4-1BB Ligand: A membrane bound member of the TNF superfamily that is expressed on activated B-LYMPHOCYTES; MACROPHAGES; and DENDRITIC CELLS. The ligand is specific for the 4-1BB RECEPTOR and may play a role in inducing the proliferation of activated peripheral blood T-LYMPHOCYTES.T-Lymphocytes: Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.Antigens, CD137: A member of the tumor necrosis factor receptor superfamily that is specific for 4-1BB LIGAND. It is found in a variety of immune cell types including activated T-LYMPHOCYTES; NATURAL KILLER CELLS; and DENDRITIC CELLS. Activation of the receptor on T-LYMPHOCYTES plays a role in their expansion, production of cytokines and survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Dendritic Cells: Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION).Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)B-Lymphocytes: 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.Tumor Necrosis Factors: A family of proteins that were originally identified by their ability to cause NECROSIS of NEOPLASMS. Their necrotic effect on cells is mediated through TUMOR NECROSIS FACTOR RECEPTORS which induce APOPTOSIS.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Receptors, Nerve Growth Factor: Cell surface receptors that bind NERVE GROWTH FACTOR; (NGF) and a NGF-related family of neurotrophic factors that includes neurotrophins, BRAIN-DERIVED NEUROTROPHIC FACTOR and CILIARY NEUROTROPHIC FACTOR.Tumor Necrosis Factor Ligand Superfamily Member 14: A member of tumor necrosis factor superfamily found on activated LYMPHOCYTES and MONOCYTES. It occurs as transmembrane protein that can be cleaved to release a secreted form that specifically binds to LYMPHOTOXIN BETA RECEPTOR and TUMOR NECROSIS FACTOR RECEPTOR SUPERFAMILY, MEMBER 14.Search Engine: Software used to locate data or information stored in machine-readable form locally or at a distance such as an INTERNET site.Databases, Genetic: Databases devoted to knowledge about specific genes and gene products.Tumor Necrosis Factor Ligand Superfamily Member 15: A member of tumor necrosis factor superfamily found on ENDOTHELIAL CELLS that plays a role in the inhibition of endothelial cell growth and PHYSIOLOGIC ANGIOGENESIS.Genome, Human: The complete genetic complement contained in the DNA of a set of CHROMOSOMES in a HUMAN. The length of the human genome is about 3 billion base pairs.OX40 Ligand: A membrane-bound tumor necrosis family member that is expressed on activated antigen-presenting cells such as B-LYMPHOCYTES and MACROPHAGES. It signals T-LYMPHOCYTES by binding the OX40 RECEPTOR.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Internet: 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.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Molecular Sequence Data: 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.Amino Acid Sequence: 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.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Cloning, Molecular: 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.Escherichia coli: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Research: Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. (Webster, 3d ed)Genetic Vectors: DNA molecules capable of autonomous replication within a host cell and into which other DNA sequences can be inserted and thus amplified. Many are derived from PLASMIDS; BACTERIOPHAGES; or VIRUSES. They are used for transporting foreign genes into recipient cells. Genetic vectors possess a functional replicator site and contain GENETIC MARKERS to facilitate their selective recognition.Baculoviridae: Family of INSECT VIRUSES containing two subfamilies: Eubaculovirinae (occluded baculoviruses) and Nudibaculovirinae (nonoccluded baculoviruses). The Eubaculovirinae, which contain polyhedron-shaped inclusion bodies, have two genera: NUCLEOPOLYHEDROVIRUS and GRANULOVIRUS. Baculovirus vectors are used for expression of foreign genes in insects.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.BooksPublishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing.MEDLINE: The premier bibliographic database of the NATIONAL LIBRARY OF MEDICINE. MEDLINE® (MEDLARS Online) is the primary subset of PUBMED and can be searched on NLM's Web site in PubMed or the NLM Gateway. MEDLINE references are indexed with MEDICAL SUBJECT HEADINGS (MeSH).Serial Publications: Publications in any medium issued in successive parts bearing numerical or chronological designations and intended to be continued indefinitely. (ALA Glossary of Library and Information Science, 1983, p203)Biological Science Disciplines: All of the divisions of the natural sciences dealing with the various aspects of the phenomena of life and vital processes. The concept includes anatomy and physiology, biochemistry and biophysics, and the biology of animals, plants, and microorganisms. It should be differentiated from BIOLOGY, one of its subdivisions, concerned specifically with the origin and life processes of living organisms.Abstracting and Indexing as Topic: Activities performed to identify concepts and aspects of published information and research reports.Information Storage and Retrieval: Organized activities related to the storage, location, search, and retrieval of information.Bibliometrics: The use of statistical methods in the analysis of a body of literature to reveal the historical development of subject fields and patterns of authorship, publication, and use. Formerly called statistical bibliography. (from The ALA Glossary of Library and Information Science, 1983)Fetal Blood: Blood of the fetus. Exchange of nutrients and waste between the fetal and maternal blood occurs via the PLACENTA. The cord blood is blood contained in the umbilical vessels (UMBILICAL CORD) at the time of delivery.Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.Hypersensitivity, Immediate: Hypersensitivity reactions which occur within minutes of exposure to challenging antigen due to the release of histamine which follows the antigen-antibody reaction and causes smooth muscle contraction and increased vascular permeability.Infant, Newborn: An infant during the first month after birth.Th2 Cells: Subset of helper-inducer T-lymphocytes which synthesize and secrete the interleukins IL-4, IL-5, IL-6, and IL-10. These cytokines influence B-cell development and antibody production as well as augmenting humoral responses.Th1 Cells: Subset of helper-inducer T-lymphocytes which synthesize and secrete interleukin-2, gamma-interferon, and interleukin-12. Due to their ability to kill antigen-presenting cells and their lymphokine-mediated effector activity, Th1 cells are associated with vigorous delayed-type hypersensitivity reactions.Asthma: A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).Clone Cells: 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)Lymphocyte Activation: Morphologic alteration of small B LYMPHOCYTES or T LYMPHOCYTES in culture into large blast-like cells able to synthesize DNA and RNA and to divide mitotically. It is induced by INTERLEUKINS; MITOGENS such as PHYTOHEMAGGLUTININS, and by specific ANTIGENS. It may also occur in vivo as in GRAFT REJECTION.
(1/160) 4-1BBL cooperates with B7-1 and B7-2 in converting a B cell lymphoma cell line into a long-lasting antitumor vaccine.

A20 is a B cell lymphoma that constitutively expresses the costimulatory molecule B7-2 yet grows readily as a tumor in syngeneic BALB/c mice. We have compared the tumorigenicity of A20 variants expressing either B7-1 (A20/B7-1) or B7-2 (A20/B7-2) with an A20 variant expressing B7-1 and B7-2 with 4-1BBL (A20/4-1BBL), a costimulatory member of the TNF family. Mice injected with tumors expressing the vector backbone (A20/CMV) or B7-1 developed tumors within 25 days of s.c. injection. In contrast, mice injected with A20/4-1BBL were tumor free for the 150-day follow-up period, while 25% of mice injected with A20/B7-2 developed tumors. Tumorigenicity experiments using nude mice indicated the requirement for T cells for variant rejection. Almost all mice that resisted the initial tumor challenge were resistant to further challenge with the parental tumor. Splenocytes from these mice showed high CTL lytic activity against the parental tumor, A20, as well as the syngeneic BALB/c lymphoma K46J, but showed background levels of lytic activity against the congenic SCID thymoma line ST-D2 or the allogeneic EL4 thymoma. In vitro blocking experiments with anti-B7-1 plus anti-B7-2 and/or soluble 4-1BB receptor showed B7-1, B7-2, and 4-1BBL all contributed to the CTL activity. Thus, the data show that neither B7-1 or B7-2 alone can confer full immunogenicity to the A20 lymphoma but that the addition of 4-1BBL results in a tumor that is highly immunogenic and can confer long-lasting protection against challenge with parental tumor in vivo.  (+info)

(2/160) Cutting edge: 4-1BB is a bona fide CD8 T cell survival signal.

After recognition of Ag/MHC and ligation of a costimulatory molecule, resting T cells will clonally expand and then delete to very low levels. Previously, it was shown that deletion can be prevented by coinjection of cytokines or proinflammatory agents such as adjuvants. Here, we demonstrate that ligation of 4-1BB blocks deletion of superantigen-activated T cells in the absence of adjuvant or additional cytokine treatment. Nearly 10 times as many staphylococcal enterotoxin A-specific T cells were detected in the spleens of mice injected 21 days previously with staphylococcal enterotoxin A and an agonist anti-4-1BB Ab compared with mice given staphylococcal enterotoxin A and a control IgG. Even though both CD4- and CD8-activated T cells expressed 4-1BB, a higher proportion of CD8 T cells were rescued compared CD4 T cells. These data suggest that although 4-1BB provides costimulation, it may also promote long-term T cell survival.  (+info)

(3/160) Analysis of 4-1BB ligand (4-1BBL)-deficient mice and of mice lacking both 4-1BBL and CD28 reveals a role for 4-1BBL in skin allograft rejection and in the cytotoxic T cell response to influenza virus.

4-1BB ligand (4-1BBL) is a member of the TNF family expressed on activated APC. 4-1BBL binds to 4-1BB (CD137) on activated CD4 and CD8 T cells and in conjunction with strong signals through the TCR provides a CD28-independent costimulatory signal leading to high level IL-2 production by primary resting T cells. Here we report the immunological characterization of mice lacking 4-1BBL and of mice lacking both 4-1BBL and CD28. 4-1BBL-/- mice mount neutralizing IgM and IgG responses to vesicular stomatitis virus that are indistinguishable from those of wild-type mice. 4-1BBL-/- mice show unimpaired CTL responses to lymphocytic choriomeningitis virus (LCMV) and exhibit normal skin allograft rejection but have a weaker CTL response to influenza virus than wild-type mice. 4-1BBL-/-CD28-/- mice retain the CTL response to LCMV, respond poorly to influenza virus, and exhibit a delay in skin allograft rejection. In agreement with these in vivo results, allogeneic CTL responses of CD28-/- but not CD28+/+ T cells to 4-1BBL-expressing APC are substantially inhibited by soluble 4-1BB receptor as is the in vitro secondary response of CD28+ T cells to influenza virus peptides. TCR-transgenic CD28-/- LCMV glycoprotein-specific T cells are insensitive to the presence of 4-1BBL when a wild-type peptide is used, but the response to a weak agonist peptide is greatly augmented by the presence of 4-1BBL. These results further substantiate the idea that different immune responses vary in their dependence on costimulation and suggest a role for 4-1BBL in augmenting suboptimal CTL responses in vivo.  (+info)

(4/160) 4-1BB ligand, a member of the TNF family, is important for the generation of antiviral CD8 T cell responses.

4-1BB (CD137) is a costimulatory molecule expressed on activated T cells and interacts with 4-1BB ligand (4-1BBL) on APCs. To investigate the role of 4-1BB costimulation for the development of primary immune responses, 4-1BBL-deficient (4-1BBL-/-) mice were infected with lymphocytic choriomeningitis virus (LCMV). 4-1BBL-/- mice were able to generate CTL and eliminate acute LCMV infection with normal kinetics, but CD8 T cell expansion was 2- to 3-fold lower than in wild-type (+/+) mice. In the same mice, virus-specific CD4 Th and B cell responses were minimally affected, indicating that 4-1BB costimulation preferentially affects CD8 T cell responses. This result contrasts with our earlier work with CD40L-deficient (CD40L-/-) mice, in which the CD8 T cell response was unaffected and the CD4 T cell response was markedly impaired. When both 4-1BBL- and B7-dependent signals were absent, CD8 T cell expansion was further reduced, resulting in lower CTL activity and impairing their ability to clear LCMV. Altogether, these results indicate that T cells have distinct costimulatory requirements: optimal CD8 responses require 4-1BBL-dependent interactions, whereas CD4 responses are minimally affected by 4-1BB costimulation, but require CD40-CD40L and B7-dependent interactions.  (+info)

(5/160) Critical contribution of OX40 ligand to T helper cell type 2 differentiation in experimental leishmaniasis.

Infection of inbred mouse strains with Leishmania major is a well characterized model for analysis of T helper (Th)1 and Th2 cell development in vivo. In this study, to address the role of costimulatory molecules CD27, CD30, 4-1BB, and OX40, which belong to the tumor necrosis factor receptor superfamily, in the development of Th1 and Th2 cells in vivo, we administered monoclonal antibody (mAb) against their ligands, CD70, CD30 ligand (L), 4-1BBL, and OX40L, to mice infected with L. major. Whereas anti-CD70, anti-CD30L, and anti-4-1BBL mAb exhibited no effect in either susceptible BALB/c or resistant C57BL/6 mice, the administration of anti-OX40L mAb abrogated progressive disease in BALB/c mice. Flow cytometric analysis indicated that OX40 was expressed on CD4(+) T cells and OX40L was expressed on CD11c(+) dendritic cells in the popliteal lymph nodes of L. major-infected BALB/c mice. In vitro stimulation of these CD4(+) T cells showed that anti-OX40L mAb treatment resulted in substantially reduced production of Th2 cytokines. Moreover, this change in cytokine levels was associated with reduced levels of anti-L. major immunoglobulin (Ig)G1 and serum IgE. These results indicate that anti-OX40L mAb abrogated progressive leishmaniasis in BALB/c mice by suppressing the development of Th2 responses, substantiating a critical role of OX40-OX40L interaction in Th2 development in vivo.  (+info)

(6/160) Immunomodulatory gene therapy with interleukin 12 and 4-1BB ligand: long- term remission of liver metastases in a mouse model.

BACKGROUND: The success of immunomodulatory cancer therapy is frequently hampered by the transient nature of the antitumor immune response. We have shown previously in a mouse model that interleukin 12 (IL-12) generates a strong natural killer (NK) cell-mediated antitumor response and reduces liver metastases induced by a colon carcinoma cell line. However, only a small percentage of the treated animals developed the cytotoxic T-lymphocytic response required for a long-term systemic antitumor immunity. 4-1BB is a co-stimulatory molecule expressed on the surface of activated T cells. Interaction of 4-1BB with its natural ligand (4-1BBL) has been shown to amplify T-cell (especially CD8+)-mediated immunity. In this study, we investigated the effects of adenovirus-mediated gene therapy delivering both IL-12 and 4-1BBL genes on mice with hepatic metastases induced by colon cancer cells. METHODS: Syngeneic BALB/c mice received intrahepatic injection of poorly immunogenic MCA26 colon cancer cells. Various combinations of replication-defective adenoviruses expressing IL-12 and 4-1BBL genes were injected into the established liver tumors. Changes in tumor size and animal survival were then monitored. All statistical tests were two-sided. RESULTS: The long-term survival rate of mice treated with the combination of IL-12 and 4-1BBL was significantly improved over that of animals in the control group (P =.0001). In vivo depletion of NK cells or CD8+ T cells completely abolished the long-term survival advantage of the IL-12 plus 4-1BBL-treated animals (P<.002). Moreover, the systemic immunity induced by this combination treatment protected these animals against a subcutaneous challenge with parental MCA26 cells. CONCLUSION: Adenovirus-mediated transfer of IL-12 and 4-1BBL genes directly into liver tumors resulted in tumor regression that required both NK and CD8+ T cells and generated a potent, long-lasting antitumor immunity.  (+info)

(7/160) 4-1BB: still in the midst of darkness.

4-1BB is a member of the tumor necrosis factor receptor superfamily. The receptor functions mainly as a costimulatory molecule in T lymphocytes. In addition, several lines of evidence have shown that interactions between 4-1BB and its ligand are involved in the antigen presentation process and the generation of cytotoxic T cells. Recent studies, however, have demonstrated that 4-1BB plays more diverse roles: Signals through 4-1BB are important for long-term survival of CD8+ T cells and the induction of helper T cell anergy. Clinically, there is great interest in 4-1BB, because T-cell activation induced by anti-4-1BB monoclonal antibodies is highly efficient in the eradication of established tumor cells in mice. Now, since mice deficient in 4-1BB or the 4-1BB ligand are available, subtle roles played by 4-1BB may be revealed in the near future.  (+info)

(8/160) Rejection of disseminated metastases of colon carcinoma by synergism of IL-12 gene therapy and 4-1BB costimulation.

In an orthotopic model of metastatic colon carcinoma established in the liver of mice, we have previously shown that the natural killer (NK) cells were the major effectors after intratumoral delivery of a recombinant adenovirus expressing the murine IL-12 gene. However, tumor cure and long-term survival were achieved only in a minority of animals. In the present study, we generated an effective antitumoral CD8(+ ) T-cell response by the combination of IL-12 gene therapy and systemic delivery of an agonistic monoclonal antibody against 4-1BB, a costimulatory molecule expressed on activated T cells. In the IL-12 plus anti-4-1BB combination treatment, the effective dose of IL-12 could even be reduced even up to 18-fold and still achieved a better efficacy than the maximal dose of either treatment alone. We further demonstrate that the innate and the adaptive antitumoral immune responses were synergistic, as animals bearing hepatic as well as multiple pulmonary metastases were quantitatively cured of their diseases after IL-12 gene therapy + anti-4-1BB combination treatment. Both NK and CD8(+) T cells were necessary in maintaining the long-term antitumor immunity, as depletion of either cell type in the cured animals abolished their abilities to reject tumor cells implanted at distal sites. These results indicate that synergism between innate and adaptive immune responses may be effectively exploited to treat patients with metastatic diseases.  (+info)

*  4-1BB ligand
4-1BBL (4-1BB ligand) is found on APCs (antigen presenting cells) and binds to 4-1BB. CD137L Lotze, Michael (2001). Dendritic ... 4-1BB is a type 2 transmembrane glycoprotein receptor belonging to the TNF superfamily, expressed on activated T Lymphocytes. ... ISBN 0-12-455851-8. 4-1BB Ligand at the US National Library of Medicine Medical Subject Headings (MeSH). ...
*  CD137
Schwarz H (2005). "Biological activities of reverse signal transduction through CD137 ligand". J. Leukoc. Biol. 77 (3): 281-6. ... receptor and ligand and potential applications in cancer therapy". Arch. Immunol. Ther. Exp. (Warsz.). 47 (5): 275-9. PMID ... Zhou Z, Kim S, Hurtado J, Lee ZH, Kim KK, Pollok KE, Kwon BS (1995). "Characterization of human homologue of 4-1BB and its ... ligand". Immunol. Lett. 45 (1-2): 67-73. doi:10.1016/0165-2478(94)00227-I. PMID 7622190. Alderson MR, Smith CA, Tough TW, Davis ...
*  CPC Scientific
"Costimulation as a platform for the development of vaccines: a peptide-based vaccine containing a novel form of 4-1BB ligand ...
*  B7 (protein)
CD28 and CTLA-4 each interact with both B7-1 and B7-2. There are several steps to activation of the immune system against a ... Binding of the B7 of APC to CTLA-4 of T-cells causes inhibition of the activity of T-cells. There are two major types of B7 ... In the TNF family of molecules, the protein 4-1BB (CD137) on the T cell may bind to 4-1BB ligand (4-1BBL) on the APC. The B7 ( ... CTLA-4-knockout mice are unable to stop immune responses, and develop a fatal massive lymphocyte proliferation. Apart from B7-1 ...
*  Immune checkpoint
Its ligand is ICOSL, expressed mainly on B cells and dendritic cells. The molecule seems to be important in T cell effector ... The ligand for GITR is mainly expressed on antigen presenting cells. Antibodies to GITR have been shown to promote an anti- ... PD-1 - short for Programmed Death 1 (PD-1) receptor, has two ligands, PD-L1 and PD-L2. This checkpoint is the target of Merck ... Binding with its two ligands are CD80 and CD86, expressed on dendritic cells, prompts T cell expansion. CD28 was the target of ...
*  CD134
... its ligand, OX40L, is also not expressed on resting antigen presenting cells, but is following their activation. Expression of ... CTLA-4 is down-regulated following OX40 engagement in vivo and the OX40-specific TRAF3 DN defect was partially overcome by CTLA ... TRAF3 may be linked to OX40-mediated memory T cell expansion and survival, and point to the down-regulation of CTLA-4 as a ... Arch RH, Thompson CB (Jan 1998). "4-1BB and Ox40 are members of a tumor necrosis factor (TNF)-nerve growth factor receptor ...
*  Lymphotoxin beta receptor
The encoded protein and its ligand play a role in the development and organization of lymphoid tissue and transformed cells. ... 28 (4): 169-75. doi:10.1016/j.it.2007.02.005. PMID 17336158. Browning JL, Ngam-ek A, Lawton P, et al. (1993). "Lymphotoxin beta ... 271 (25): 14661-4. doi:10.1074/jbc.271.25.14661. PMID 8663299. Matsumoto M, Hsieh TY, Zhu N, et al. (1997). "Hepatitis C virus ... 1998). "TRAF-4 expression in epithelial progenitor cells. Analysis in normal adult, fetal, and tumor tissues". Am. J. Pathol. ...
*  Protein phosphorylation
Binding of a ligand to a monomeric receptor tyrosine kinase stabilizes interactions between two monomers to form a dimer, after ... 147 (4): 934-946. doi:10.1016/j.cell.2011.08.052. Holt LJ, Tuch BB, Villén J, Johnson AD, Gygi SP, Morgan DO (2009). "Global ... 37 (Pt 4): 627-641. doi:10.1042/BST0370627. ISSN 1470-8752. PMID 19614568. van Weeren PC, de Bruyn KM, de Vries-Smits AM, van ... 4 (5): E127-130. doi:10.1038/ncb0502-e127. ISSN 1465-7392. PMID 11988757. "The Nobel Prize in Physiology or Medicine 1992". www ...
*  List of OMIM disorder codes
... due to ligand-defective apo B; 144010; APOB Hypercholesterolemia, familial; 143890; LDLR Hypercholesterolemia, familial, 3; ... 1BB; 612877; DSG2 Cardiomyopathy, dilated, 1CC; 613122; NEXN Cardiomyopathy, dilated, 1D; 601494; TNNT2 Cardiomyopathy, dilated ... 4; 604352; GPR98 COPD, rate of decline of lung function in; 606963; MMP1 Coproporphyria; 121300; CPOX Cornea plana congenita, ... KRAS Noonan syndrome 4; 610733; SOS1 Noonan syndrome 5; 611553; RAF1 Noonan syndrome 6; 613224; NRAS Noonan-like syndrome with ...
4-1BB ligand - Wikipedia  4-1BB ligand - Wikipedia
Ligand at the US National Library of Medicine Medical Subject Headings (MeSH) ... 4-1BB is a type 2 transmembrane glycoprotein receptor belonging to the TNF superfamily, expressed on activated T Lymphocytes.[1 ... 4-1BBL (4-1BB ligand) is found on APCs (antigen presenting cells) and binds to 4-1BB. ... Retrieved from "https://en.wikipedia.org/w/index.php?title=4-1BB_ligand&oldid=842807712" ...
more infohttps://en.wikipedia.org/wiki/4-1BB_ligand
Anti-Human 4-1BB Ligand  Anti-Human 4-1BB Ligand
Immunogen: E.coli derived Recombinant Human 4-1BB Ligand (PeproTech catalog# 310-11) ... Anti-Human 4-1BBL specific antibody was purified by affinity chromatography employing immobilized Human 4-1BBL matrix. ... This antigen affinity purified antibody, in conjunction with PeproTech's Biotinylated Anti-Human 4-1BBL (500-P169Bt) as a ... Preparation: Produced from sera of rabbits pre-immunized with highly pure recombinant Human 4-1BBL. ...
more infohttps://www.peprotech.com/en/anti-human-4-1bb-ligand-2
4-1BB Ligand Human E. coli | BioVendor  4-1BB Ligand Human E. coli | BioVendor
4-1BB Ligand. By Technical Data. 4-1BB Ligand - Proteins. 4-1BB Ligand - Recombinant protein - Proteins. Human - 4-1BB Ligand ... 4-1BBL binds to its receptor 4-1BB and provides a co-stimulatory signal for T cell activation and expansion. The human 4-1BBL ... 4-1BBL, a member of the TNF superfamily, is expressed in B cells, dendritic cells, activated T cells and macrophages. ... 4-1BB Ligand - from E. coli - Proteins. Recombinant protein - Proteins. Human - Recombinant protein - Proteins. Recombinant ...
more infohttps://www.biovendor.com/4-1bb-ligand-human-e-coli-1
PECy7 anti-human CD137L 4-1BB Ligand Antibody, 4-1BB Ligand, 5F4  PECy7 anti-human CD137L 4-1BB Ligand Antibody, 4-1BB Ligand, 5F4
4-1BB ligand, also known as CDw137L, is a 97 kD member of the TNF superfamily mainly expressed on APCs, activated B and T cells ... It has been reported to be important in T cell proliferation and cytokine production through interaction with 4-1BB receptor. 4 ... 1BB ligand appears to be able to act as a c ... Ligand Receptor 4-1BB (CDw137) Cell Type Antigen-presenting ... 4-1BBL, CDw137L, TNFSF9, 41BBL Isotype Mouse IgG1, κ Ave. Rating Submit a Review Product Citations publications Human T ...
more infohttps://www.biolegend.com/fr-fr/products/pecy7-anti-human-cd137l-4-1bb-ligand-antibody-16567
4-1BB Ligand | CTD  4-1BB Ligand | CTD
CD137 Ligand , Tumor Necrosis Factor (Ligand) Superfamily, Member 9 , Tumor Necrosis Factor Ligand Superfamily Member 9 ... The ligand is specific for the 4-1BB RECEPTOR and may play a role in inducing the proliferation of activated peripheral blood T ... 4-1BB Ligand Equivalent Terms 4 1BB Ligand , 4 1BBL Protein , 4-1BBL Protein , ...
more infohttp://ctdbase.org/detail.go?type=chem&acc=D053330
4-1BB Ligand | Profiles RNS  4-1BB Ligand | Profiles RNS
The ligand is specific for the 4-1BB RECEPTOR and may play a role in inducing the proliferation of activated peripheral blood T ... "4-1BB Ligand" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject ... This graph shows the total number of publications written about "4-1BB Ligand" by people in this website by year, and whether " ... Below are the most recent publications written about "4-1BB Ligand" by people in Profiles. ...
more infohttps://profiles.rush.edu/display/14282
4-1BBL Antibodies (4-1BB Ligand) | Bio-Rad  4-1BBL Antibodies (4-1BB Ligand) | Bio-Rad
We have brought together our full range of anti-4-1BBL antibodies in one place, making it easy for you to find exactly what you ... Our range of 4-1BBL antibodies (also known as 4-1BB Ligand / CD137L) come in a variety of different formats and to a number of ... Controls Anti-Biotherapeutic Antibodies Quality Control and Characterization Characterization of critical reagents for ligand ...
more infohttps://www.bio-rad-antibodies.com/4-1bbl-cd137l-antibody-range.html
Human CD137 (4-1BB)-Ligand - Premium and research grade - Cytokines and growth factors - MACS Cell Culture and Stimulation -...  Human CD137 (4-1BB)-Ligand - Premium and research grade - Cytokines and growth factors - MACS Cell Culture and Stimulation -...
Ligand is a recombinant protein optimized for use in cell culture, differentiation studies, and functional assays. ... Like other Ligands from the TNFSF family, active CD137-Ligand is expected to form a non-covalent homotrimer. ... CD137-Ligand, also known as 4-1BB-Ligand or TNFRSF9-Ligand, is the natural agonist of the CD137 receptor, and a member of the ... CD137-Ligand is expressed on antigen presenting cells, such as dendritic cells, B cells, and macrophages. The binding of CD137- ...
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4-1BB Ligand (4-1BBL, 4-1BB-L, CD137L, CD157L, Homolog of Mouse 4-1BB-L, Homolog of Mouse 4-1BBL, ILA Ligand (TNF-related),...  4-1BB Ligand (4-1BBL, 4-1BB-L, CD137L, CD157L, Homolog of Mouse 4-1BB-L, Homolog of Mouse 4-1BBL, ILA Ligand (TNF-related),...
ILA Ligand (TNF-related), Ly63L, Receptor 4-1BB Ligand, Tumor Necrosis Factor (Ligand) Superfamily Member 9), 0004-01V - Get ... 4-1BB Ligand (4-1BBL, 4-1BB-L, CD137L, CD157L, Homolog of Mouse 4-1BB-L, Homolog of Mouse 4-1BBL, ... 1993) Molecular cloning of a ligand for the inducible T cell gene 4-1BB: a member of an emerging family of cytokines with ... Ligand) Superfamily Member 9). Cat no: 0004-01V. Supplier: United States Biological ...
more infohttp://biosave.com/products/4-1bb-ligand-4-1bbl-4-1bb-l-cd137l-cd157l-homolog-of-mouse-4-1bb-l-homolog-of-mouse-4-1bbl-ila-ligand-tnf-related-ly63l-receptor-4-1bb-ligand-tumor-necrosis-factor-ligand-superfamily-member-9-0004-01v
Immunotherapy of Cancer with 4-1BB | Molecular Cancer Therapeutics  Immunotherapy of Cancer with 4-1BB | Molecular Cancer Therapeutics
CD137 ligand mediates opposite effects in human and mouse NK cells and impairs NK-cell reactivity against human acute myeloid ... CD137 and CD137 ligand constitutively coexpressed on human T and B leukemia cells signal proliferation and survival. Int J ... Mice deficient for CD137 ligand are predisposed to develop germinal center-derived B-cell lymphoma. Blood 2009;114:2280-9. ... CD137 ligand, a member of the tumor necrosis factor family, regulated immune responses via reverse signal transduction. J ...
more infohttps://mct.aacrjournals.org/content/11/5/1062?ijkey=7d45a39edf2a62cf486438292145f3d80bd97112&keytype2=tf_ipsecsha
TNF Superfamily research area  TNF Superfamily research area
... survival and death through the activation of multiple signal transduction pathways by ligand mediated trimerization and the ...
more infohttps://www.peprotech.com/ko/tnf-superfamily
Products in Recombinant Proteins on Thomas Scientific  Products in Recombinant Proteins on Thomas Scientific
found in: Murine MEC (CCL28), Fibroblast Growth Factor-Basic; Bovine FGF-Basic, 4-1BB Receptor/TNFRSF9, Human, Ebola virus-like ... B-cell activating factor (BlyS), also known as BAFF, TALL-1, TNAK, and zTNF4, is a TNF ligand superfamily member and has been ...
more infohttps://www.thomassci.com/nav/cat1/recombinantproteins/0
Generating High-Quality Biotinylated Proteins  Generating High-Quality Biotinylated Proteins
OX40 Ligand. PCSK9. PD-1. PD-L1. PD-L2. Prolactin. Protein L. ROR1. ROR2. SCF. Siglec-2. Siglec-3. ... Figure 4. Biotinylated Human PD-1(Cat. No. PD1-H82F1(at 1 μg/mL (5 μL/well) can bind Human PDL1 (Cat. No. PD1-H5229) with a ... Figures 4 and 5 demonstrate that the biotinylated PD1 can be applied to AlphaLISA to detect the binding activity with its ... ligand PD-L1 and PD-L2. Figures 6 and 7 demonstrate that the affinity between protein and therapeutic antibodies in SPR assay ...
more infohttps://www.news-medical.net/whitepaper/20181109/Generating-High-Quality-Biotinylated-Proteins.aspx
R Recombinant Cynomolgus Monkey 4-1BB/TNFRSF9 Fc Chimera Protein, Carrier-free
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R Recombinant Cynomolgus Monkey 4-1BB/TNFRSF9 Fc Chimera Protein, Carrier-free Quantity: 100µg Life Sciences:Protein Biology: ... The Recombinant Cynomolgus 4-1BB/TNFRSF9 Fc Chimera Protein is derived from HEK293. The Recombinant Cynomolgus 4-1BB/TNFRSF9 Fc ... 4-1BB ligand receptor; 41BB; 4-1BB; CD137 antigen; CD137; CD137MGC2172; CDw137; FLJ43501; ILA; ILAhomolog of mouse 4-1BB; ... R&D Systems Recombinant Cynomolgus Monkey 4-1BB/TNFRSF9 Fc Chimera Protein, Carrier-free ...
more infohttps://www.fishersci.com/shop/products/recombinant-cynomolgus-monkey-4-1bb-tnfrsf9-fc-chimera-protein-carrier-free/93244B100
TNFRSF9 Gene - GeneCards | TNR9 Protein | TNR9 Antibody  TNFRSF9 Gene - GeneCards | TNR9 Protein | TNR9 Antibody
T Cell Co-Signaling Pathway: Ligand-Receptor Interactions. T Cell Co-Signaling Pathway: Ligand-Receptor Interactions ... Characterization of human homologue of 4-1BB and its ligand. (PMID: 7622190) Zhou Z … Kwon BS (Immunology letters 1995) 3 4 22 ... 4) Ensembl transcripts including schematic representations, and UCSC links where relevant :. * ENST00000377507 (uc057bxz.1) ... Molecular and biological characterization of human 4-1BB and its ligand. (PMID: 8088337) Alderson MR … Din WS (European journal ...
more infohttp://www.genecards.org/cgi-bin/carddisp.pl?gene=TNFRSF9
TNFSF9 Gene - GeneCards | TNFL9 Protein | TNFL9 Antibody  TNFSF9 Gene - GeneCards | TNFL9 Protein | TNFL9 Antibody
T Cell Co-Signaling Pathway: Ligand-Receptor Interactions. *TNF Superfamily Pathway: Human Ligand-Receptor Interactions and ... Tumor necrosis factor ligand superfamily member 9 Protein Accession:. P41273. Secondary Accessions: *Q2M3S2 ... The ligand encoded by this gene, TNFSF9/4-1BBL, has been shown to reactivate anergic T lymphocytes in addition to promoting T ... TNF Superfamily Pathway: Human Ligand-Receptor Interactions and their Associated Functions. TNF Superfamily Pathway: Human ...
more infohttp://www.genecards.org/cgi-bin/carddisp.pl?gene=TNFSF9
IL-27 is required for shaping the magnitude, affinity distribution, and memory of T cells responding to subunit immunization |...  IL-27 is required for shaping the magnitude, affinity distribution, and memory of T cells responding to subunit immunization |...
2012) Type I IFN-dependent T cell activation is mediated by IFN-dependent dendritic cell OX40 ligand expression and is ... 4C). However, by monitoring the ratio of WT/IL-27RαKO OT-1s, we observed a striking increase in the ratio of WT to IL-27RαKO OT ... 4. IL-27 shapes T-cell memory, function, and survival. (A) Memory expansion assay of WT and IL-27RαKO mixed BMCs were generated ... 4D). Thus, either the survival of IL-27RαKO T cells was compromised past day 3 or their division was reduced compared with WT. ...
more infohttp://www.pnas.org/content/111/46/16472?ijkey=9ede4576813f80c7955b1eb5c23c0f3d1f831135&keytype2=tf_ipsecsha
Cancer Recombinant Proteins | ProSci  Cancer Recombinant Proteins | ProSci
We offer a plethora of cancer recombinant proteins to fit your research needs. Buy your recombinant proteins online from ProSci today.
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Recombinant Proteins Production | Buy Recombinant Proteins  Recombinant Proteins Production | Buy Recombinant Proteins
ProSci offers recombinant proteins for all levels of research to help analyze biological interactions. Find the recombinant proteins you need today.
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Ligation of 4-1BB (CDw137) Regulates Graft-Versus-Host Disease, Graft-Versus-Leukemia, and Graft Rejection in Allogeneic Bone...  Ligation of 4-1BB (CDw137) Regulates Graft-Versus-Host Disease, Graft-Versus-Leukemia, and Graft Rejection in Allogeneic Bone...
Involvement of CD40 ligand-CD40 and CTLA4-B7 pathways in murine acute graft-versus-host disease induced by allogeneic T cells ... α4-1BB mAb increased the graft-vs-leukemia effect of a suboptimal number of donor splenocytes given later post bone marrow ... Molecular cloning of a ligand for the inducible T cell gene 4-1BB: a member of an emerging family of cytokines with homology to ... CD62 ligand) on CD4+ T cells was similar for each one in the two groups (data not shown). Restimulation of washed control or ...
more infohttp://www.jimmunol.org/content/166/5/3174
  • Immunotherapy targeting CD8+ T cells with agonistic anti-4-1BB (CD137) monoclonal antibody (mAb) fulfills these requirements because 4-1BB-mediated signals are biased toward CD8+ T cells, promoting their survival, differentiation, and acquisition of potent cytolytic properties ( 1 ). (aacrjournals.org)
  • Despite the expression of 4-1BB on both CD4 + and CD8 + T cells, the majority of data available to date has suggested that CD8 + T cells are affected to a greater extent by agonistic anti-4-1BB mAbs than CD4 + T cells ( 16 , 17 , 18 , 19 ). (jimmunol.org)
  • 13-21 Allergens induce CD4+ T helper cells to produce type 2 (Th2) cytokines such as IL-4, IL-5, IL-6, IL-10, and IL-13. (bmj.com)
  • B-cell activating factor (BlyS), also known as BAFF, TALL-1, TNAK, and zTNF4, is a TNF ligand superfamily member and has been designated TNFSF13B. (thomassci.com)
  • The human 4-1BBL gene codes for a 254 amino acid type II transmembrane containing a 28 amino acid cytoplasmic domain, a 21 amino acid transmembrane domain and a 205 amino acid extracellular domain. (biovendor.com)
  • The soluble form of 4-1BBL contains the TNF-like portion of the extracellular domain of 4-1BBL. (biovendor.com)
  • The members of the TNF Superfamily are responsible for the regulation of cellular differentiation, survival and death through the activation of multiple signal transduction pathways by ligand mediated trimerization and the resulting recruitment of several intracellular adaptors. (peprotech.com)
  • In summary, 4-1BB ligation is a potent regulator of CD4 + and CD8 + T cell-mediated allogeneic responses in vivo. (jimmunol.org)
  • Modifying the ligation of 4-1BB represents a new approach to altering the graft-vs-host disease and graft-vs-leukemia effects of allogeneic T cells post bone marrow transplantation. (jimmunol.org)
  • Biological effects of 4-1BB signaling. (aacrjournals.org)
  • Among its related pathways are T Cell Co-Signaling Pathway: Ligand-Receptor Interactions and Akt Signaling . (genecards.org)
  • Results obtained with anti-4-1BB mAb infusion into tumor-bearing mice indicated that both CD4 + and CD8 + T cells were required for an optimal anti-tumor immune response, indicating that 4-1BB receptor signaling augmented T helper support of CD8 + CTL responses ( 20 ). (jimmunol.org)
  • Currently, a humanized anti-4-1BB is in clinical trials in patients with solid tumors, including melanoma, renal carcinoma, and ovarian cancer, and so far seems to have a favorable toxicity profile. (aacrjournals.org)
  • Furthermore, the adoptive transfer of ex vivo anti-4-1BB-activated CD8+ T cells from previously tumor-treated animals efficiently inhibits progression of tumors in recipient mice that have been inoculated with fresh tumors. (aacrjournals.org)
  • By quantifying graft-vs-host disease alloresponses in vivo, we demonstrate that both CD4 + and CD8 + T cell-mediated alloresponses are regulated by 4-1BB/4-1BB ligand interactions to approximately the same extent. (jimmunol.org)
  • In vivo CTL generation against both alloantigen ( 17 ) and tumor Ag-bearing targets ( 20 ) can be enhanced by the administration of a mitogenic anti-4-1BB mAb infusion. (jimmunol.org)
  • This study was conducted to determine the effect of 4-1BB receptor/4-1BBL interaction on regulating alloresponses in vivo. (jimmunol.org)
  • Functional 4-1BB expression has also been observed on myeloid cells, such as monocytes, neutrophils, mast cells, and eosinophils ( 6 ). (aacrjournals.org)
  • The importance of the 4-1BB pathway has been underscored in a number of diseases, including cancer. (aacrjournals.org)
  • 4-6 The prevalence of allergic diseases including asthma has increased significantly over the past 40 years. (bmj.com)