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.
Lists of words, usually in alphabetical order, giving information about form, pronunciation, etymology, grammar, and meaning.
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.
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.
A member of the bcl-2 protein family that plays a role in the regulation of APOPTOSIS. Two major isoforms of the protein exist due to ALTERNATIVE SPLICING of the BCL2L1 mRNA and are referred to as Bcl-XS and Bcl-XL.
Membrane proteins encoded by the BCL-2 GENES and serving as potent inhibitors of cell death by APOPTOSIS. The proteins are found on mitochondrial, microsomal, and NUCLEAR MEMBRANE sites within many cell types. Overexpression of bcl-2 proteins, due to a translocation of the gene, is associated with follicular lymphoma.
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.
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.
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.
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.
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.
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.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
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.
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.
A loose confederation of computer communication networks around the world. The networks that make up the Internet are connected through several backbone networks. The Internet grew out of the US Government ARPAnet project and was designed to facilitate information exchange.
The portion of an interactive computer program that issues messages to and receives commands from a user.
Sequential operating programs and data which instruct the functioning of a digital computer.
The process of pictorial communication, between human and computers, in which the computer input and output have the form of charts, drawings, or other appropriate pictorial representation.
Software application for retrieving, presenting and traversing information resources on the World Wide Web.
Specific languages used to prepare computer programs.
Organized activities related to the storage, location, search, and retrieval of information.
Clonal hematopoietic stem cell disorders characterized by dysplasia in one or more hematopoietic cell lineages. They predominantly affect patients over 60, are considered preleukemic conditions, and have high probability of transformation into ACUTE MYELOID LEUKEMIA.
Anemia characterized by larger than normal erythrocytes, increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).
A severe sometimes chronic anemia, usually macrocytic in type, that does not respond to ordinary antianemic therapy.
Increased numbers of platelets in the peripheral blood. (Dorland, 27th ed)
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
The number of PLATELETS per unit volume in a sample of venous BLOOD.
Mapping of the KARYOTYPE of a cell.
An 11-kDa protein associated with the outer membrane of many cells including lymphocytes. It is the small subunit of the MHC class I molecule. Association with beta 2-microglobulin is generally required for the transport of class I heavy chains from the endoplasmic reticulum to the cell surface. Beta 2-microglobulin is present in small amounts in serum, csf, and urine of normal people, and to a much greater degree in the urine and plasma of patients with tubular proteinemia, renal failure, or kidney transplants.
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)
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.
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.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Large, transmembrane, non-covalently linked glycoproteins (alpha and beta). Both chains can be polymorphic although there is more structural variation in the beta chains. The class II antigens in humans are called HLA-D ANTIGENS and are coded by a gene on chromosome 6. In mice, two genes named IA and IE on chromosome 17 code for the H-2 antigens. The antigens are found on B-lymphocytes, macrophages, epidermal cells, and sperm and are thought to mediate the competence of and cellular cooperation in the immune response. The term IA antigens used to refer only to the proteins encoded by the IA genes in the mouse, but is now used as a generic term for any class II histocompatibility antigen.
A family of the suborder HAPLORHINI comprising only one genus, HYLOBATES (also called Nomascus or Symphalangus).
The branch of psychology concerned with similarities or differences in the behavior of different animal species or of different races or peoples.
A sucrose polymer of high molecular weight.
Lack of correspondence between the way a stimulus is commonly perceived and the way an individual perceives it under given conditions.
A person's view of himself.
The knowledge or perception that someone or something present has been previously encountered.
A form of anemia in which the bone marrow fails to produce adequate numbers of peripheral blood elements.
A piperidinyl isoindole originally introduced as a non-barbiturate hypnotic, but withdrawn from the market due to teratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppressive and anti-angiogenic activity. It inhibits release of TUMOR NECROSIS FACTOR-ALPHA from monocytes, and modulates other cytokine action.
Drug treatment designed to further diminish the disease toward complete remission following INDUCTION CHEMOTHERAPY. It helps to consolidate the gains during induction chemotherapy and may be followed by MAINTENANCE CHEMOTHERAPY.
Form of leukemia characterized by an uncontrolled proliferation of the myeloid lineage and their precursors (MYELOID PROGENITOR CELLS) in the bone marrow and other sites.
A reduction in the number of circulating ERYTHROCYTES or in the quantity of HEMOGLOBIN.
The use of two or more chemicals simultaneously or sequentially in the drug therapy of neoplasms. The drugs need not be in the same dosage form.

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?
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 ...
Update on Staphylococcal Superantigen-Induced Signaling Pathways and Therapeutic Interventions. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
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 and 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 Buret's clonal selection hypothesis. Burnet and Medawar won the Nobel Prize in 1960 for their ... Autoimmunity Immunology Peripheral tolerance Clonal selection Owen JA, Punt J, Stranford SA, Jones PP, Kuby J (2013). Kuby ...
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 ...
Antigen-specific mechanisms of peripheral tolerance include direct inactivation of effector T cells by either clonal deletion, ...
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 ...
Three hypotheses have gained widespread attention among immunologists: Clonal deletion theory, proposed by Burnet, according to ... 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 ...
... costimulation promotes maturation of regulatory T cell precursors and prevents their clonal deletion. „Front Immunol". 2, s. 30 ...
... may refer to in Immunology Clonal deletion, a process by which B cells and T cells are deactivated before act ... significantly upon specific antigens Clonal selection theory, a model for how the immune system responds to infection Clonal ... also called clonal anemone Vegetative cloning, a form of asexual reproduction in plants Clone (disambiguation) Clonalis House ... anergy, a lack of reaction by the body's defense mechanisms to foreign substance in Biology Clonal interference, a phenomenon ...
... 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 ... Clonal deletion is the removal through apoptosis of B cells and T cells that have expressed receptors for self before ...
... 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 ...
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 ... Clonal deletion is the removal through apoptosis of B cells and T cells that have expressed receptors for self before ...
Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH1.. Mazor T1, Chesnelong C2,3, ... Deletion or amplification of IDH1 was followed by clonal expansion and recurrence at a higher grade. Successful cultures ... Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH1 ... Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH1 ...
VßGene Family Usage in Spontaneous Lymphomas of AKR Mice: Evidence for Defective Clonal Deletion. Cees de Heer,1,2,3,4 Bernard ... The presence of V ß6+ lymphoma cells indicates that the lymphomagenesis is accompanied by a defective clonal deletion of cells ...
What is clonal deletion theory? Meaning of clonal deletion theory medical term. What does clonal deletion theory mean? ... Looking for online definition of clonal deletion theory in the Medical Dictionary? clonal deletion theory explanation free. ... clonal deletion theory. Also found in: Dictionary, Thesaurus, Legal, Encyclopedia. clo·nal de·le·tion the·o·ry. the elimination ... Clonal deletion theory , definition of clonal deletion theory by Medical dictionary https://medical-dictionary. ...
Here we identify mtDNA deletions as a driving force behind the premature aging phenotype of mitochondrial mutator mice, and ... DNA Deletions and Clonal Mutations Drive Premature Aging in Mitochondrial Mutator Mice Nat Genet. 2008 Apr;40(4):392-4. doi: ... Here we identify mtDNA deletions as a driving force behind the premature aging phenotype of mitochondrial mutator mice, and ... for a homology-directed DNA repair mechanism in mitochondria that is directly linked to the formation of mtDNA deletions. In ...
However, Bcl-xL was unable to block clonal deletion of thymocytes reactive with self-superantigens or H-Y antigen. These ... displays restricted distribution during T cell development and inhibits multiple forms of apoptosis but not clonal deletion in ... displays restricted distribution during T cell development and inhibits multiple forms of apoptosis but not clonal deletion in ...
Comment on "Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients" ... Comment on "Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients" ... Comment on "Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients" ... Comment on "Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients" ...
Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomide ... Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomide ... Unusual clonal evolution involving 5q in a case of myelodysplastic syndrome with deletion 5q 31 treated with lenalidomide ... 2006) Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 355:1456-65. ...
ERC Advanced Grant - Clonal deletion versus clonal diversion: Footprints of self-tolerance in the T-cell repertoire (Tolerance ... ERC Advanced Grant - Clonal deletion versus clonal diversion: Footprints of self-tolerance in the T-cell repertoire (Tolerance ... Moreover, the relative contribution of clonal deletion versus clonal diversion to tolerance at the level of diverse immune cell ... clonal deletion) or re-programmed to differentiate into regulatory T (Treg)-cells (clonal diversion). Paradoxically, both ...
Evidence for clonal deletion and anergy. E K Gao E K Gao ... Evidence for clonal deletion and anergy.. J Exp Med 1 April ... it is suggested that T cell contact with thymic epithelial cells induced clonal deletion of most of the host-reactive T cells ... deletion of V beta 11+ cells. Since marked tolerance was evident at the level of mature thymocytes, tolerance induction in the ... To account for the residual host reactivity of LN CD4+ cells and the incomplete deletion of V beta 11+ cells, ...
Antonyms for clonal deletion theory. 39 synonyms for theory: hypothesis, philosophy, system of ideas, plan, system, science, ... scheme, proposal, principles, ideology, thesis, belief, feeling.... What are synonyms for clonal deletion theory? ... Synonyms for clonal deletion theory in Free Thesaurus. ... Clonal deletion theory synonyms, clonal deletion theory ... clonal deletion theory provided by ,a style=color:#000 href=https://www.freethesaurus.com/clonal+deletion+theory, ...
... in which the predominant mechanism is clonal deletion of donor-specific T cells by donor hemopoietic cells in the recipient ... a low marrow dose generates tolerance with little evidence of clonal deletion. Only this low dose tolerance can be transferred ... We show here, for multiple minor Ag differences, that while a large inoculum of donor marrow produces significant deletion of ... Bone marrow transplantation induces either clonal deletion or infectious tolerance depending on the dose. ...
... Academic Article ... suggesting that clonal deletion of autoreactive cells was occurring in the pre-B-cell to B-cell transitional stage of B-cell ...
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Clonal%20deletion%20of%20potentially%20autoreactive%20T ... 20in%20mice&rft.date=1991&rft.au=Schneider,%20Reto&rft.genre=unknown&rft.btitle=Clonal%20deletion%20of%20potentially% ...
... ... κ B cells underwent clonal deletion. Their κ cells failed to populate lymph nodes, and the remaining splenic κ cells were ... The results suggest that deletion, not editing, is the major irreversible pathway of tolerance induction among peripheral B ...
Clonal deletion of immature CD4+8+ thymocytes in suspension culture by extrathymic antigen-presenting cells *Wojciech Swat ... Rights & permissionsfor article Clonal deletion of immature CD4,sup,+,/sup,8,sup,+,/sup, thymocytes in suspension culture by ... T-cell-specific deletion of T-cell receptor transgenes allows functional rearrangement of endogenous α- and β-genes *Horst ... Tolerance in T-cell-receptor transgenic mice involves deletion of nonmature CD4+8+ thymocytes *Pawel Kisielow ...
Clonal Deletion Theory of Immunity. Plant-based diets may be protective against multiple sclerosis because IGF-1 can prevent ... Clonal Selection Theory of Immunity. We may have a billion different types of antibody-releasing cells in our immune system, ...
Impaired peripheral clonal deletion in gp130F759/F759 mice. SEB (100 μg/mouse) was intraperitoneally injected into 6-wk-old ... Clonal Deletion In Vivo by Staphylococcal Enterotoxin B.. Staphylococcal enterotoxin B (SEB) (100 μg) (Toxin Technology) was ... Impairment of Thymic Negative Selection and Clonal Deletion in the Peripheral T Cells of gp130F759/F759 Mice In Vivo.. Both ... Then, we examined the effects of the Y759 mutation on the peripheral clonal deletion of activated T cells. For this study we ...
Recurrent deletions in clonal hematopoiesis are driven by microhomology-mediated end joining. ... The age-related clonal expansion of human hematopoietic stem and progenitor cells (HSPCs) is termed age-related clonal ... We detected the MH-based deletions in purified T-cells derived from all of these samples, suggesting that these deletions ... We identified a shared deletion signatures among the most common deletions in myeloid malignancies and provided evidence that ...
Clonal Deletion.png 1,440 × 816; 155 KB. *. Cluster of Differentiation mod.png 2,000 × 2,688; 245 KB. ...
Clonal Deletion.png 1.440×816; 155 kB. *. Cluster of Differentiation mod.png 2.000×2.688; 245 kB. ...
A rat cardiac allograft model (ACl to Lewis) was used to investigate the clonal deletion theory. Twelve groups of Lewis ... Pretransplant cytotoxic conditioning produces effects consistent with clonal deletion mechanisms. J Surg Res 1987 May;42(5):498 ... cyclosporine was required for the expression of this effect suggesting that clonal depression rather than clonal deletion had ...
Myelodysplastic syndrome with isolated 5q deletion (5q- syndrome). A clonal stem cell disorder characterized by defective ... Myelodysplastic syndrome with isolated 5q deletion (5q- syndrome). A clonal stem cell disorder characterized by defective ... reported a distinct hematologic disorder associated with acquired deletion of the long arm of chromosome 5 [del(5q)]. This ... reported a distinct hematologic disorder associated with acquired deletion of the long arm of chromosome 5 [del(5q)]. This ...
By introducing a deletion of the tyrosine motif into the germ line, and through homologous recombination in embryonic stem ... Clonal Deletion * Crosses, Genetic * Dendritic Cells / immunology * Endosomes / metabolism * Female * Galactosylceramides / ...
Clonal Deletion of Self-Reactive T Cells. Positive Selection Model of the Origin of MHC-Restricted T Cells. Molecular ... Clonal Abortion versus Clonal Anergy. Clonal Abortion and Clonal Anergy Come of Age in the Molecular Era. The Genesis of High- ... The Deletion-Anergy Decision. Consequences of Deletion versus Anergy. References. 3 Tolerant Autoreactive B Lymphocytes in the ... Deletion or Anergy?. Does the Follicular Mantle Zone Serve as a Reform School for Wayward B Cells?. References. Part III ...
Effect of lenalidomide treatment on clonal architecture of myelodysplastic syndromes without 5q deletion ... MDS patients ... Myelodysplastic syndromes with 5q deletion: pathophysiology and role of lenalidomide ... and decreased miR-145 and miR-146a ... on response to lenalidomide and the drug effects on clonal evolution remain unknown. We ... ...
Effect of lenalidomide treatment on clonal architecture of myelodysplastic syndromes without 5q deletion ... MDS patients ...
Intrathymic and extrathymic clonal deletion of T cells. Curr. Opin. Immunol. 7: 196 (1995).PubMedCrossRefGoogle Scholar ... Requirement of a second signal from antigen presenting cells in the clonal deletion of immature T cells. Internat. Immunol. 6: ... Cellular and peptide requirements for in vitro clonal deletion of immature thymocytes. Proc. Natl. Acad. Sci. USA 89: 9000 ( ... T cell tolerance by clonal elimination in the thymus. Cell 49: 273 (1987).PubMedCrossRefGoogle Scholar ...
Failing either will result in clonal deletion or anergy. 1/100 emerge immunocompetent ...
clonal selection of b-cells. - make antibodies > mess up but do not kill. - produce memory cells to remember invaders ... clonal deletion lymphocytes recognize bodys own cells and molecules that are weeded out by apoptosis ...
  • T lymphocytes can instead undergo clonal arrest, clonal anergy, and clonal editing. (wikipedia.org)
  • Evidence for clonal deletion and anergy. (rupress.org)
  • Deletion or Anergy? (elsevier.com)
  • Several mechanisms are involved in induction and maintenance of tolerance, including clonal deletion, clonal anergy, receptor editing, receptor down‐modulation and lymphocyte sequestration. (els.net)
  • Clonal anergy. (els.net)
  • See Clonal anergy, Deletion. (thefreedictionary.com)
  • To ensure its maintenance, a number of mechanisms exist, including the intrathymic deletion of autoreactive T cells ( 1 ), the induction of peripheral T cell anergy by self Ags ( 2 ), and clonal ignorance ( 3 ). (jimmunol.org)
  • In contrast to intrathymic clonal deletion, the silencing of autoreactive T cells through T cell anergy may be precarious, as a failure to maintain this nonresponsive state would result in dire consequences. (jimmunol.org)
  • If MHC/AG is presented to the autoreactive T-cell but is not followed by costimulation, the result is Clonal anergy. (bio.net)
  • Negative selection of autoreactive cells has been proposed to occur by clonal elimination or abortion (deletion), clonal silencing (anergy), and clonal alteration (receptor editing). (springer.com)
  • Self-directed lymphocytes may evade clonal deletion at ontogenesis but still remain harmless due to a mechanism called clonal anergy. (diva-portal.org)
  • T cells also have the opportunity to undergo clonal deletion within the thymic medulla if they express high affinity for self MHC/peptide complexes. (wikipedia.org)
  • Positive selection occurs in the thymic cortex, which suggests it is possible for a cell to undergo positive selection within the cortex and then negative selection in the medulla via clonal deletion. (wikipedia.org)
  • To account for the residual host reactivity of LN CD4+ cells and the incomplete deletion of V beta 11+ cells, it is suggested that T cell contact with thymic epithelial cells induced clonal deletion of most of the host-reactive T cells but spared a proportion of these cells (possibly low affinity cells). (rupress.org)
  • Before the disease onset, the T cells were hyperresponsive and thymic selection and peripheral clonal deletion were impaired. (rupress.org)
  • The results of this study challenge previous reports indicating that alloreactive T cell elimination and thymic clonal deletion are primary mediators of PTCy efficacy and provide strong evidence to support FoxP3+CD4+ Tregs as important effectors of PTCy benefits. (jci.org)
  • Interaction between self-antigen-loaded thymic stromal cells and newly generated T cells expressing self-reactive TCR specificities leads to the induction of central T cell tolerance via clonal deletion of self-reactive T cells. (frontiersin.org)
  • To our surprise, PPI-specific CD8 + T cells were already abundantly present in the nondiabetic pancreas, thus questioning the dogma that T1D is caused by defective thymic deletion or systemic immune dysregulation. (sciencemag.org)
  • Central control is effected in the thymus where there is irrecoverable deletion of autoreactive T cells that have high avidity for any of the array of self-proteins presented by thymic epithelium. (asnjournals.org)
  • Clonal deletion is the removal through apoptosis of B cells and T cells that have expressed receptors for self before developing into fully immunocompetent lymphocytes. (wikipedia.org)
  • It is important to note that not all lymphocytes expressing high affinity for self-antigen undergo clonal deletion. (wikipedia.org)
  • Complete clonal deletion results in apoptosis of all B and T lymphocytes expressing high affinity for self antigen. (wikipedia.org)
  • Incomplete clonal deletion results in apoptosis of most autoreactive B and T lymphocytes. (wikipedia.org)
  • Because most autoresponsive cells undergo clonal deletion, this allows microorganisms with epitopes similar to host antigen to escape recognition and detection by T and B lymphocytes. (wikipedia.org)
  • T lymphocytes specific for self‐peptides bound to major histocompatibility complex peptides are eliminated by clonal deletion, a process known as negative selection. (els.net)
  • Nemazee, D. A. and Burki, K. (1989) Clonal deletion of B lymphocytes in a transgenic mouse bearing anti-MHC class I antibody genes. (springer.com)
  • If autoreactive cells escape clonal deletion in either the thymus or the bone marrow, there are mechanisms in the periphery involving T regulatory cells to prevent the host from obtaining an autoimmune disease. (wikipedia.org)
  • T cells that show a high affinity for self MHC/peptide complexes can undergo clonal deletion in the thymus. (wikipedia.org)
  • The concept of immunologic tolerance arose from bone marrow transplantation in neonatal or irradiated mice, in which the predominant mechanism is clonal deletion of donor-specific T cells by donor hemopoietic cells in the recipient thymus. (ox.ac.uk)
  • T cell tolerance by clonal elimination in the thymus. (springer.com)
  • Clonal deletion and clonal diversion (Treg differentiation) are the major processes in the thymus that eliminate or control self-reactive T cells. (nih.gov)
  • The Thymus, site of clonal deletion, is very efficient in removing autoreactive T-cells. (bio.net)
  • In this context, we have shown that tumor antigen controlled by tissue-specific promoter is also expressed in the thymus to trigger clonal deletion ( 7 ). (aacrjournals.org)
  • 2006) Clonal deletion of thymocytes by circulating dendritic cells homing to the thymus. (els.net)
  • B cells bearing a low level of membrane immunoglobulin with the anti-H-2Kk idiotype were found in the bone marrows of H-2Kk recipients, suggesting that clonal deletion of autoreactive cells was occurring in the pre-B-cell to B-cell transitional stage of B-cell development. (scripps.edu)
  • However, for both B and T cells in the primary lymphoid organs, clonal deletion is the most common form of negative selection. (wikipedia.org)
  • B cells demonstrating high affinity for self cells can undergo clonal deletion within the bone marrow. (wikipedia.org)
  • Such T cells are often removed via clonal deletion, leaving autoreactive B cells unstimulated and unactivated. (wikipedia.org)
  • Epithelial cells are responsible for clonal deletion within the medulla. (wikipedia.org)
  • The presence of V ß 6 + lymphoma cells indicates that the lymphomagenesis is accompanied by a defective clonal deletion of cells expressing a possible autoreactive TCR. (hindawi.com)
  • Hybridization with EGRF1 specific probe (Abbott diagnostic, Rungis, France) located on 5q31, showed deletion in 75% of the cells. (haematologica.org)
  • Remarkably, T-cell tolerance operates via two fundamentally different mechanisms: potentially dangerous cells are either eliminated (clonal deletion) or re-programmed to differentiate into regulatory T (Treg)-cells (clonal diversion). (uni-muenchen.de)
  • The magnitude of this response was two- to fourfold less than the response of normal parental strain CD4+ cells and, in I-E(-)----I-E+ chimeras, was paralleled by approximately 70% deletion of V beta 11+ cells. (rupress.org)
  • We show here, for multiple minor Ag differences, that while a large inoculum of donor marrow produces significant deletion of Ag-reactive cells as expected, a low marrow dose generates tolerance with little evidence of clonal deletion. (ox.ac.uk)
  • 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. (scripps.edu)
  • The results suggest that deletion, not editing, is the major irreversible pathway of tolerance induction among peripheral B cells. (scripps.edu)
  • The age-related clonal expansion of human hematopoietic stem and progenitor cells (HSPCs) is termed age-related clonal hematopoiesis (ARCH) and is associated with the accumulation of recurrent somatic mutations. (nature.com)
  • To this end we used primary AML cells harboring MH-based deletions in ASXL1 and SRSF2 genes, together with myelofibrosis cells containing the CALR MH-based deletion. (nature.com)
  • We detected the MH-based deletions in purified T-cells derived from all of these samples, suggesting that these deletions originally occurred is multipotent hematopoietic stem cells (HSCs) capable of differentiating into both myeloid and lymphoid lineages. (nature.com)
  • This revealed that DSBs at specific genomic positions in ASXL1 and SRSF2 led to the formation of the MH-based deletions in these genes in K562 cells, recapitulating the mutational mechanisms naturally occurring in pre-leukemic HSCs. (nature.com)
  • DSB induction in LIG4 knockout K562 cells and in cells that were pre-treated with PARP1 inhibitors, provided evidence that the recurrent MH-based deletions are the result of PARP1 mediated and LIG4 independent repair. (nature.com)
  • Unexpectedly, POLQ knockout K562 cells successfully generated preL-MMEJ deletions in ASXL1 and SRSF2 in our CRISPR/Cas9 based system. (nature.com)
  • By introducing a deletion of the tyrosine motif into the germ line, and through homologous recombination in embryonic stem cells, we now describe knock-in mice with the CD1d cytoplasmic tail deleted. (nih.gov)
  • Intrathymic and extrathymic clonal deletion of T cells. (springer.com)
  • Low-concentrations of MTX achieve apoptosis and clonal deletion of activated peripheral T cells. (springer.com)
  • Immunosuppressive properties of methotrexate: apoptosis and clonal deletion of activated peripheral T cells. (springer.com)
  • Mature CD4 − CD8 − αβ + T cells (DNTC) in the periphery of TCR transgenic mice are resistant to clonal deletion in cognate Ag-expressing (Ag + ) mice. (jimmunol.org)
  • Unlike conventional cells, DNTC from TCR transgenic mice do not express endogenous TCRα genes ( 11 ), they develop independently of class I MHC molecules ( 12 , 13 ), and they are resistant to clonal deletion in cognate Ag-expressing mice ( 10 , 12 ). (jimmunol.org)
  • Cells that react with the body's own proteins are eliminated by a process known as "clonal deletion. (encyclopedia.com)
  • The process of clonal deletion ensures that the mature T cells, which circulate in the blood, will not interact with or destroy an individual's own tissues and organs. (encyclopedia.com)
  • This process of clonal proliferation ensures that enough cells are produced to mount a successful immune response. (encyclopedia.com)
  • 5. A method of reducing the severity of a T cell proliferative disease mediated by unregulated T cell clonal replication of T cells having restricted T cell receptor heterogeneity in a mammal, comprising administering the composition of claim 1. (google.com)
  • In addition to clonal deletion, CD4 + CD25 + regulatory T (Treg) cells play a pivotal role in the maintenance of peripheral self-tolerance ( 8 - 12 ). (aacrjournals.org)
  • Rather than present a comprehensive review of the findings in this area, the authors will concentrate on the role of clonal deletion in the tolerization of immature B-cells. (springer.com)
  • Plays a role in antigen receptor signaling for both clonal expansion and deletion in lymphoid cells. (uniprot.org)
  • Myelodysplastic syndrome (MDS) in childhood encompasses a diverse group of bone marrow disorders that share a common clonal defect of stem cells and that result in ineffective hematopoiesis with dysplastic changes in the marrow. (medscape.com)
  • Clonal Deletion theory , proposed by Burnet , according to which self-reactive lymphoid cells are destroyed during the development of the immune system in an individual. (wikipedia.org)
  • Genomic instability may play an essential role in leukemogenesis by promoting the accumulation of genetic lesions responsible for clonal evolution. (mdpi.com)
  • However, Bcl-xL was unable to block clonal deletion of thymocytes reactive with self-superantigens or H-Y antigen. (rupress.org)
  • Although the tremendous clonal diversity expressed in the B-cell receptor (BCR) repertoire is beneficial for mounting immune responses to foreign antigens, it is simultaneously detrimental in that it may include a multitude of BCRs capable of recognizing self antigens. (springer.com)
  • Here we identify mtDNA deletions as a driving force behind the premature aging phenotype of mitochondrial mutator mice, and provide evidence for a homology-directed DNA repair mechanism in mitochondria that is directly linked to the formation of mtDNA deletions. (nih.gov)
  • Bcl-XL displays restricted distribution during T cell development and inhibits multiple forms of apoptosis but not clonal deletion in transgenic mice. (rupress.org)
  • In summary, whereas mitochondrial base substitution and deletions previously have been shown to correlate with premature and natural aging, respectively, we show that a high level of apyrimidinic sites lead to mitochondrial DNA cytotoxicity, which causes apoptosis, followed by neurodegeneration. (asm.org)
  • Pretransplant cytotoxic conditioning produces effects consistent with clonal deletion mechanisms. (mcw.edu)
  • Immunological tolerance and mechanisms of T cell clonal deletion. (utwente.nl)
  • 2) Attempting to understand mechanisms and factors effecting clonal expansion of mitochondrial DNA mutations. (ncl.ac.uk)
  • The best characterized mechanism of self-tolerance is clonal deletion ( 5 , 6 ). (aacrjournals.org)
  • My fellowship aims to understand how mitochondrial DNA deletions clonally expand with age and disease, with a focus on the impact of skeletal muscle biology. (ncl.ac.uk)
  • Therefore, incomplete clonal deletion allows for a balance between the host's ability to recognize foreign antigens and self antigens. (wikipedia.org)
  • Nossal, G. J. V. and Pike, B. L. (1975) Evidence for the clonal abortion theory of B-lymphocyte tolerance. (springer.com)
  • 3 We report a patient with the 5q- syndrome , who had resistance to lenalidomide treatment, associated to emergence of clonal evolution involving chromosome. (haematologica.org)
  • A clonal chromosome deletion 2p21 was found in endomyometriosis by Verhest et al. (wikipedia.org)
  • A unique clonal chromosome 2 deletion in endomyometriosis. (wikipedia.org)
  • Monosomy 7 is most often associated with juvenile myelomonocytic leukemia (JMML), and as many as 30% of children with JMML have a deletion of all or part of chromosome 7. (medscape.com)
  • Myelodysplastic syndrome with isolated 5q deletion (5q- syndrome). (unipv.it)
  • Our patient showed no erythroid response to lenalidomide and clonal cytogenetic evolution that was unusual in the 5q- syndrome . (haematologica.org)
  • Deletion (21)(q21.2q22.12) as a sole clonal cytogenetic abnormality in a lobular capillary hemangioma of the nasal cavity. (medscape.com)
  • A clonal stem cell disorder characterized by defective ribosome biogenesis. (unipv.it)
  • Bone marrow transplantation induces either clonal deletion or infectious tolerance depending on the dose. (ox.ac.uk)
  • Thus, clonal deletion can help protect individuals against autoimmunity. (wikipedia.org)
  • If they demonstrate high affinity for self-antigen, one method of preventing autoimmunity is through clonal deletion. (wikipedia.org)
  • Moreover, the relative contribution of clonal deletion versus clonal diversion to tolerance at the level of diverse immune cell repertoires has not been determined. (uni-muenchen.de)
  • The main objectives are (i) to identify and classify deleted or diverted TCR-entities through comparing 'uncensored' and 'censored' repertoires in the absence or presence of a disease-relevant autoantigen and (ii) to identify TCR intrinsic features as well as T-cell extrinsic determinants that specify clonal deletion versus clonal diversion. (uni-muenchen.de)
  • Differential TCR signaling in clonal deletion and clonal diversion. (nih.gov)
  • Clonal expansion and epigenetic reprogramming following deletion or amplification of mutant IDH1. (nih.gov)
  • Deletion or amplification of IDH1 was followed by clonal expansion and recurrence at a higher grade. (nih.gov)
  • Rajewsky, K. (1996) Clonal selection and learning in the antibody system. (springer.com)
  • Burnet, F.M. (1959) Clonal Selection Theory of Acquired Immunity Vanderbilt University, Nashville, TN. (springer.com)
  • Our goal is to understand the full evolutionary history of human brain tumors, from the first mutation and epimutation through clonal selection and tumor recurrence. (ucsf.edu)
  • In the current work, we aimed to identify recurrent deletion signatures in myeloid malignancies and to study the mutagenic processes promoting them. (nature.com)
  • We used additional methods to validate these results, and concluded that recurrent MH-based deletions originate in early HSCs and therefore are pre-leukemic and part of clonal hematopoiesis. (nature.com)
  • We therefore used our K562 based model system to study the repair machinery involved in the formation of the recurrent MH-based deletions. (nature.com)
  • Recurrent KBTBD4 small in-frame insertions and absence of DROSHA deletion or DICER1 mutation differentiate pineal parenchymal tumor of intermediate differentiation (PPTID) from pineoblastoma. (ucsf.edu)
  • Based on cohorts of patients, we mapped the microdeletions breakpoints and developed a breakpoint-specific fluorescent multiplex PCR which allows detection of recurrent intragenic deletions. (biomedsearch.com)
  • Loss of 10q25.2-qter arises in a longitudinal manner in paired recurrent tumor specimens, whereas the prognostically favorable 1p/19q co-deletion is the only CNA that is stable across spatial regions and recurrent tumors. (biomedcentral.com)
  • Inspecting the genomic sequences around the most common somatic deletions, we identified a common signature for the three most common deletions in myeloid malignancies which occur in CALR , ASXL1 and SRSF2 genes. (nature.com)
  • Vκ genes rearrange by inversion or deletion. (els.net)
  • As we were aiming to characterize the biological processes driving these deletions, we first aimed to identify the cell of origin in which they occur. (nature.com)
  • Negative selection via clonal deletion can also occur in the cortex, but occurs frequently in the medulla. (nih.gov)
  • High-affinity self-reactive clones can die via clonal deletion, and the threshold between positive and negative selection is hypothesized to be steep. (nih.gov)
  • Some Tregs may have very highly self-reactive TCRs and are rescued from deletion via cytokine signaling or by virtue of having a second TCR (dotted line). (nih.gov)
  • Which target cell populations are sensitive to deletion? (springer.com)
  • Is clonal deletion necessary for the maintenance of B-cell tolerance? (springer.com)
  • If such a cell acquires additional genetic alterations providing a clonal advantage, this may lead to malignant transformation and ultimately to cancer [ 1 ]. (mdpi.com)
  • Breakpoint-specific multiplex PCR allows the detection of IKZF1 intragenic deletions and minimal residual disease monitoring in B-cell precursor acute lymphoblastic leukemia. (biomedsearch.com)
  • This is called Clonal Ignorance. (bio.net)
  • Clonal and subclonal mutations of NOTCH1 and TP53 , clonal mutations of SF3B1 , and ATM mutations in CLL have an impact on clinical outcome. (bloodjournal.org)
  • We identified a high proportion of subclonal mutations, isolated or associated with clonal aberrations. (bloodjournal.org)
  • Indeed, disease progression is often driven by clonal evolution into complex karyotypes. (mdpi.com)
  • As we suspected that MH-based deletions might be the result of mutagenic double strand break (DSB) repair in early HSCs, we aimed to model DSB repair around CALR , ASXL1 and SRSF2 hotspot by using the CRISPR/Cas9 system. (nature.com)
  • This signature involves the joining of two pre-existing identical sequences flanking the deletions. (nature.com)
  • Deletion or amplification of mutant IDH1 during malignant progression. (nih.gov)
  • Clonal deletion is thought to be the most common type of negative selection. (wikipedia.org)
  • Most of these undergo negative selection by clonal deletion. (wikipedia.org)
  • Once a primary rearrangement has been obtained, a secondary rearrangement may also use either deletion or inversion, depending on the orientation of the Vκ involved. (els.net)
  • A rat cardiac allograft model (ACl to Lewis) was used to investigate the clonal deletion theory. (mcw.edu)
  • Genomic studies have revealed the complex clonal heterogeneity of chronic lymphocytic leukemia (CLL). (bloodjournal.org)