22 results on '"Sally T. Ishizaka"'
Search Results
2. Therapeutical targeting of nucleic acid-sensing Toll-like receptors prevents experimental cerebral malaria
- Author
-
Douglas T. Golenbock, Marc Lamphier, Bernardo S. Franklin, Ricardo T. Gazzinelli, Marco Antonio Ataide, Jeffrey Rose, Sally T. Ishizaka, Hans J. Hansen, Fabian Gusovsky, Rosane B. de Oliveira, and Wanjun Zheng
- Subjects
Pathogenesis ,Multidisciplinary ,Innate immune system ,Cerebral Malaria ,parasitic diseases ,Immunology ,TLR9 ,Plasmodium berghei ,TLR8 ,Biology ,Receptor ,biology.organism_classification ,Proinflammatory cytokine - Abstract
Excessive release of proinflammatory cytokines by innate immune cells is an important component of the pathogenic basis of malaria. Proinflammatory cytokines are a direct output of Toll-like receptor (TLR) activation during microbial infection. Thus, interference with TLR function is likely to render a better clinical outcome by preventing their aberrant activation and the excessive release of inflammatory mediators. Herein, we describe the protective effect and mechanism of action of E6446, a synthetic antagonist of nucleic acid-sensing TLRs, on experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA. We show that in vitro, low doses of E6446 specifically inhibited the activation of human and mouse TLR9. Tenfold higher concentrations of this compound also inhibited the human TLR8 response to single-stranded RNA. In vivo, therapy with E6446 diminished the activation of TLR9 and prevented the exacerbated cytokine response observed during acute Plasmodium infection. Furthermore, severe signs of ECM, such as limb paralysis, brain vascular leak, and death, were all prevented by oral treatment with E6446. Hence, we provide evidence that supports the involvement of nucleic acid-sensing TLRs in malaria pathogenesis and that interference with the activation of these receptors is a promising strategy to prevent deleterious inflammatory responses that mediate pathogenesis and severity of malaria.
- Published
- 2011
3. E6020: a synthetic Toll-like receptor 4 agonist as a vaccine adjuvant
- Author
-
Sally T. Ishizaka and Lynn D. Hawkins
- Subjects
Agonist ,medicine.drug_class ,medicine.medical_treatment ,Immunology ,Phospholipid ,Biology ,Pharmacology ,Lipid A ,chemistry.chemical_compound ,Adjuvants, Immunologic ,In vivo ,Drug Discovery ,medicine ,Animals ,Humans ,Receptor ,Phospholipids ,Vaccines ,Toll-like receptor ,In vitro ,Toll-Like Receptor 4 ,chemistry ,Molecular Medicine ,Adjuvant - Abstract
Safe and cost-effective adjuvants are a critical component to enhance the efficacy of subunit vaccines. Studies have demonstrated that modified natural lipid As derived from enterobacterial lipopolysaccharides, which are agonists of Toll-like receptor 4, are beneficial to vaccine performance. The synthetic phospholipid dimer, E6020, mimics the physicochemical and biological properties of many of the natural lipid As derived from gram-negative bacteria. Similar to its natural counterparts, E6020, which was discovered and developed by Eisai, agonizes Toll-like receptor 4, albeit in an attenuated fashion, eliciting an immunostimulatory response that is conducive to use as a vaccine adjuvant. The derivation of E6020, along with physicochemical properties and in vitro and in vivo studies of immunostimulation and adjuvant activity, are reviewed as a background to its imminent assessment in the clinic.
- Published
- 2007
4. LPS binding protein does not participate in the pharmacokinetics of E5564
- Author
-
Tsutomu Yoshimura, Sally T. Ishizaka, Rika Ueda, Tsutomu Kawata, and Kazuhiro Kaneko
- Subjects
Lipopolysaccharides ,medicine.medical_specialty ,Lipopolysaccharide ,Immunology ,030226 pharmacology & pharmacy ,Microbiology ,Lipid A ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Pharmacokinetics ,Internal medicine ,medicine ,Animals ,Chemical Precipitation ,Distribution (pharmacology) ,Drug Interactions ,Molecular Biology ,Mice, Knockout ,Manganese ,Mice, Inbred BALB C ,Membrane Glycoproteins ,biology ,Heparin ,Antagonist ,Anticoagulants ,Cell Biology ,Shock, Septic ,Mice, Inbred C57BL ,Infectious Diseases ,Endocrinology ,chemistry ,Biochemistry ,Antibody Formation ,biology.protein ,Female ,lipids (amino acids, peptides, and proteins) ,Antibody ,Carrier Proteins ,Lipopolysaccharide binding protein ,Acute-Phase Proteins ,030215 immunology ,Lipoprotein - Abstract
E5564, a lipid A analogue, is a potent antagonist of lipopolysaccharide (LPS). Clinically, E5564 was developed as a possible therapy for treatment of sepsis and septic shock. Surface plasmon resonance (SPR) analysis indicates that E5564 binds to LPS binding protein (LBP), in a manner similar to LPS. Gel-filtration radioactive chromatograms of [14C]-E5564 in plasma revealed that E5564 initially distributes to the lipoprotein fractions, separated from high-density lipoprotein (HDL); the bound fraction is then released and binds to HDL. Similar results were obtained by heparin-manganese precipitation. At doses of E5564 relevant to its clinical use ( i.e. 6 µg/ml), antibodies against LBP did not influence either the distribution of E5564 to non-HDL lipoprotein fractions or the transfer of E5564 from non-HDLs to HDL. Under these conditions, transfer of E5564 to HDL occurs similarly in the plasma of LBP knockout (KO) mice as in the plasma from wild-type mice. In addition, plasma clearance of E5564 in LBP KO mice is similar to that of wild-type mice. Thus, LBP binds E5564 in a manner similar to LPS, but does not play a role in E5564 redistribution/binding to lipoprotein and plasma clearance.
- Published
- 2004
5. A Novel Class of Endotoxin Receptor Agonists with Simplified Structure, Toll-Like Receptor 4-Dependent Immunostimulatory Action, and Adjuvant Activity
- Author
-
Fabian Gusovsky, Jeffrey Rose, Jesse Chow, Bruce Decosta, Wendy Gavin, Donna W. Young, Hua Yang, Huiming Zhang, Pamela Mcguinness, Nault Anneliese, Maureen A. Mullarkey, Lynn D. Hawkins, Zhaoyang Meng, Melinda Przetak, Hu Yang, Sally T. Ishizaka, and Daniel P. Rossignol
- Subjects
Adult ,Lipopolysaccharides ,Male ,Adolescent ,Lipopolysaccharide ,Receptors, Cell Surface ,Pharmacology ,Biology ,Disaccharides ,Transfection ,Cell Line ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Adjuvants, Immunologic ,In vivo ,Animals ,Drosophila Proteins ,Humans ,Receptors, Immunologic ,Receptor ,Mice, Inbred BALB C ,Toll-like receptor ,Membrane Glycoproteins ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Molecular Mimicry ,Toll-Like Receptors ,NF-kappa B ,Toxoid ,Middle Aged ,In vitro ,Toll-Like Receptor 4 ,Lipid A ,chemistry ,TLR4 ,Molecular Medicine ,Female ,lipids (amino acids, peptides, and proteins) ,Cell activation - Abstract
A series of novel, synthetic compounds containing lipids linked to a phosphate-containing acyclic backbone are shown to have similar biological properties to lipopolysaccharide (LPS). These compounds showed intrinsic agonistic properties when tested for their ability to stimulate tumor necrosis factor-alpha in human whole blood and interleukin-6 in U373 human glioblastoma cells without added LPS coreceptor CD14. The presence of the LPS antagonist E5564 completely blocked responses, suggesting that the novel compounds and LPS share a common mechanism of cell activation. Stereoselectivity of the molecules was observed in vitro; compounds with an R,R,R,R-configuration were strongly agonistic, whereas compounds with an R,S,S,R-configuration were much weaker in their activity on human whole blood and U373 cells. We also tested the effect of the compounds in cells transfected with the LPS receptor Toll-like receptor 4 (TLR4), with similar results, further supporting a shared mechanism with LPS. This was confirmed in vivo where the agonists failed to elicit cytokine responses in C3H/HeJ mice lacking TLR4 signaling. Because LPS-like molecules enhance immune responses, the compounds were mixed with tetanus toxoid and administered to mice in an immunization protocol to test for adjuvant activity. They enhanced the generation of specific antibodies against tetanus toxoid. Our results indicate that these unique compounds behave as agonists of TLR4, resulting in responses similar to those elicited by LPS. They display adjuvant activity in vivo and may be useful for the development of vaccine therapies.
- Published
- 2002
6. The Extra Domain A of Fibronectin Activates Toll-like Receptor 4
- Author
-
Yoshinori Okamura, Donna W. Young, Jerome F. Strauss, Elliot S. Jerud, Jeffrey Rose, Jesse C. Chow, Michiko Watari, and Sally T. Ishizaka
- Subjects
Lipopolysaccharides ,Hot Temperature ,Time Factors ,Biochemistry ,law.invention ,Mice ,law ,Drosophila Proteins ,Receptor ,Polymyxin B ,Mice, Inbred C3H ,Toll-like receptor ,Membrane Glycoproteins ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,Toll-Like Receptors ,Exons ,Recombinant Proteins ,Anti-Bacterial Agents ,Interleukin-10 ,Lipid A ,Matrix Metalloproteinase 9 ,Antigens, Surface ,Recombinant DNA ,lipids (amino acids, peptides, and proteins) ,Signal transduction ,Plasmids ,Signal Transduction ,Blotting, Western ,Lymphocyte Antigen 96 ,Receptors, Cell Surface ,Transfection ,Cell Line ,Animals ,Humans ,Molecular Biology ,Inflammation ,Dose-Response Relationship, Drug ,HEK 293 cells ,Cell Biology ,Molecular biology ,Fibronectins ,Protein Structure, Tertiary ,Enzyme Activation ,Toll-Like Receptor 4 ,Fibronectin ,Cell culture ,biology.protein ,TLR4 ,Spleen - Abstract
Cellular fibronectin, which contains an alternatively spliced exon encoding type III repeat extra domain A (EDA), is produced in response to tissue injury. Fragments of fibronectin have been implicated in physiological and pathological processes, especially tissue remodeling associated with inflammation. Because EDA-containing fibronectin fragments produce cellular responses similar to those provoked by bacterial lipopolysaccharide (LPS), we examined the ability of recombinant EDA to activate Toll-like receptor 4 (TLR4), the signaling receptor stimulated by LPS. We found that recombinant EDA, but not other recombinant fibronectin domains, activates human TLR4 expressed in a cell type (HEK 293 cells) that normally lacks this Toll-like receptor. EDA stimulation of TLR4 was dependent upon co-expression of MD-2, a TLR4 accessory protein. Unlike LPS, the activity of EDA was heat-sensitive and persisted in the presence of the LPS-binding antibiotic polymyxin B and a potent LPS antagonist, E5564, which completely suppressed LPS activation of TLR4. These observations provided a mechanism by which EDA-containing fibronectin fragments promote expression of genes involved in the inflammatory response.
- Published
- 2001
7. Novel small molecule inhibitors of TLR7 and TLR9: mechanism of action and efficacy in vivo
- Author
-
Yongchun Shen, Thorsten R. Mempel, Zhao Yan J, Melvin J. Yu, Sally T. Ishizaka, Wanjun Zheng, Hua Yang, Fabian Gusovsky, Jeffrey Rose, Melinda Genest, Christopher Rowbottom, Mark Spyvee, Natalie C. Twine, Marc Lamphier, Eicke Latz, Hans J. Hansen, Diana Liu, Christina J. Shaffer, Carrie Liu, and Jesse Chow
- Subjects
Down-Regulation ,Pharmacology ,Biology ,AMP-Activated Protein Kinases ,MAP Kinase Kinase Kinase 5 ,p38 Mitogen-Activated Protein Kinases ,Cell Line ,Small Molecule Libraries ,Mice ,Thioredoxins ,In vivo ,medicine ,Animals ,Receptor ,Systemic lupus erythematosus ,Membrane Glycoproteins ,Podocytes ,TLR9 ,TLR7 ,medicine.disease ,Small molecule ,In vitro ,Oxidative Stress ,Mechanism of action ,Toll-Like Receptor 7 ,Doxorubicin ,Toll-Like Receptor 9 ,Molecular Medicine ,medicine.symptom ,Carrier Proteins ,Reactive Oxygen Species ,Signal Transduction - Abstract
The discovery that circulating nucleic acid-containing complexes in the serum of autoimmune lupus patients can stimulate B cells and plasmacytoid dendritic cells via Toll-like receptors 7 and 9 suggested that agents that block these receptors might be useful therapeutics. We identified two compounds, AT791 {3-[4-(6-(3-(dimethylamino)propoxy)benzo[d]oxazol-2-yl)phenoxy]-N,N-dimethylpropan-1-amine} and E6446 {6-[3-(pyrrolidin-1-yl)propoxy)-2-(4-(3-(pyrrolidin-1-yl)propoxy)phenyl]benzo[d]oxazole}, that inhibit Toll-like receptor (TLR)7 and 9 signaling in a variety of human and mouse cell types and inhibit DNA-TLR9 interaction in vitro. When administered to mice, these compounds suppress responses to challenge doses of cytidine-phosphate-guanidine (CpG)-containing DNA, which stimulates TLR9. When given chronically in spontaneous mouse lupus models, E6446 slowed development of circulating antinuclear antibodies and had a modest effect on anti-double-stranded DNA titers but showed no observable impact on proteinuria or mortality. We discovered that the ability of AT791 and E6446 to inhibit TLR7 and 9 signaling depends on two properties: weak interaction with nucleic acids and high accumulation in the intracellular acidic compartments where TLR7 and 9 reside. Binding of the compounds to DNA prevents DNA-TLR9 interaction in vitro and modulates signaling in vivo. Our data also confirm an earlier report that this same mechanism may explain inhibition of TLR7 and 9 signaling by hydroxychloroquine (Plaquenil; Sanofi-Aventis, Bridgewater, NJ), a drug commonly prescribed to treat lupus. Thus, very different structural classes of molecules can inhibit endosomal TLRs by essentially identical mechanisms of action, suggesting a general mechanism for targeting this group of TLRs.
- Published
- 2013
8. Assessment of the translational value of mouse lupus models using clinically relevant biomarkers
- Author
-
Andrew T. Bender, Judith Oestreicher, Qiongfang Cao, Sally T. Ishizaka, Sandeep Akare, Yin Wu, Yueyun Ding, Melinda Genest, and Mackey Matthew
- Subjects
Disease ,Biology ,Translational Research, Biomedical ,Mice ,Species Specificity ,Physiology (medical) ,medicine ,Animals ,Humans ,Lupus Erythematosus, Systemic ,Autoantibodies ,Oligonucleotide Array Sequence Analysis ,Autoimmune disease ,Mice, Inbred BALB C ,Lupus erythematosus ,Systemic lupus erythematosus ,Mice, Inbred NZB ,Terpenes ,Biochemistry (medical) ,Public Health, Environmental and Occupational Health ,Autoantibody ,General Medicine ,Gene signature ,medicine.disease ,Arthritis, Experimental ,Lupus Nephritis ,Disease Models, Animal ,Drug development ,Mice, Inbred DBA ,Immunology ,Experimental pathology ,Female ,Interferons ,Biomarkers - Abstract
Lupus is an autoimmune disease with a poorly understood etiology that manifests with a diverse pathology. This heterogeneity has been a challenge to clinical drug development efforts. A related difficulty is the uncertain translational power of animal models used for evaluating potential drug targets and candidate therapeutics, because it is unlikely that any 1 preclinical model will recapitulate the spectrum of human disease. Therefore, multiple models, along with an understanding of the immune mechanisms that drive them, are necessary if we are to use them to identify valid drug targets and evaluate candidate therapies successfully. To this end, we have characterized several different mouse lupus models and report their differences with respect to biomarkers and symptoms that are representative of the human disease. We compared the pristane-induced mouse lupus disease model using 3 different strains (DBA/1, SJL, BALB/c), and the spontaneous NZB x NZW F1(NZB/W) mouse model. We show that the models differ significantly in their autoantibody profiles, disease manifestations such as nephritis and arthritis, and expression of type I interferon-regulated genes. Similar to the NZB/W model, pristane-induced disease in SJL mice manifests with nephritis and proteinuria, whereas the pristane-treated DBA/1 mice develop arthritis and an interferon-driven gene signature that closely resembles that in human patients. The elucidation of each model's strengths and the identification of translatable biomarkers yields insight for basic lupus research and drug development, and should assist in the proper selection of models for evaluating candidate targets and therapeutic strategies.
- Published
- 2013
9. IgG Subtype Is Correlated with Efficiency of Passive Protection and Effector Function of Anti-Herpes Simplex Virus Glycoprotein D Monoclonal Antibodies
- Author
-
Priscilla Piacente, Eric M. Mishkin, Jillian Silva, and Sally T. Ishizaka
- Subjects
medicine.drug_class ,Herpesvirus 2, Human ,viruses ,medicine.medical_treatment ,Passive immunity ,Biology ,Antibodies, Viral ,medicine.disease_cause ,Monoclonal antibody ,Immunoglobulin G ,Subclass ,Virus ,Mice ,Viral Envelope Proteins ,medicine ,Animals ,Immunology and Allergy ,Mice, Inbred BALB C ,Effector ,Immunization, Passive ,Antibodies, Monoclonal ,Herpes Simplex ,Immunoglobulin Class Switching ,Virology ,Molecular biology ,Infectious Diseases ,Herpes simplex virus ,Mutation ,biology.protein ,Female ,Antibody - Abstract
IgG subclasses differ in their effector functions in a variety of in vitro assays. To assess the effect of antibody subclass differences on in vivo protective efficacy against herpes simplex virus (HSV), a series of subclass switch mutants was made from an anti-HSV glycoprotein D monoclonal antibody. Purified antibody was examined for the ability to protect against HSV-2 challenge in mice. IgG2a was found to be more effective than IgG1. This correlated both with activity in antibody-dependent cell-mediated cytotoxicity and with efficiency of complement-mediated neutralization. These data suggest that optimization of passive immunization against HSV requires consideration of antibody subclass.
- Published
- 1995
10. Baculovirus-expressed herpes simplex virus type 2 glycoprotein D is immunogenic and protective against lethal HSV challenge
- Author
-
S.L. Wu, Sally T. Ishizaka, C.D. Zarley, V. Landolfi, M. Blasiak, Eric M. Mishkin, N. Figueroa, and A.S. Abramovitz
- Subjects
Antigenicity ,medicine.drug_class ,T-Lymphocytes ,Gene Expression ,In Vitro Techniques ,Moths ,Biology ,Antibodies, Viral ,Lymphocyte Activation ,Recombinant virus ,medicine.disease_cause ,Monoclonal antibody ,Virus ,Cell Line ,Mice ,Viral Envelope Proteins ,Neutralization Tests ,medicine ,Animals ,Simplexvirus ,Cloning, Molecular ,chemistry.chemical_classification ,Mice, Inbred BALB C ,General Veterinary ,General Immunology and Microbiology ,Infectious dose ,Immunogenicity ,Public Health, Environmental and Occupational Health ,Herpes Simplex ,Virology ,Molecular biology ,Infectious Diseases ,Herpes simplex virus ,chemistry ,Molecular Medicine ,Female ,Glycoprotein ,Baculoviridae - Abstract
Herpes simplex virus type 2 glycoprotein D (gD2) was cloned and expressed in the baculovirus-Spodoptera frugiperda system. Milligram quantities of glycoprotein were recovered from suspension culture and subjected to purification by ion-exchange and immunoaffinity chromatography. The resultant purified gD existed as a homogeneous 57,500 MW monomeric species demonstrating reactivity with anti-gD monoclonal antibodies including those directed at a non-sequential neutralizing epitope of gD. Immunization of Balb/c mice with doses of 0.1-10.0 micrograms of AlPO4-absorbed gD resulted in elicitation of humoral and cellular responses to both HSV1 and HSV2 as well as to purified gD1 and gD2. Immunized mice receiving an infectious dose of 1 x 10(6) p.f.u. of HSV2 via the footpad route were significantly protected against infection at all doses tested when compared with unimmunized AlPO4 and uninoculated control animals.
- Published
- 1993
11. Modulators of Toll-Like Receptor (TLR) Signaling
- Author
-
Lynn D. Hawkins, Mark Spyvee, and Sally T. Ishizaka
- Subjects
TLR2 ,Toll-like receptor ,TLR6 ,TLR3 ,Immunology ,TLR4 ,TLR9 ,TLR7 ,Biology ,Receptor ,Bioinformatics - Abstract
Publisher Summary This chapter deals with the modulators of toll-like receptor (TLR) signaling. The rate of TLR-related publications has risen consistently over the past decade. Despite this increasing wealth of information, relatively few TLR modulators have been addresses in the chapter. Among the pharmaceutically relevant concepts, TLR4, TLR7, and TLR9 have been featured most prominently. In terms of development, the most advanced compound is TLR4 antagonist E5564, which is in Phase III sepsis trials. Also of interest is the TLR7/8/9 antagonist CPG 52364, which is in early clinical development for SLE. TLR2 (as a heterodimer with TLR1 or TLR6), MyD88, and IRAK-4 may also prove to be attractive therapeutic targets for various inflammatory diseases; however, few agents have been reported and these have not yet advanced beyond early discovery. This situation may change as recent publications have disclosed valuable structural information for TLR1/2, TLR2/6, TLR3, MyD88, and IRAK-4, which may help stimulate additional structure-based drug design efforts in these areas.
- Published
- 2010
12. Synthetic Toll-like receptor 4 agonist enhances vaccine efficacy in an experimental model of toxic shock syndrome
- Author
-
Robert G. Ulrich, Sally T. Ishizaka, Garry L. Morefield, Teri L. Kissner, and Lynn D. Hawkins
- Subjects
Microbiology (medical) ,Agonist ,Lipopolysaccharides ,Male ,Staphylococcus aureus ,medicine.drug_class ,medicine.medical_treatment ,Clinical Biochemistry ,Immunology ,Immunoglobulins ,Aluminum Hydroxide ,Biology ,Immunoglobulin G ,Microbiology ,Enterotoxins ,Mice ,Th2 Cells ,Adjuvants, Immunologic ,medicine ,Immunology and Allergy ,Animals ,Toll-like receptor ,Mice, Inbred BALB C ,Toxic shock syndrome ,Th1 Cells ,Vaccine efficacy ,medicine.disease ,Vaccine Research ,Shock, Septic ,Toll-Like Receptor 2 ,Bacterial vaccine ,Toll-Like Receptor 4 ,TLR2 ,Toll-Like Receptor 6 ,Bacterial Vaccines ,Models, Animal ,biology.protein ,Cytokines ,Adjuvant ,Signal Transduction - Abstract
The development of new protein subunit vaccines has stimulated the search for improved adjuvants to replace traditional aluminum-containing products. We investigated the adjuvant effects of a synthetic Toll-like receptor 4 (TLR4) agonist on vaccine efficacy in an experimental model of toxic shock syndrome. The TLR4 agonist E6020 has a simplified structure consisting of a hexa-acylated acyclic backbone. The vaccine examined is a recombinantly attenuated form of staphylococcal enterotoxin B (STEBVax). Using cells stably transfected with TLRs, E6020 transduced signals only through TLR4, suggesting monospecificity, while Escherichia coli 055:B5 lipopolysaccharide activated both the TLR2/6 heterodimer and TLR4. Coadministration of E6020 with STEBVax, by the intramuscular or intranasal route, induced significant levels of immunoglobulin G (IgG) in BALB/c mice. Further, increased IgG production resulted from the combination of E6020 with aluminum hydroxide adjuvant (AH). The antibody response to the vaccine coadministered with E6020 was a mixed Th1/Th2 response, as opposed to the Th2-biased response obtained with AH. Mice vaccinated with STEBVax coadministered with AH, TLR4 agonists, or a combination of both adjuvants were protected from toxic shock. Our data demonstrate the effectiveness of the synthetic TLR4 agonist E6020 as an alternative adjuvant for protein subunit vaccines that may also be used in combination with traditional aluminum-containing adjuvants.
- Published
- 2007
13. Novel synthetic LPS receptor agonists boost systemic and mucosal antibody responses in mice
- Author
-
Sally T. Ishizaka, Jeffrey Rose, Melinda Przetak, Lynn D. Hawkins, Jesse Chow, and Hongsheng Cheng
- Subjects
Lipopolysaccharide ,Ovalbumin ,medicine.medical_treatment ,Lipopolysaccharide Receptors ,Immunoglobulin E ,chemistry.chemical_compound ,Mice ,Th2 Cells ,Antigen ,Adjuvants, Immunologic ,medicine ,Tetanus Toxoid ,Animals ,Immunity, Mucosal ,Administration, Intranasal ,Mice, Inbred BALB C ,General Veterinary ,General Immunology and Microbiology ,biology ,Public Health, Environmental and Occupational Health ,Th1 Cells ,Interleukin-10 ,Infectious Diseases ,Lipid A ,chemistry ,Immunology ,Humoral immunity ,Antibody Formation ,Vaccines, Subunit ,biology.protein ,TLR4 ,Molecular Medicine ,Nasal administration ,Female ,Antibody ,Adjuvant - Abstract
Safe and cost-effective adjuvants are a critical requirement for subunit vaccine development. We report here the in vivo activity of a series of fully synthetic LPS receptor agonists that have been shown to activate NF-κB signaling through the Toll-like receptor 4 (TLR4). These compounds boost antibody responses to protein antigens when coadministered at microgram doses in mice. At these dosage levels no adverse effects are observed. Antibody responses are largely IgG1, with enhanced IgG2a, and down-regulated IgE as compared to alum adjuvanted immunization. Stimulation of Th1 is confirmed by enhanced γ-interferon production after in vitro antigen restimulation of spleen cells from mice immunized with the synthetic adjuvants. The adjuvants are active by both subcutaneous and intranasal routes of vaccine administration, and in the latter case can amplify both serum IgG and serum and mucosal IgA responses. The compounds must be administered at the same site with antigen to boost anti-vaccine antibody. These fully synthetic ligands of the innate immune system offer the potential for use as effective, safe, and nonbiologically-derived adjuvants.
- Published
- 2003
14. Combined systemic and mucosal immunization with microsphere-encapsulated inactivated simian immunodeficiency virus elicits serum, vaginal, and tracheal antibody responses in female rhesus macaques
- Author
-
Eric M. Mishkin, Preston A. Marx, Jay K. Staas, Agegnehu Gettie, Zimra R. Israel, David C. Montefiori, John H. Eldridge, Richard M. Gilley, and Sally T. Ishizaka
- Subjects
viruses ,Immunology ,Enzyme-Linked Immunosorbent Assay ,medicine.disease_cause ,Antibodies, Viral ,Virus ,chemistry.chemical_compound ,Neutralization Tests ,Virology ,Immunopathology ,medicine ,Animals ,Immunity, Mucosal ,biology ,Immunogenicity ,Viral Vaccines ,Simian immunodeficiency virus ,biology.organism_classification ,Macaca mulatta ,Microspheres ,Trachea ,Titer ,Infectious Diseases ,chemistry ,Humoral immunity ,Lentivirus ,Vagina ,Female ,Simian Immunodeficiency Virus ,Vaccinia - Abstract
We determined the efficacy of immunization with microsphere-encapsulated whole inactivated simian immunodeficiency virus (SIV) by combined systemic and mucosal administration to protect female rhesus macaques against vaginal challenge with homologous rhesus PBMC-grown SIVmac251. Animals in one group were primed and boosted intramuscularly. Two groups were primed intramuscularly and boosted either intratracheally or orally. A final group was primed by vaccinia/rgp140 scarification and subdivided for either intratracheal or oral boosting. Strong ELISA titers of circulating SIV-specific IgG and modest IgA responses were elicited in the animals primed intramuscularly. Intratracheal boosting in the intramuscularly primed macaques resulted in high bronchial alveolar wash (BAW) IgG and less pronounced IgA. SIV-specific vaginal wash (VW) IgG was also present in the intramuscular/intramuscular and intramuscular/intratracheal groups. Vaccinia/rgp140 priming gave low ELISA titers to whole SIV, and failed to elicit mucosal antibody regardless of the booster route. No animal in any group developed serum neutralizing antibody to homologous SIVmac251. On vaginal challenge none of the immunized groups was infected at a lesser frequency than the unimmunized controls. These data suggest that the use of microspheres in a combined parenteral and mucosal regimen is an effective method of eliciting IgG and IgA antibody at mucosal surfaces.
- Published
- 1999
15. Induction of mucosal antibody responses by microsphere-encapsulated formalin-inactivated simian immunodeficiency virus in a male urethral challenge model
- Author
-
Sally T. Ishizaka, John H. Eldridge, Agegnehu Gettie, Peter J. Dailey, David C. Montefiori, Zimra R. Israel, Jay K. Staas, Preston A. Marx, Eric M. Mishkin, and Richard M. Gilley
- Subjects
Male ,Time Factors ,viruses ,animal diseases ,Simian Acquired Immunodeficiency Syndrome ,medicine.disease_cause ,Antibodies, Viral ,Epitope ,Virus ,Immunity ,Formaldehyde ,Urethral Diseases ,medicine ,Animals ,Neutralizing antibody ,Immunity, Mucosal ,General Veterinary ,General Immunology and Microbiology ,biology ,Immunogenicity ,Public Health, Environmental and Occupational Health ,Viral Vaccines ,Simian immunodeficiency virus ,biology.organism_classification ,Virology ,Macaca mulatta ,Microspheres ,Infectious Diseases ,Vaccines, Inactivated ,Lentivirus ,Immunology ,Humoral immunity ,biology.protein ,Molecular Medicine ,Simian Immunodeficiency Virus - Abstract
Male rhesus macaques were immunized mucosally with microsphere-encapsulated formalin-inactivated simian immunodeficiency virus (SIV) particles in a test of immunogenicity and protection against mucosal SIV challenge. Tracheal boosting of animals that had been primed intramuscularly resulted in strong serum ELISA titers to SIV, and evidence of local IgA responses in broncho-alveolar washes. The bulk of the antibody response was against non-envelope epitopes. No neutralizing antibody was observed, and intraurethral challenge with cell-free rhesus-grown virus showed no evidence of protection against infection. Microsphere-based immunization efficiently raises local and system responses, but the resulting immunity to SIV is apparently not sufficient to protect against mucosal challenge.
- Published
- 1999
16. Abstract LB-324: A toll-like receptor 4 agonist enhances the efficacy of trastuzumab therapy and promotes adaptive immunity and long-term protection against a human ErbB-2 (HER2)-transfected syngeneic tumor in a human HER2 transgenic mouse model
- Author
-
Louis M. Weiner, Catherine Bingham, Yong Tang, Sally T. Ishizaka, Bruce A. Littlefield, Shangzi Wang, Rishi Surana, Kenneth McCarthy, Lynn D. Hawkins, Wei Xu, R. Katherine Alpaugh, and Igor Astsaturov
- Subjects
Agonist ,Genetically modified mouse ,Cancer Research ,Toll-like receptor ,medicine.drug_class ,Syngeneic tumor ,Transfection ,Biology ,Pharmacology ,Acquired immune system ,Oncology ,Trastuzumab ,ErbB ,Cancer research ,medicine ,medicine.drug - Abstract
Antibodies against cancer-relevant targets can recruit Fc receptor-bearing myeloid and natural killer cells to mediate antibody dependent cellular cytotoxicity (ADCC). Toll-like receptors are potent activators of the innate immune system and generate signals leading to the initiation of an adaptive immune response that can be utilized for therapeutic purposes. We tested the efficacy of E6020, a TLR4 agonist, administered in combination with the clinically approved anti-HER2 antibody trastuzumab. A four-week course of therapy with trastuzumab and E6020 protected against the outgrowth of syngeneic D5 melanoma cells transfected with the human tumor antigen HER2 in immunodeficient C57BL/6 SCID mice, in immunocompetent wild-type C57BL/6 mice as well as in human HER2-tolerant C57BL/6 hmHER2 transgenic mice. In each tested strain of mice, the addition of E6020 to trastuzumab significantly increased the proportion of animals that survived initial tumor challenge compared to trastuzumab treatment alone (83% vs. 33% in C57BL/6 hmHER2 transgenic mice; p < 0.05). To determine if apparently cured mice had been effectively immunized against human HER2, the transgenic mice were inoculated subcutaneously with 103 D5-HER2 cells and then received a 4-week course of trastuzumab+E6020, or trastuzumab alone. Animals that survived the primary tumor challenge were followed for at least 120 days and then rechallenged with 5 × 103 D5-HER2 or unmodified D5 cells and followed for a minimum of 60 additional days. Mice that had been initially treated with the combination of trastuzumab and E6020 demonstrated superior protection (22/30; 73%) to those treated with trastuzumab alone (16/36; 44%; p < 0.05) against rechallenge with D5-HER2, but no protection was seen against D5 challenge. Both CD4 and CD8 T-cells were required for full protection against rechallenge. These findings suggest that trastuzumab therapy can induce a host-protective adaptive immune response. Moreover, combined treatment with trastuzumab and a TLR4 agonist enhances both the direct anti-tumor effects of trastuzumab and a host-protective human HER2-directed adaptive immune response. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-324.
- Published
- 2010
17. Effects of in vivo depletion of immunocyte populations on herpes simplex virus glycoprotein D vaccine-induced resistance to HSV2 challenge
- Author
-
Eric M. Mishkin, Maria Blasiak, David P. Giorgio, and Sally T. Ishizaka
- Subjects
Cellular immunity ,viruses ,T-Lymphocytes ,Immunology ,Herpesvirus Vaccines ,Biology ,medicine.disease_cause ,Antibodies, Viral ,Lymphocyte Activation ,Virus ,Herpesviridae ,Microbiology ,Mice ,In vivo ,Virology ,Alphaherpesvirinae ,medicine ,Animals ,Simplexvirus ,chemistry.chemical_classification ,Immunosuppression Therapy ,Mice, Inbred BALB C ,Vaccination ,Herpes Simplex ,Viral Vaccines ,biology.organism_classification ,Lymphocyte Subsets ,Herpes simplex virus ,chemistry ,Humoral immunity ,Molecular Medicine ,Female ,Glycoprotein - Abstract
BALB/c mice, preimmunized with a protective dose of native herpes simplex virus type 1 glycoprotein D (ngD1) vaccine, were depleted of selected immunocyte populations in vivo using monoclonal antibodies directed at Thy1+, L3T4+, or Lyt2+ cells. Following immunization and depletion, animals were inoculated with varied challenge levels of herpes simplex virus type 2 (HSV2) in the footpad and were monitored for disease. Both depleted undepleted gD-immunized mice were significantly protected when compared with placebo controls. T-cell-independent protection in Thy1 and L3T4-depleted ngD1-immunized animals was effective at low and moderate levels of HSV2 challenge levels, high levels of HSV2 giving high symptom scores in immunized and depleted mice. Depletion of Lyt2+ cells had no significant effect on the outcome of HSV2 infection. Depleted and nondepleted animals also were assessed in parallel for cellular and humoral responsiveness to ngD1 and to HSV antigens in vitro. Lymphoproliferative responses were abrogated in gD-immunized mice treated with anti-Thy1 or anti-L3T4, anti-Lyt2 treatment having little effect. Postimmunization T-cell depletion did not undermine ELISA or neutralizing antibody responses. These findings suggest that at low to moderate levels of virus challenge vaccine-elicited antibody plays a primary role in limiting the severity of infection, T-cell-mediated protective responses being of enhanced significance only at high levels of virus challenge.
- Published
- 1992
18. Native HSV glycoprotein D subunit vaccine: analysis of in vitro T-cell activation and antigen presentation
- Author
-
E.M. Mishkin and Sally T. Ishizaka
- Subjects
Cellular immunity ,T cell ,T-Lymphocytes ,Immunology ,Antigen presentation ,Guinea Pigs ,Herpesvirus Vaccines ,Biology ,medicine.disease_cause ,Lymphocyte Activation ,Virus ,Mice ,Immune system ,Antigen ,Viral Envelope Proteins ,Virology ,medicine ,Splenocyte ,Animals ,Simplexvirus ,Mice, Inbred BALB C ,Vaccines, Synthetic ,Macrophages ,Histocompatibility Antigens Class II ,Herpes Simplex ,Viral Vaccines ,medicine.anatomical_structure ,Herpes simplex virus ,Molecular Medicine - Abstract
Native herpes simplex virus (HSV) glycoprotein D (ngD1) subunit vaccine, a potential human vaccine candidate, was examined to determine responsive murine lymphocyte populations in vitro. This vaccine preparation has been shown to protect against HSV challenge in mice and guinea pigs and to elicit humoral and cellular responses in rodents and primates. Immunized BALB/c mice were used in splenocyte lymphoproliferative studies to analyze the cellular response. After in vivo sensitization, the in vitro proliferative response observed appears to be resultant of Class II-restricted T-cell division in response to gD presented in the context of macrophage-expressed Ia.
- Published
- 1991
19. Ontogeny of T-cell function: Alloreactivity appears earlier than reactivity against hapten-modified self and interleukin-2 production
- Author
-
Sally T. Ishizaka and Osias Stutman
- Subjects
Cytotoxicity, Immunologic ,Interleukin 2 ,Aging ,T-Lymphocytes ,T cell ,Immunology ,chemical and pharmacologic phenomena ,Stimulation ,Biology ,T-Lymphocytes, Regulatory ,Pathology and Forensic Medicine ,Mice ,Species Specificity ,Antigen ,medicine ,Animals ,Antigens, Ly ,Immunology and Allergy ,Cytotoxic T cell ,Sensitization ,Lymphokines ,Mice, Inbred C3H ,In vitro ,Mice, Inbred C57BL ,CTL ,medicine.anatomical_structure ,Animals, Newborn ,Trinitrobenzenes ,Mice, Inbred CBA ,Interleukin-2 ,Haptens ,Spleen ,medicine.drug - Abstract
The capacity to generate cytotoxic T cells (CTL) against allogeneic or hapten-modified syngeneic cells after in vitro sensitization was studied in C57BL/6J and CBA/H mice of different ages, beginning at 5 days of age. A differential maturation rate for allogeneic versus hapten-modified syngeneic CTL reactivity was observed in both strains, with alloreactivity appearing earlier than reactivity to hapten-modified self antigens. For example, in C57BL/6J mice, alloreactive CTLs were detected within the first week of life, reaching adult levels by the second-third week, while the response to modified-self appeared at the secon-third week and reached adult levels by the fourth-fifth week of life. Cross-reactive lysis of hapten-modified allogeneic targets followed the same maturation pattern as the modified-syngeneic response. The low CTL reactivity of 6-day-old spleens was not due to suppressor cells. Mixing Lyt-2− (Lyt-1+) and Lyt-2+ cells from 6-day-old and adult spleens showed that the main defect was in the T helper compartment. In addition, the capacity to produce interleukin-2 (IL-2) after mitogen or allogeneic stimulation was also defective in the young mice, appearing approximately by the second week of life and reaching adult levels by the fourth-fifth week. The IL-2-deficient production was the result of both T-cell immaturity (or low numbers) as well as macrophage-accessory cell deficiency. In summary, the inefficiency of CTL generation early during the postnatal development is complex and cannot be attributed to deficiencies of a single component. The present studies, however, cannot explain the reason for the earlier appearance of alloreactivity in ontogeny.
- Published
- 1982
20. Analysis by limiting dilution of interleukin 2-producing T cells in murine ontogeny
- Author
-
Osias Stutman and Sally T. Ishizaka
- Subjects
Interleukin 2 ,Aging ,medicine.medical_specialty ,T-Lymphocytes ,Ontogeny ,Immunology ,Cell Count ,Stimulation ,Spleen ,Lymphocyte Activation ,Mice ,Internal medicine ,Immune Tolerance ,medicine ,Animals ,Immunology and Allergy ,Lymph node ,Cells, Cultured ,biology ,Stem Cells ,Lymphokine ,Cell Differentiation ,T lymphocyte ,medicine.anatomical_structure ,Endocrinology ,Concanavalin A ,Mice, Inbred CBA ,biology.protein ,Interleukin-2 ,medicine.drug - Abstract
The ontogeny of interleukin 2 (IL 2) production in young CBA/HT6T6J mice was studied using both bulk culture and limiting dilution methods. The ability of spleen cells in bulk culture to produce IL 2 in response to concanavalin A (Con A) was found to rise through the first 2 weeks of life, from no production at day 1, through 20 units/ml at day 6, to 80-100 units/ml in adults. No evidence for suppression of IL 2 production by young spleen was found. Limiting dilution analysis of both young spleen and young lymph node (LN) shows that young spleen has a much lower complement of cells producing IL 2 in response to Con A or allogeneic stimulation than does adult spleen. The frequency of 6-day spleen cells producing IL 2 in response to Con A is 1/1000, while the adult frequency is approximately 1/50. Young LN, in contrast, has levels of IL 2-producing cells close to those of adult LN, with a frequency of responders to Con A of 1/20. No evidence was found for a deficiency in IL 2 production on a per cell basis, in either 6-day spleen or LN. In examining allogeneic reactivity, a high frequency of cells reacting to strong Mls stimulation was found in both young and adult spleen and LN.
- Published
- 1983
21. Contributors
- Author
-
Jochen Abb, Toru Abo, Raffaella Acero, Hans Acha-Orbea, Dolph O. Adams, William H. Adler, Lars Ährlund-Richter, Anders Ahre, Saverio Alberti, Jane E. Allan, Paola Allavena, Anthony C. Allison, Abdulrazzak Alsheikhly, D. Bernard Amos, Torbjörn Andersson, G. Andrighetto, Tadao Aoki, Yoshitaka Aoyagi, Shmuel Argov, Inger Axberg, Fritz H. Bach, Jean-Francois Bach, Malcolm G. Baines, Tibor Bakács, Charles M. Balch, Pierre Bardos, Teresa Barlozzari, Scott P. Bartlett, Jerry A. Bash, Thomas Bechtold, Dean Befus, Maria T. Bejarano, Miklós Benczur, Michael Bennett, Miroslav Beran, E. William Bere, Kurt Berg, Peter Biberfeldt, John Bienenstock, Andrea Biondi, Christine A. Biron, Katleen Bizière, Henric Blomgren, Barry R. Bloom, Eda T. Bloom, Richard S. Bockman, Reinder Bolhuis, Benjamin Bonavida, G. D Bonnard, Diana Boraschi, Claudio Bordignon, Barbara Bottazzi, Philippe Bougnoux, Thomas P. Bradley, C. Phillip Brandt, Colin G. Brooks, Garth W. Brown, Michael J. Brunda, D. Brunet, Donald E. Burgess, Robert C. Burton, Jean Caraux, George A. Carlson, Olli Carpén, Robin Carpenter, Giorgio Caspani, Y. Cayre, C. Cesarmi, Kenneth S.S. Chang, Zong-liang Chang, Christina Cheers, Donna A. Chow, Tae June Chung, James A. Clagett, Edward A. Clark, Alistair J. Cochran, C. Colmenares, Nicoletta Colombo, Max D. Cooper, Susanna Cunningham-Rundles, Didier Cupissol, Michael Cuttito, Paula J. D’Amore, Surjit K. Datta, Jan E. de Vries, J. H Dean, Danielle Degenne, Friedrich Deinhardt, Alfred C. Denn, Gunther Dennert, James J. Devlin, David Dexter, Julie Y. Djeu, Marie-Christine Dokhélar, Wolfgang Domzig, Maria Benedetta Donati, Jean-Marie Dupuy, Anne Edwards, Margalit Efrati, Rachel Ehrlich, Anneka Ehrnst, Stefan Einhorn, Jørgen Ellegaard, Sandra L. Emmons, Helmut Engler, Elsie M. Eugui, Isrván Földes, Astrid Fagraeus, Virginia Fanning, Carine Favier, François Favier, Mei-fu Feng, Gabriel Fernandes, Manlio Ferrarini, Helmut Feucht, Carl G. Figdor, Dina G. Fischer, Patricia Fitzgerald, James T. Forbes, Adrien Forget, Bertil Fredholm, Cecilia Galatiuc, Michael T. Gallagher, Tamás Garam, Maria Gherman, Pietro Ghezzi, Magnus Gidlund, Steven Gillis, Ronald H. Goldfarb, Marc G. Golightly, Sidney Golub, Robert A. Good, E. Gorelik, Donald L. Granger, Gale A. Granger, Arthur I. Grayzel, F. Anthony Greco, Arnold H. Greenberg, Alvar Grimberg, Philippe Gros, Peter Groscurth, Carlo Enrico Grossi, Zvi Grossman, Jane E. Grundy (Chalmer), Sudhir Gupta, Éva Gyódi, Bengt Härfast, Sonoko Habu, Tina Haliotis, Nabil Hanna, Mona Hansson, Andrew J. Hapel, Frank Hatcher, Toshio Hattori, A. Hatzfeld, Sven Haukaas, Barton F. Haynes, Steven H. Hefeneider, Stephen Helfand, Hans Hengartner, Christopher S. Henney, R. B Herberman, Iver Heron, Peter Hersey, John B. Hibbs, Thomas Hoffman, Marianne Hokland, Peter Hokland, Howard T. Holden, Susan R. Hollán, E. Carmack Holmes, Yon Horikawa, Dorothy Hudig, Nam Doll Huh, James N. Ihle, Martino Introna, Sally T. Ishizaka, Teruko Ishizaka, T. Jablonski, Pamela J. Jensen, Bo Johansson, Donald R. Johnson, William J. Johnson, Mikael Jondal, Klas Kärre, Dominique Kaiserlian, Terje Kalland, Masataka Kasai, Peter Kaudewitz, Ichiro Kawase, Norihiko Kawate, Eli Kedar, Robert Keller, Rolf Kiessling, Yoon Berm Kim, Holger Kirchner, Dahlia Kirkpatrick, Eva Klein, George Klein, Gunnar O. Klein, Eugenie S. Kleinerman, Jean Pierre Kolb, Patricia A.L. Kongshavn, G. C Koo, Hillel S. Koren, Dietrich Kraft, Richard Kubota, Raymond E. Kuhn, Vinay Kumar, Patrick C. Kung, Takanobu Kurashige, Kagemasa Kuribayashi, Nuha T. Kusaimi, Santo Landolfo, Fred Lanefeldt, Rosmarie Lang, Emanuela Lanza, Tamás Laskay, Edmund C. Lattime, Gad Lavie, Jeffrey A. Ledbetter, Kam H. Leung, Elinor M. Levy, Tullia Lindsten, Marc Lipinski, Marie-Luise Lohmann-Matthes, Jürgen Lohmeyer, Bernard Longhi, Carlos Lopez, Eva Lotzová, Anne Luck, Walter Luini, John A. Lust, Jenny Macgeorge, Elinor Malatzky, Annette E. Maluish, Moiara Manciulea, Rosemonde Mandeville, Alberto Mantovani, R. J Marchmont, Pancrazio Martinetto, Giovanna Martinotti, Giuseppe Masucci, Maria G. Masucci, Aoi Masuda, S. Matzku, William McCarthy, D. Olga McDaniel, Ronald C. McGarry, P. F Mellen, Håkan Mellstedt, Jean E. Merrill, Michael Micksche, Aaron E. Miller, V. Miller, Gerald Milton, Nagahiro Minato, Karen M. Miner, Lory Minning, L. R Mittl, Hideo Miyakoshi, Mikio Mizukoshi, Pierangela Molina, M. Moore, Doris Morgan, Andrew V. Muchmore, Edwin D. Murphy, Juneann Murphy, Kenneth E. Muse, Mircea Musset, Anthony G. Nasrallah, John R. Neefe, P. Andrew Neighbour, Walter Newman, Masayuki Niitsuma, Kennith Nilsson, Erling Norrby, Masato Nose, Gerhard Obexer, Thomas N. Oeltmann, Ko Okumura, Susana Olabuenaga, Claes Örvell, John R. Ortaldo, György Pálffy, Gerd R. Pape, Elena Pasqualetto, Manuel Patarroyo, Gene A. Pecoraro, Louis M. Peius, J. R Peppard, Giuseppe Peri, Peter Perlmann, Bice Perussia, Sidney Pestka, Győső Petrányi, Gerald E. Piontek, Chris D. Platsoucas, B. Pohajdak, Nadia Polentarutti, Sylvia B. Pollack, Nicholas M. Ponzio, Elizabeth L. Priest, Hugh Pross, Tamás Pulay, David T. Purtillo, Robert S. Pyle, Phuc-Canh Quan, Keith M. Ramsey, Doug Redelman, Robert Rees, Elizabeth Reinitz, Gérard Renoux, Micheline Renoux, Augustin Rey, Craig W. Reynolds, Carlo Riccardi, Ernst Peter Rieber, Gert Riethmüller, Gábor Ringwald, Normand Rocheleau, John C. Roder, B. Rosen, Kendall L. Rosenthal, John B. Roths, Domenico Rotilio, Berish Y. Rubin, Peter Rubin, Mary J. Ruebush, Helmut Rumpold, Eero Saksela, Mario Salmona, Angela Santoni, C. A Savary, Queen B. Saxena, Rajiv K. Saxena, Liesel Schindler, Günter Schlimok, Hans Schreiber, Janet K. Seeley, Anna Senik, Susana A. Serrate, Bernard Serrou, Susan O. Sharrow, Geoffrey R. Shellam, Akira Shibata, Kazuo Shimamura, Frederick P. Siegal, Emil Skamene, Scott D. Somers, Hergen Spits, Ivana Stoger, Beda M. Stadler, Mary M. Stevenson, Lothar Stitz, Hans Strander, Osias Stutman, Andrei Sulica, Deming Sun, Egon Svastits, Aldo Tagliabue, Mitsuo Takasugi, Margarita Tálas, Kenichi Tanaka, Donatella Taramelli, Stephan R. Targan, Jussi Tarkkanen, Eckardt Thiel, Tuomo Timonen, Klára Tótpál, Thomas Tötterman, John J. Trentin, Giorgio Trinchieri, Thomas Tursz, Atsushi Uchida, Mans Ullberg, James Urban, David L. Urdal, Farkas Vánky, Luigi Varesio, Miklòs Varga, Ismo Virtanen, B. M Vose, Jerrold M. Ward, James E. Weiel, William O. Weigle, Monica L. Weitzen, Raymond M. Welsh, Jerome A. Werkmeister, Patricia A. Weston, H. Wigzell, R. Wiltrout, Nancy T. Windsor, Henry J. Winn, Isaac P. Witz, James N. Woody, Susan C. Wright, Robert S. Yamamoto, Ganesa Yogeeswaran, M. Zöller, Daniel Zagury, Helmut Zander, Joyce M. Zarling, Rainer Zawatzky, and Hans-Werner Loems Ziegler
- Published
- 1982
22. NC CELLS DO NOT EXPRESS NK-ASSOCIATED CELL SURFACE ANTIGENS AND ARE NOT CULTURE ACTIVATED NK CELLS
- Author
-
Edmund C. Lattime, Osias Stutman, Sally T. Ishizaka, Gene A. Pecoraro, and Gloria C. Koo
- Subjects
Antiserum ,Interleukin 21 ,medicine.anatomical_structure ,Lymphokine-activated killer cell ,Glycolipid ,Antigen ,Cell ,medicine ,Cytotoxic T cell ,Cell Surface Antigens ,Biology ,Cell biology - Abstract
Publisher Summary This chapter discusses the difference between natural cytotoxic (NC) cell activity and natural killer (NK) cell activity. The studies described in this chapter address two questions: (1) do NK and NC cells express similar cell surface antigens and (2) if not, can differential antigen expression allow the separation of NK and NC functions and, thus, facilitate studies into the relationship of the two populations. NK cells have been shown to share a number of cell surface antigens with other lymphoid populations. NK cells express the T-cell associated Qa-2,3, Qa-5, and Ly-11 antigens. NK cells bear the neutral glycolipid asialo GM-1, NK 1.1, and NK 1.2 antigens and have been shown to express high levels of H-2. Studies described in the chapter demonstrate that NK and NC cells markedly differ in antigen expression. NC cell activity is not affected by treatment with antisera directed to the Qa-2,3, Qa-5, Ly-11, NK 1.2, or asialo GM-1 antigens, all of which deplete NK cell activity. The results also suggest that the NC cell is low in H-2 expression.
- Published
- 1982
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.