. R., 2013, Sodium Calcium Exchange: A Growing Spectrum of Pathophysiological Implications: Proceedings of the 6th International Conference on Sodium Calcium Exchange. Springer Science and Business Media, LLC, p. 345-352 8 p. (Advances in Experimental Medicine and Biology; vol. 961).. Research output: Chapter in Book/Report/Conference proceeding › Conference contribution ...
They regulate self-reactive T cells by inducing anergy and clonal deletion and/or by expanding regulatory T cells (1). ... The results of deletion of individual cytokines, chemokines, and transcription factors have been catalogued in several recent ...
  • This is accomplished through a variety of means including CLONAL ANERGY and CLONAL DELETION. (uchicago.edu)
  • They regulate self-reactive T cells by inducing anergy and clonal deletion and/or by expanding regulatory T cells ( 1 ). (aai.org)
  • B7-CD28 co-stimulation modulates central tolerance via thymic clonal deletion and Treg generation through distinct mechanisms. (cocites.com)
  • Tolerance in TCR/cognate antigen double-transgenic mice mediated by incomplete thymic deletion and peripheral receptor downregulation. (ox.ac.uk)
  • These data demonstrate that T cells become tolerant to autologous and allogeneic HLA antigens expressed in the thymus via two different mechanisms: hematopoietic cells present in the thymus induce tolerance to "self"-antigens by clonal deletion, whereas thymic epithelial cells induce tolerance by clonal energy and possibly deletion of high affinity clones. (silverchair.com)
  • Large deletions influence the pathogenic potential of different clonal lineages within M. tuberculosis. (iimmun.ru)
  • Neutral microsatellite profiles of clinical samples collected between 1998 and 2001 revealed that the P. falciparum parasites in Peru consisted of at least five distinct clonal lineages. (cdc.gov)
  • These clonal lineages, designated as A, B, C, D and E, each displayed a distinct drug resistance and neutral microsatellite-based genetic profile 14 . (cdc.gov)
  • The cover image shows nonrandom chromosomal deletions of the mutant Samd9l locus in their mouse model. (jci.org)
  • 2002). The type of mutations observed in clonal cells obtained from CLL patients, primarily deletions of chromosomal material, require double strand breaks of the chromosomal DNA in order to occur (Dewald et al. (cdc.gov)
  • Chronic Myeloid Leukemia (CML) is a clonal hematological disease associated with a reciprocal chromosomal translocation between chromosomes 9 and 22, resulting in the Philadelphia (Ph) chromosome. (scielo.br)
  • If an underlying molecular or cytogenetic abnormality can be identified, the eosinophilia can be designated as a clonal disorder. (medscape.com)
  • Those in the MBC subtype harbored significantly more clonal CXCR4 mutations, deletion 13q, splenomegaly, and thrombocytopenia. (medjournal360.com)
  • Mutations in common clonal hematopoiesis driver genes were not found in the study population. (medscape.com)
  • Clonal hematopoiesis refers to clonal expansion of a subset of leukocytes carrying somatic mutations. (medscape.com)
  • The emergence of quinolone-resistant S. pneumoniae (QRSP) appears to be more dependent on fluoroquinolone selection of de novo spontaneous point mutations in the quinolone resistance-determining regions (QRDRs) of the topoisomerase genes gyrA and parC than on clonal dissemination (9-13). (cdc.gov)
  • The process occurs in different locations through clonal inactivation or clonal deletion. (ndnr.com)
  • Ig transgenic versions to neo-self Ags possess helped to classify two manifestations of B cell tolerance: clonal deletion and useful inactivation (anergy) (1C3). (healthanddietblog.info)
  • The mechanism that underlies this protection has, however, remained controversial, with clonal deletion, induction of suppressor cells or of type 2 immunity being implicated at one time or another. (mssm.edu)
  • Utilizing high depth sequencing and genotyping arrays, we comprehensively examined blood samples collected during the first week after birth for potential clonal hematopoiesis associated with fetal ZDV exposure, including clonal single nucleotide variants (SNVs), small insertions and deletions (indels), and large structural copy number or copy neutral alterations. (medscape.com)
  • Accumulations of TEs (TE islands) comprising 7.18% of the genome evolve faster than other regions with regard to single-nucleotide variants, gene/exon duplications and deletions and gene homology. (wurmlab.com)
  • The presence or absence of some of the amplified DNA fragments were observed in this study indicating homozygous deletions or insertions in the breast tumor DNA compared to the matched uninvolved tissue DNA. (cdc.gov)
  • Although the deletion of pfhrp2 in laboratory-adapted P. falciparum strains has previously been documented, this phenomenon had not been observed in natural P. falciparum populations until 2010 when P. falciparum isolates collected from the Peruvian Amazon were shown to be pfhrp2 -negative 5 6 7 . (cdc.gov)
  • Extensive characterization of four pfhrp2 -negative P. falciparum clinical isolates from Peru by whole genome microarray analysis revealed an approximately 20 kb deletion of the genome showing that the deletion is not restricted to pfhrp2 itself but extends to a number of neighboring genes 12 . (cdc.gov)
  • Moreover, tandem repeat sequences enabled the reconstruction of the isolates' largely clonal population structure and evolutionary history. (biomedcentral.com)
  • Isolates of serogroup A had the same antigenic formula (A:4:P1.9), the same variable regions VR1, VR2 and VR3, and belonged to the same clonal complex (CC5). (who.int)
  • The most frequent clonal complex in these isolates was CC35. (who.int)
  • In the process of clonal deletion , immature B cells that bind strongly to self-antigens expressed on tissues are signaled to commit suicide by apoptosis, removing them from the population. (edu.vn)
  • In vivo administration of staphylococcal enterotoxin B (SEB) to SCID-hu mice causes intrathymic clonal deletion of SEB-specific V beta(+) T cells that occurs already at the immature CD4(+)8(+) double positive stage. (unisr.it)
  • Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients. (columbia.edu)
  • These checkpoints also safeguard against autoimmunity by clonal deletion of autoreactive B cells that exhibit excessive BCR-signaling strength. (nature.com)
  • B cells are therefore selected for a narrow window of intermediate strength of BCR signaling, since both too weak (no functional BCR) and excessive strength (autoreactive BCR) of BCR signaling results in the clonal deletion and cell death. (nature.com)
  • But that practice, explains Dr. Starzl, eliminates the all-important, initial immune reaction against the donor organ, which under the right circumstances, proceeds to clonal deletion, or selective removal of a subset of T cells that are directed against the donor graft. (brightsurf.com)
  • What makes better sense, even though it may seem counterintuitive to most in the field, is to allow the immune activation against the donor organ to occur, but in a subdued fashion so that the clonal deletion of the T cells is both more complete and long lasting. (brightsurf.com)
  • A few CD8+ T cells, however, escape clonal deletion, and in the peripheral lymphoid organs of these mice, they exhibit low levels of the transgenic receptor and upregulated levels of the CD44 memory marker. (ox.ac.uk)
  • Lately, the difference between both of these has enter into issue as anergized cells have already been shown to have got a reduced life expectancy and may take circumstances of postponed deletion (4). (healthanddietblog.info)
  • Furthermore, the comparative contribution of deletion versus receptor Rabbit polyclonal to ZNF200 editing and enhancing to the reduction of autoreactive B cells has been reevaluated (5, 6). (healthanddietblog.info)
  • In the process of clonal anergy , however, B cells exposed to soluble antigen in the bone marrow are not physically deleted, but become unable to function. (edu.vn)
  • This clonal anergy can be completely reversed in vitro by stimulating the SEB-specific cells in the presence of exogenous IL-2 or by triggering of the CD28/CTLA-4 activation pathway. (unisr.it)
  • Collectively, these data demonstrate that in vivo administration of SEB to SCID-hu mice leads to activation, deletion, and anergy of SEB-specific human thymocytes and that the production of IL-2 and TNF-alpha is selectively switched off in these anergic T cells. (unisr.it)
  • The somatic mutation occurs initially in a single cell, which continues to grow and divide, producing a group of cells with the same mutation (a clonal population). (medlineplus.gov)
  • Any one of the events observed in this study could play an important role in the development of breast cancer or could occur during the clonal expansion of the genetically unstable breast cells. (cdc.gov)
  • PC subtypes harbored more deletion 6q, gain 6p, and had increased frequencies of IGHV3 genes, CD38 surface expression, and plasmacytic differentiation features. (medjournal360.com)
  • Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH1 . (bvsalud.org)
  • A remarkable amount of genotypic variation accumulated during clonal expansion that occurred during the epidemic, including multiple independent acquisitions of a novel prophage carrying the sopE gene and multiple deletion events affecting the phase II flagellin locus. (cdc.gov)
  • Analysis of the genomic deletions in the phase II flagellum locus responsible for the monophasic phenotype suggested that multiple independent clones may be emerging in the United States and Europe ( 9 ). (cdc.gov)
  • The most common genetic abnormality in PDGFRA -associated chronic eosinophilic leukemia results from a deletion of genetic material from chromosome 4 , which brings together part of the PDGFRA gene and part of the FIP1L1 gene, creating the FIP1L1-PDGFRA fusion gene. (medlineplus.gov)
  • Integrative genomic analysis in diffuse large B cell lymphoma (DLBCL) uncovered recurrent and highly focal deletions of 22q11.22, including the PRAME gene, which were associated with poor outcome. (bvsalud.org)
  • The objective of our study was to characterize the origin and possible reasons for the observed temporal and geographical expansion of pfhrp2 -negative P. falciparum parasites in the Peruvian Amazon, where the highest levels of deletions have been documented 7 . (cdc.gov)
  • The final B cell of interest is the memory B cell, which results from the clonal expansion of an activated B cell. (edu.vn)
  • Further, oxidant-induced toxicity in the normal population may facilitate the clonal expansion of the more resistant initiated cell during promotion 2,5,29 . (bvsalud.org)
  • These outcomes claim that T cell fitness instead of T cell clonal deletion or anergy is in charge of having less Fc-specific nTreg in KD individuals who develop CAA. (forgetmenotinitiative.org)
  • 15, 228S and 216S to investigate the nature of somatic changes and frequency with which clonal changes could be demonstrated during metastasis and progression. (edu.au)
  • Somatic changes were evident in approximately 70% of ovarian tumours, the most common being a deletion or reduction in intensity of a band suggesting loss of heterozygosity. (edu.au)
  • This study clearly demonstrates that DNA fingerprint analysis is a sensitive method to detect somatic changes in tumour DNA and for investigating the development of clonal heterogeneity in ovarian tumours. (edu.au)
  • These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times. (cdc.gov)
  • The P. falciparum parasite population structure in the Peruvian Amazon has previously been characterized as clonal 13 14 . (cdc.gov)
  • It was demonstrated that genomes of the related species of M. tuberculosis complex evolved through large unidirectional deletions leading to origin of M. tuberculosis sensu stricto, M. bovis and other species (M. canettii, M. microti, M. pinnipedii, M. caprae) from the same progenitor species. (iimmun.ru)
  • If reactive causes are ruled out and no underlying clonal origin is proven, the eosinophilia is described as idiopathic. (medscape.com)
  • Our study investigated clonal hematopoiesis in HIV-exposed uninfected (HEU) newborns, 94 of whom were ZDV-exposed and 91 antiretroviral therapy (ART)-unexposed and matched for potential confounding factors. (medscape.com)
  • Clonal deletion analysis of OPN promoter-luciferase constructs identified cis-regulatory regions. (duke.edu)
  • The first description of a monophasic Salmonella Typhimurium epidemic in Europe was that of a "Spanish clone," which emerged rapidly during 1997 and was characterized by a deletion in the allantoin-glyoxylate operon and the fljAB operon, phage type U302, and a heptaresistance pattern ACSuGSTSxT (resistant to ampicillin, chloramphenicol, sulfonamide, gentamicin, streptomycin, tetracycline, and co-trimoxazole) ( 10 ). (cdc.gov)
  • Primary eosinophilia is not a reactive phenomenon and can be described as either clonal or idiopathic in nature. (medscape.com)