bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-human IgG causes basophil histamine release by acting on IgG-IgE complexes bound to IgE receptors.
Authors: Lichtenstein L M , Kagey-Sobotka A , White J M , Hamilton R G 
Published: December 2022

Abstract
We have reexamined the ability of anti-human IgG antibodies to induce histamine release from human basophils. A panel of purified murine mAbs with International Union of Immunological Societies-documented specificity for each of the four subclasses of human IgG was used. Of the 24 allergic subjects studied, the basophils of 75% (18/24) released greater than 10% histamine to one or more anti-IgG1-4 mAb, whereas none of the 13 nonatopic donor's basophils released histamine after stimulation with optimal amounts of anti-IgG mAb. The basophils of 85% (11/13) of the nonatopic donors did respond to anti-IgE challenge, as did 92% (22/24) of the atopic donor cells. Histamine release was induced most frequently by anti-IgG3, and 10/18 anti-IgG responder cells released histamine with mAb specific for two or more different subclass specificities. The rank order for induction of histamine release was anti-IgG3 greater than anti-IgG2 greater than IgG1 greater than anti-IgG4. As in our previous study using polyclonal anti-IgG, 100- to 300-micrograms/ml quantities of the anti-IgG mAb were required for maximal histamine release, about 1000-fold higher than those for comparable release with anti-human IgE. Specificity studies using both immunoassays and inhibition studies with IgE myeloma protein indicated that anti-IgG induced histamine release was not caused by cross-reactivity with IgE. Ig receptors were opened by lactic acid treatment so that the cells could be passively sensitized. Neither IgE myeloma nor IgG myeloma (up to 15 mg/ml) proteins could restore the response to anti-IgG mAb. However, sera from individuals with leukocytes that released histamine upon challenge with anti-IgG mAb could passively sensitize acid-treated leukocytes from both anti-IgG responder and nonresponder donors for an anti-IgG response. The only anti-IgG mAb that induced release from these passively sensitized cells were those to which the serum donor was responsive. Sera from non-IgG responders could not restore an anti-IgG response. These data led to the hypothesis that the IgG specific mAb were binding to IgG-IgE complexes that were attached to the basophil through IgE bound to the IgE receptor. This was shown to be correct because passive sensitization to anti-IgG could be blocked by previous exposure of the basophils to IgE. We conclude that anti-IgG-induced release occurs as a result of binding to IgG anti-IgE antibodies and cross-linking of the IgE receptors on basophils.
A universal T cell epitope-containing peptide from hepatitis B surface antigen can enhance antibody specific for HIV gp120.
Authors: Greenstein J L , Schad V C , Goodwin W H , Brauer A B , Bollinger B K , Chin R D , Kuo M C 
Published: December 2022

Abstract
Peptide-based vaccines that directly target T cell or B cell epitopes may have significant advantages over conventional vaccines. Further, synthetic chimeric peptides that combine strong T cell epitopes with poorly immunogenic, but immunodominant, B cell epitopes or strain-conserved B cell epitopes may be useful in eliciting antibody to such important regions. Here we characterize a human T cell epitope analyzed in 54 individuals immunized with a hepatitis B virus surface Ag vaccine. Primary cultures from a total of 59 immunized donors were assessed for their ability to respond to hepatitis B virus surface Ag and peptides, and five were non-responders (8.5%). T cell lines were established from the remaining 54 responders. Of the responders, it was found that the peptide representing amino acids 19 through 33 (19-33) elicited significant proliferation in lines derived from 50 donors. This "universal" T cell epitope, which was recognized in donors of many different HLA-DR and -DQ haplotypes, was then used to construct a chimeric peptide containing 19-33 and the third V region loop structure (V3 loop) of HIV-1 envelope gp 120, in an attempt to augment the immune response to the V3 loop peptide. The V3 loop is the region to which significant neutralizing antibody is directed. Thus, a strong immune response to a synthetic peptide that contains the strain-conserved V3 loop region could have significant therapeutic implications. The V3 loop/19-33 peptide was then used to prime mice, to determine whether V3 loop-specific antibody could be induced. The peptide elicited potent 19-33-specific proliferation in T cells isolated from draining lymph nodes, and in six of six mice anti-V3 loop antibody was elicited. Further, V3 loop/19-33-primed animals made significant levels of antibody that bound rgp120. These data suggest that, when a major T cell epitope is synthesized in tandem with the V3 loop, a significant immune response against the loop can be elicited. Thus, given the finding that neutralizing antibody may play a role in the control and/or prevention of HIV infection, an HIV vaccine composed of a T cell epitope-containing peptide may prove effective. In addition, this type of approach can be generalized to the design of peptide-based vaccines.
A synthetic peptide spontaneously self-assembles to reconstruct a group-specific, conformational determinant of hepatitis B surface antigen.
Authors: Manivel V , Ramesh R , Panda S K , Rao K V 
Published: December 2022

Abstract
A cysteine-rich peptide of sequence 124 to 147 of the major protein of hepatitis B surface Ag (HBsAg) was synthesized. On cleavage and subsequent work-up it was found that all of the cysteine sulfhydryl groups had spontaneously formed disulfide bonds to yield a heterogenous mixture of multiple forms with molecular masses ranging from 8 to 35 kDa (peptide OS[124-147]). In a direct ELISA peptide OS[124-147] showed a high degree of cross-reactivity with polyclonal anti-HBsAg antiserum whereas the HBsAg-related antigenicity of its disulfide-reduced analogs was insignificant. Peptide OS[124-147] was also recognized by all 15 of the anti-HBsAg-positive human sera tested. Further studies revealed that peptide OS[124-147] represents the conformational, disulfide-dependent "a" determinant of HBsAg and elicits antibodies that cross-react with a variety of HBsAg subtypes. Anti-peptide antibodies bound to the corresponding native epitope with an apparent affinity higher than that of homologous antisera. Finally, polyclonal anti-OS[124-147] antibodies could also immunoprecipitate purified Dane particles in solution. Together these studies indicate that peptide OS[124-147] represents an excellent candidate component of a peptide-based vaccine for hepatitis B.
Tumor necrosis factor induces genes involved in inflammation, cellular and tissue repair, and metabolism in murine fibroblasts.
Authors: Gordon H M , Kucera G , Salvo R , Boss J M 
Published: December 2022

Abstract
TNF-alpha is a primary mediator of the inflammatory response and has been ascribed a wide range of biologic activities including the cytolysis of some but not all transformed cell lines in vitro. Since most cells, normal and transformed, will also be lysed if they are concurrently treated with inhibitors of transcription or translation, the ability to resist TNF lysis depends on the de novo induction of specific gene products. To identify genes that might be involved in the ability to resist TNF-mediated cytolysis, cDNA libraries enriched for TNF-induced genes were constructed and screened. Twenty-one genes that are induced by TNF were isolated. Ten of the cDNA clones were identified by DNA sequence analysis and function in inflammatory responses, tissue or cellular repair, or cellular metabolism. Seven genes were not identified and are novel. The remaining four genes are encoded in the mitochondrial genome. Interestingly, not all the mitochondrial transcripts are induced. This may reflect a fine tuning of certain components of mitochondria that may be necessary for survival after TNF treatment.
CD45 alternative exon expression in murine and human CD4+ T cell subsets.
Authors: Rogers P R , Pilapil S , Hayakawa K , Romain P L , Parker D C 
Published: December 2022

Abstract
Leukocytes express a family of high m.w. glycoproteins called leukocyte common Ag (CD45), which are involved in phosphotyrosine signal transduction. Antibodies to different CD45 isoforms distinguish functionally different CD4+ T cell subsets in humans, rats, and mice. Selected protein isoforms are expressed through a process of exon splicing that is cell-type and differentiation-state specific. Splicing of the three variable exons, A, B, and C, which encode amino acids located near the extracellular amino terminus of the protein, potentially results in generation of eight different mRNA transcripts. The purpose of the present study was to determine the relative levels of all eight different CD45 transcripts present in a panel of murine CD4+ T cell lines and normal murine and human CD4+ T cell subsets separated with antibodies to CD45 variable exons. We show, as expected, that the broad features of CD45 surface isoform expression in these cells can be accounted for by the relative amounts of the eight differentially spliced transcripts. Unexpectedly, all the differences in CD45 isoform expression among the CD4+ T cell subpopulations that we measured could be accounted for by differences in the overall level of variable exon expression. We did not see differences among T cell populations in the relative expression of particular variable exons. Exon B was always found in greater abundance than exons C or A. Of the dual exon species, only AB and BC were found in CD4+ T cells. The AC species was undetectable. Human CD4+ T cells, especially those in the naive subset, express higher levels of CD45 variable exons than murine CD4+ T cells.
A "network antigen" for human CD4. A murine monoclonal anti-idiotype to Leu-3a induces an anti-CD4 response in naive mice.
Authors: Healey D G , Dianda L , Beverley P C 
Published: December 2022

Abstract
Previous studies have evaluated anti-CD4 mAb as idiotypic models of the HIV gp120-binding site for CD4. The success of this strategy depends upon the concept of internal image, whereby the binding paratope of the anti-CD4 structurally mimics the equivalent binding surface on HIV gp120. To test this concept of internal image, anti-idiotypic antibodies were raised against the anti-CD4, Leu-3a. If any of these anti-Id detect the paratopic idiotope on the anti-CD4 antibody, their own respective paratopes should structurally model the corresponding binding epitope on CD4 bound by Leu-3a. Consequently, the immunization of naive mice with the selected anti-Id should induce an anti-CD4 response which reflects the binding specificities of Leu-3a. Four anti-Id to Leu-3a were characterized and tested for their ability to induce anti-CD4 responses in naive animals. Although one anti-Id induced an anti-CD4 response in mice, no such response could be detected in other species. Thus the failure to raise anti-Id with internal image characteristics may provide an explanation for the lack of anti-gp120 activity reported in anti-Id antisera raised to multiple anti-CD4 antibodies.
Virus-induced loss of class I MHC antigens from the surface of cells infected with myxoma virus and malignant rabbit fibroma virus.
Authors: Boshkov L K , Macen J L , McFadden G 
Published: December 2022

Abstract
Shope fibroma virus (SFV) is a leporipoxvirus that causes localized benign fibromas in immunocompetent adult rabbits that spontaneously regress due, in part, to a cell-mediated immune response. Myxoma virus (MYX) and malignant rabbit fibroma virus (MRV) are related leporipoxviruses that induce rapidly lethal generalized infections accompanied by tumors and immunosuppression. Because only these latter two viruses are known to compromise cell-mediated antiviral responses, cell surface levels of class I MHC molecules in SFV-, MRV-, and MYX-infected cells were investigated by fluorescent activated cell sorting analysis using a variety of different anti-HLA mAb. After infection with MYX or MRV there is a rapid decrease in the levels of detectable surface class I epitopes as detected by each antibody and by 24 h postinfection class I MHC Ag levels at the cell surface approach the level of background fluorescence observed with control antibodies. In contrast, only a moderate class I decrease is seen during infection with either SFV or vaccinia virus, an orthopoxvirus that is neither tumorigenic nor immunosuppressive. Surface class I marker loss induced by MYX and MRV is not simply due to nonspecific inhibition of total cellular protein synthesis by the viruses because class I levels decrease much further than the extent measured by estimating surface marker turnover in the presence of the protein synthesis inhibitor cycloheximide. Thus the loss of cellular surface class I molecules greatly exceeds the drop in level caused by complete blockage of host cell gene expression, and must involve removal or masking of preexisting class I epitopes from the cell surface by MRV/MYX. Cell surface levels of the transferrin receptor are unaffected by MYX and MRV infection, suggesting the observed class I decrease is not a nonspecific effect on total cell surface glycoproteins. Analysis of cells infected with MRV/MYX in the presence of cycloheximide or of cytosine arabinoside, an inhibitor of poxviral DNA replication, indicates that the class I marker loss is mediated in part by one or more viral late gene products. A probable explanation is that MRV/MYX late protein(s) interact with the class I MHC complex to either physically sequester these away from the cell surface and inhibit their recycling or else induce a conformational change that precludes recognition by all class I antibodies tested. In either event, we propose that such a major perturbation of the class I MHC complex would likely downregulate the class I-mediated presentation of viral Ag required to initiate cell-mediated immunity to these viruses.
Overlapping epitopes that are recognized by CD8+ HLA class I-restricted and CD4+ class II-restricted cytotoxic T lymphocytes are contained within an influenza nucleoprotein peptide.
Authors: Carreno B M , Turner R V , Biddison W E , Coligan J E 
Published: December 2022

Abstract
Viral epitopes that are recognized by both HLA class I-restricted and class II-restricted T cells have been defined for a type A influenza virus nucleoprotein (NP) peptide. CD8+ and CD4+ CTL lines have been generated against a synthetic peptide encompassing residues 335 to 349 of NP that are restricted by HLA-B37 and HLA-DQw5, respectively. Both of these CTL populations were capable of specifically lysing influenza A virus-infected targets, indicating that a naturally processed NP peptide(s) was being mimicked by the NP (335-349) peptide. Amino acid residues that are critical for recognition of this NP determinant in the context of HLA-B37 and HLA-DQw5 were investigated by the use of panels of truncated and alanine-substituted NP peptides. The results demonstrate that: 1) truncations in the amino- or carboxy-terminal ends differentially affect CD8+ and CD4+ CTL recognition; 2) the NP (335-349) sequence contains two octapeptide epitopes that share a core of six amino acid residues (NP 338-343); and 3) alanine substitutions at five of these residues abrogated recognition by at least one of the CD8+ and CD4+ CTL lines. Thus, these class I- and class II-restricted CTL lines recognize similar but distinct epitopes, and different structural features of the NP peptide are required for presentation by HLA-B37 and HLA-DQw5. Comparison of the amino acid sequences of the NP peptide presented by HLA-B37 and HLA-DQw5 with other peptides known to be presented by both class I and class II molecules revealed a common motif among these peptides.
Role of IL-4 and IFN-gamma in Schistosoma mansoni egg-induced hypersensitivity granuloma formation. Orchestration, relative contribution, and relationship to macrophage function.
Authors: Chensue S W , Terebuh P D , Warmington K S , Hershey S D , Evanoff H L , Kunkel S L , Higashi G I 
Published: December 2022

Abstract
A well defined model of T cell-mediated hypersensitivity-type granulomatous inflammation induced by Schistosoma mansoni eggs was used to assess the role of IL-4 and IFN-gamma in granuloma development. Synchronized pulmonary granulomas were induced and isolated from S. mansoni-infected mice during vigorous (8 wk) and modulated (20 wk) stages of the disease. The sequential production of IL-4 and IFN was determined and related to temporal changes in granuloma macrophage production of IL-1, TNF, and superoxide anion (O2-). During the vigorous stage, IL-4 was produced on days 1 and 2 of granuloma formation, whereas IFN was released in greatest amounts on days 4 to 8. The peak of IL-4 occurred in a window between the peak of IL-1 (1 day) and maximal TNF production (8 to 16 days). Maximal O2- release tended to parallel IFN production. During the modulated stage when the inflammatory response is attenuated, IL-4 production was dramatically reduced as were levels of IL-1 and TNF, but IFN production persisted and maximum O2(-)-producing capacity was only delayed in onset. mAb specific for IL-4 and IFN were used to examine the effect of in vivo depletion of these cytokines on granuloma development. Administration of a single 1.0-mg dose of anti-IL-4 antibodies to mice with synchronously developing granulomas dramatically reduced granuloma size (40 to 50% suppression of area) during an 8-day study period, whereas antibodies to IFN had no effect on size. However, the latter treatment reduced giant cell formation. Our results indicate that granuloma development involves an orchestrated production of cytokines possibly resulting from sequential participation of different Th cell populations. Moreover, IL-4 is a pivotal cytokine in anamnestic cellular recruitment and subject to endogenous regulation.
Human peripheral blood lymphocytes transplanted into SCID mice constitute an in vivo culture system exhibiting several parameters found in a normal humoral immune response and are a source of immunocytes for the production of human monoclonal antibodies.
Authors: Carlsson R , Mårtensson C , Kalliomäki S , Ohlin M , Borrebaeck C A 
Published: December 2022

Abstract
Human PBL from vaccinated healthy blood donors, which was transplanted i.p. into mice with severe combined immunodeficiency (SCID), exhibited an Ag-dependent humoral Ir against tetanus toxoid. This Ir was dose dependent and was completely abrogated by immunizing with large amounts of Ag, suggesting a high dose tolerization of the B cells. A dose-dependent selection of specific, high affinity B clonotypes was also suggested, since immunization with low concentrations of tetanus toxoid produced antisera with higher avidity than immunizations using a high dose of Ag. The production of human Ig and the clonal outgrowth of normal human B cells in the SCID mouse was strongly down-regulated by human NK cells. Human immune B lymphocytes were also recovered from immunized SCID mice and transformed with EBV, yielding lymphoblastoid cell lines producing high affinity antitetanus human IgG antibodies. These results suggest that SCID mice, repopulated with human PBL, can constitute a functional model of several parameters of a normal human humoral Ir and can provide a source of immune B cells for the production of human mAb.
IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1.
Authors: Schleimer R P , Sterbinsky S A , Kaiser J , Bickel C A , Klunk D A , Tomioka K , Newman W , Luscinskas F W , Gimbrone M A , McIntyre B W 
Published: December 2022

Abstract
The present studies were performed to explore potentially selective mechanisms of leukocyte adhesion in an attempt to understand how preferential recruitment of eosinophils and basophils might occur during allergic and other inflammatory reactions. Stimulation of human vascular endothelial cells for 24 h with IL-4 (30 to 1,000 U/ml) induced adhesion for eosinophils (up to approximately four-fold of control) and basophils (up to approximately twofold of control) but not neutrophils (less than 125% of control). Analysis of endothelial expression of adhesion molecules by flow cytometry revealed that IL-4 treatment induced vascular cell adhesion molecule-1 (VCAM-1) expression without significantly affecting the expression of other adhesion molecules, namely endothelial-leukocyte adhesion molecule-1 (ELAM-1) or intercellular adhesion molecule-1 (ICAM-1). The concentration-response curve for IL-4-induced VCAM-1 expression paralleled that for adhesion. Endothelial cells stimulated with IL-4 expressed adhesive properties for eosinophils by 3 h; the response increased steadily during a 24-h time course study. Eosinophils and basophils adhered to plates coated with a recombinant form of VCAM-1. This adhesion was blocked with antibodies to VCAM-1 but not ELAM-1. mAb directed against either VCAM-1 or VLA-4 inhibited (by approximately 75%) the binding of eosinophils and basophils to IL-4-stimulated endothelial cells. Because VLA-4 and VCAM-1 have been demonstrated to bind to each other in other adhesion systems, these results suggest that IL-4 stimulates eosinophil and basophil adhesion by inducing endothelial cell expression of VCAM-1 which binds to eosinophil and basophil VLA-4. The lack of expression of VLA-4 on neutrophils and the failure of IL-4 to stimulate neutrophil adherence support this conclusion. It is proposed that local release of IL-4 in vivo in allergic diseases or after experimental allergen challenge may partly explain the enrichment of eosinophils and basophils (vs neutrophils) observed in these situations.
Neutrophil chemotactic factors promote leukocytosis. A common mechanism for cellular recruitment from bone marrow.
Authors: Jagels M A , Hugli T E 
Published: December 2022

Abstract
We investigated cellular responses in a rabbit to i.v. administration of five established chemotactic factors (leukotriene B4 (LTB4), platelet-activating factor (PAF), C5a, N-Formyl-Met-Leu-Phe (F-MLF), and IL-8), and each exerted a characteristic effect on circulating white blood cell levels. All five factors induced a rapid and transient leukopenia. The blood was nearly devoid of circulating neutrophils 5 min after administration of each chemotactic factor. Other leukocytes were also variably depleted during the leukopenic phase, including eosinophils, basophils, monocytes, and lymphocytes. The lymphocyte numbers remained significantly depressed (approximately 30%) for as long as 3 h after administration of PAF or f-MLF. Each chemotactic factor produced a marked neutrophilia (i.e., 250-400% of baseline levels) after the initial leukopenia. Eosinophil numbers were elevated along with the neutrophil response in the C5a- and LTB4-treated animals. Basophil levels were significantly elevated only in LTB4-treated animals. The cellular response to PAF, f-MLF, and IL-8 appeared to be specific for the neutrophils. The kinetic profiles of the neutrophilia induced by PAF (10 micrograms/kg) or f-MLF (2.5 micrograms/kg) were similar, with maximal responses occurring 3 to 4 h after administration. In contrast, LTB4 (10 micrograms/kg), IL-8 (2.5 micrograms/kg), and C5a (5 micrograms/kg) induced a more rapid neutrophilia, with peak responses occurring 1 to 1.5 h after injection, and remaining elevated for 3 to 4 h. In all animals the neutrophilia was accompanied by a relative increase in the number of nonsegmented neutrophils (bands), suggesting that a major component of leukocytosis is caused by the release of bone marrow reserves. Phenidone (10 mg/kg), a dual cyclooxygenase/5-lipoxygenase inhibitor, affected neither the neutropenia nor the neutrophilia induced by C5a, f-MLF, or PAF. The protein synthesis inhibitor actinomycin D also failed to suppress neutrophil responses induced by either C5a or PAF. These results suggest that leukocytosis is a common response induced by all neutrophil chemotactic factors. Leukocytosis appears to be a direct result of the dynamic adaptive response of neutrophils to chemotactic factor stimulation without involvement of a secondary mediator system.