bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of HLA class II molecule expressions by IFN-gamma. The signal transduction mechanism in glioblastoma cell lines.
Authors: Nezu N , Ryu K , Koide Y , Yoshida T O 
Published: December 2022

Abstract
We examined the signal transduction mechanism responsible for the IFN-gamma-induced HLA class II molecule expressions on glioblastoma cell lines, T98G and A172. A series of experiments demonstrated that the activation of protein kinase C (PKC) is involved in the DR and DP molecule expressions on T98G cells. In addition to the activation of PKC, calcium influx appeared to be involved in the DR and DP molecule expressions on T98G. Northern blot analyses with actinomycin D or cycloheximide revealed that these second messengers induce the transcription of DRA and B and DPA and B genes without de novo protein synthesis. Furthermore, we examined the region of the DPB gene that is responsible for IFN-gamma-induced gene transcription by gene transfer of a series of 5' and 3' deletion mutants in which the upstream region of the DPB was linked to a reporter gene, chloramphenicol acetyltransferase. By using these deletion mutants, it appeared that the region between -152 and -126 bp contains a critical IFN-gamma-responsive element. Taken together, these results suggest that IFN-gamma activates PKC and stimulates calcium influx, resulting in the induction of transcription of DRA and B and DPA and B genes without de novo protein synthesis. In DPB gene, we speculate that preexiting protein(s) phosphorylated by PKC in the presence of Ca2+ might directly bind or indirectly interact with the region between -152 and -126 bp of the upstream sequence, leading to the induction of the transcription (possibly in concert with other nuclear protein(s) bound to the promoter sequences).
Calcium-dependent natural killer and calcium-independent natural cytotoxic activities in an IL-2-dependent killer cell line.
Authors: Richards A L , Djeu J Y 
Published: December 2022

Abstract
Using a cloned murine cell line, NKB61A2, that concomitantly exhibits both NK and natural cytotoxic (NC) activities, we investigated the biochemical mechanisms involved in natural cell mediated cytotoxicity against NK-sensitive YAC-1 tumor cells and against the NC-sensitive WEHI-164 tumor cells. Recent reports have suggested that target cell lysis by cytotoxic lymphocytes occurs by either a calcium dependent and/or a calcium-independent mechanism(s). To determine the role of calcium in NK and NC activities of the NKB61A2 cell line, we evaluated the effect of: 1) extracellular Ca2+ depletion by the divalent cation chelator, EGTA, 2) Ca2+ influx blockade by the Ca2+ channel blocker verapamil, and 3) blocking of intracellular Ca2+ mobilization by 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8). We found that EGTA, verapamil, and TMB-8 were all capable of inhibiting NK activity, but they had little effect on NC activity of the NKB61A2 cells. Using 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide which are inhibitors of protein kinase C and calmodulin respectively, we determined that protein kinase C and calmodulin do play a role in the NK activity of NKB61A2 cells. 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and N-(6-aminohexyl)-5-chloro-1-naphthalanesulfonamide, similar to Verapamil and TMB-8, had no effect on NC activity. Thus, the data indicate that the NK activity of NKB61A2 cells is calcium dependent whereas NC activity is not. These results may explain the disparate reports seen in the literature of calcium-dependent and -independent lysis of tumor cells.
Prostaglandin E2 inhibits production of Th1 lymphokines but not of Th2 lymphokines.
Authors: Betz M , Fox B S 
Published: December 2022

Abstract
PGE2 is known to inhibit IL-2 and IFN-gamma production from Th cells and is widely viewed as a general immunosuppressant. However, PGE2 was found not to inhibit IL-4 production from Th2 clones, and IL-5 production from these clones was slightly enhanced. The same results were obtained with short term T cell lines, which indicates that the lack of inhibition of IL-4 and IL-5 production by PGE2 is a general phenomenon. PGE2 functions by increasing cAMP levels through activation of adenylate cyclase. Despite its failure to inhibit lymphokine release, PGE2 was capable of increasing cAMP levels in Th2 cells, and forskolin, a direct activator of adenylate cyclase, also did not inhibit IL-4 or IL-5 production. These data indicate that the failure of PGE2 to inhibit IL-4 and IL-5 production was not due to an inability of PGE2 to induce an increase in intracellular cAMP, and suggested instead that the expression of IL-4 and IL-5 in Th2 cells is insensitive to elevated cAMP levels. When Th0 clones were examined, PGE2 was again found to differentially affect IL-2 and IL-4 production in three of five clones tested. In two additional Th0 clones, both IL-2 and IL-4 production were inhibited. These data suggest that lymphokine production may be regulated on two different levels. First, Th1- and Th2-associated lymphokines may be differentially sensitive to intracellular signals such as cAMP. Second, T cell subsets may exist, including subsets of Th0 cells, with different signaling pathways. In addition, our data suggest that PGE2 may play an important role in regulating the development of a response dominated by Th1- or Th2-associated lymphokines.
Enhanced in vivo targeting of an asymmetric bivalent hapten to double-antigen-positive mouse B cells with monoclonal antibody conjugate cocktails.
Authors: Le Doussal J M , Gautherot E , Martin M , Barbet J , Delaage M 
Published: December 2022

Abstract
In order to target specifically double-Ag-positive cells in vivo, we synthesized chemically two mAb conjugates with specificities for both an allelic murine B cell-surface Ag and for a synthetic hapten. One conjugate was designed for its specificities for I-Ek and for N-epsilon-(2,4-DNP)-amino-caproate, and the other one for its reactivity to Lyb-8.2 and to indium-diethylenetriamine pentaacetate. A radiolabeled tracer, containing both the N-epsilon-(2,4-DNP)-amino-caproate and the indium-diethylenetriamine pentaacetate haptens, was obtained by reacting diethylenetriamine pentaacetic acid dianhydride with mono-[N-epsilon-(2,4-DNP)-amino-caproyl]-tyrosyl-lysine and labeling with indium-111. Mice from various strains (CBA/N: I-Ek+, Lyb-8.2+; AKR/N: I-Ek+, Lyb-8.2-; BALB/c: I-Ek-, Lyb-8.2+; and DBA/2: I-Ek-, Lyb-8.2-) were given simultaneous i.v. injections of microgram amounts of less than anti-[N-epsilon-(2,4-DNP)-amino-caproate], anti-I-Ek greater than and of [anti-(indium-diethylene-triaminepentaacetate), anti-Lyb-8.2] antibody conjugates and picomole amounts of the tracer. As expected, specific uptake of the tracer by the spleen was observed in strains where spleen cells expressed at least one Ag (CBA/N, AKR/N, and BALB/c). Furthermore, spleen cells from the double-Ag-positive mouse strain (CBA/N), when compared with spleen cells from single-positive mouse strains, exhibited a significantly higher uptake of the bivalent hapten. This specificity for double-Ag-positive cells, it is suggested, occurs through the formation of stable complexes between both cell-surface Ag, both conjugates, and the asymmetric bivalent hapten. The use of such asymmetric bivalent haptens, together with matched (anti-hapten, anti-cell) antibody conjugates, is proposed as a general method for increasing the in vivo specificity of immunoimaging and radioimmunotherapy.
Polyclonal activation of the murine immune system by an antibody to IgD. XI. Contribution of membrane IgD cross-linking to the generation of an in vivo polyclonal antibody response.
Authors: Goroff D K , Holmes J M , Bazin H , Nisol F , Finkelman F D 
Published: December 2022

Abstract
The injection of mice with a foreign, polyclonal antibody to IgD sequentially induces: 1) activation of B cells by cross-linking of their cell membrane (m) IgD; 2) B cell processing and presentation of the bound anti-IgD antibody to T cells; 3) activation of these T cells; and 4) T-dependent stimulation of B cell differentiation into IgG1 secreting cells. To determine whether the cross-linking of B cell membrane IgD and/or the resulting B cell activation that follows contribute to the generation of the polyclonal IgG1 response, we examined the abilities of three sets of anti-delta mAb or mAb fragments to stimulate polyclonal IgG1 production. Within each set mAb were matched for species and Ig isotypic determinants, but differed in avidity for IgD or in ability to cross-link IgD. In addition, experiments were performed to determine whether the anti-delta mAb had to be foreign to the immunized mouse to stimulate an IgG1 response. Results of these experiments indicate that: 1) recognition of the injected anti-delta antibody as foreign is required for the induction of a polyclonal IgG1 response; 2) the cross-linking of B cell membrane Ig, which directly activates B cells, can contribute considerably to the generation of in vivo IgG1 production; and 3) that even relatively weak cross-linking of membrane Ig by ligands that bind it with low avidity can make this contribution.
Biochemical characterization and tissue distribution of hamster complement C1s.
Authors: Sakiyama H , Yamaguchi K , Chiba K , Nagata K , Taniyama C , Matsumoto M , Suzuki G , Tanaka T , Tomoasawa T , Yasukawa M 
Published: December 2022

Abstract
Several mAb (PG11, NG7, and ED4) against hamster complement C1s were obtained. PG11 and NG7 were shown to cross-react with human and rat C1s. By using an immunohistochemical method, we examined localization of C1s in tissues of hamsters and rats. Present results revealed a widespread yet specific staining of hamster C1s which is associated with endoderm-, mesoderm-, and neuroectoderm-derived cells. For example, chondrocyte of hyaline cartilage and surface epithelium of the stomach were strongly positive. Intestinal epithelium, muscle cells, pia mater and epithelium of the choroid plexus of the ventricle, and hepatocytes were also stained. The synthesis of hamster C1s in these organs was confirmed by RNA blot hybridization. Secretion of C1s into the culture medium was revealed by immunoblot analysis in cell lines of hepatocytes, kidney cells, and myoblasts of rat or hamster.
Anti-idiotype-induced, lipopolysaccharide-specific antibody response to Pseudomonas aeruginosa. II. Isotype and functional activity of the anti-idiotype-induced antibodies.
Authors: Schreiber J R , Nixon K L , Tosi M F , Pier G B , Patawaran M B 
Published: December 2022

Abstract
We recently developed a murine anti-idiotypic mAb that functioned as a molecular mimic of the O-specific polysaccharide side chain (Ps) of Pseudomonas aeruginosa LPS in vitro, and which induced Ps-specific antibodies in syngeneic BALB/c ByJ mice. In the current studies, we demonstrate that these anti-Id-induced, Ps-specific antibodies fix complement to the bacterial cell surface, and protect neutropenic mice from fatal P. aeruginosa sepsis. The isotypic distribution of the anti-Id-induced antibodies, however, resembles the restricted pattern (IgM and IgG3) seen after administration of purified Ps to mice. The immunogenicity and number of isotypes of Ps-specific antibody produced could be enhanced by conjugating the anti-Id to keyhole limpet hemocyanin. Finally, the anti-Id administered before immunization with purified Ps, primed BALB/c ByJ mice for production of other Ps-specific antibody isotypes (IgG1). These studies show that this anti-Id induces functional anti-Ps antibodies in syngeneic mice, and when used in conjugate form or as a priming agent before Ps immunization, yields an antibody response consistent with "T cell dependence." These immunization strategies may be useful for the induction of polysaccharide-specific antibodies in man.
Immunogenicity and protective effect against oral colonization by Streptococcus mutans of synthetic peptides of a streptococcal surface protein antigen.
Authors: Takahashi I , Okahashi N , Matsushita K , Tokuda M , Kanamoto T , Munekata E , Russell M W , Koga T 
Published: December 2022

Abstract
Streptococcus mutans is known to be a major causative organism of human dental caries. A surface protein Ag with a molecular mass of 190 kDa of S. mutans (PAc) is receiving attention as an anticaries vaccine. We have recently determined the complete nucleotide sequence of the gene for PAc. In this study, four peptides were synthesized on the basis of amino acid sequence of PAc. Among these peptides, PAc(301-319) corresponding to the alanine-rich repeating amino acid region was the most strongly bound by polyclonal murine anti-rPAc antibodies. The peptide partially inhibited the binding of polyclonal anti-rPAc antibodies to rPAc. The peptide induced the proliferation of T cells from BALB/c mice immunized with rPAc. Subcutaneous immunization with PAc(301-319) or rPAc emulsified in CFA/IFA induced high serum IgG responses to rPAc and PAc(301-319). In addition, serum IgG responses to a surface protein Ag with a molecular mass of 210 kDa of Streptococcus sobrinus were elicited in mice immunized by s.c. injection with PAc(301-319) or rPAc. Intranasal immunization with PAc(301-319) coupled to cholera toxin B subunit (CTB) or with rPAc and free CTB induced high serum IgG responses to rPAc. The immunization with PAc(301-319) coupled to CTB or rPAc and free CTB suppressed the colonization of murine teeth by S. mutans. These results suggest that intranasal immunization with the peptide or rPAc may be effective for the prevention of dental caries.
The expression of the Ig H chain repertoire in developing bone marrow B lineage cells.
Authors: Decker D J , Boyle N E , Koziol J A , Klinman N R 
Published: December 2022

Abstract
Analyses of rearranged Ig H chain V region genes of bone marrow pre-B cells demonstrate extensive sequence diversity, particularly within the third hypervariable region (HCDR3). This diversity is constrained, however, through preferential utilization of certain D gene segments and possibly VH gene segments and a preponderance of productive rearrangements, primarily those expressing D gene segments in a preferred reading frame. The predominance of productively rearranged V genes with D regions translated in a preferred frame, is, at least in part, the consequence of selective clonal expansion encompassing at least five to six divisions subsequent to VH-D-JH rearrangement. Selection for clonal expansion appears to be dependent on recognition of the nascent H chain product of certain productively rearranged genes.
Cocaine potentiates HIV-1 replication in human peripheral blood mononuclear cell cocultures. Involvement of transforming growth factor-beta.
Authors: Peterson P K , Gekker G , Chao C C , Schut R , Molitor T W , Balfour H H 
Published: December 2022

Abstract
Cocaine use is an important high risk behavior in the AIDS epidemic. In this study, we tested the hypothesis that cocaine potentiates the replication of HIV-1 in human PBMC. A coculture system was used in which PBMC from healthy donors were incubated in the absence (control) or presence of cocaine before activation with PHA. Cocultures were then constituted with PBMC infected with a clinical isolate of HIV-1. HIV-1 replication, which was assessed by the measurement of HIV-1 p24 antigen levels in coculture supernatants, was significantly increased in a dose-dependent manner by cocaine with maximal stimulation at a concentration of 10(-9) M (965 +/- 196 vs 303 +/- 80 pg p24 Ag/ml in control cocultures). Antibodies to transforming growth factor-beta (TGF-beta) blocked cocaine-enhanced HIV-1 replication and purified TGF-beta stimulated viral replication in a manner similar to that observed with cocaine. Augmentation of HIV-1 replication by TGF-beta was maximal at a concentration of 0.01 ng/ml; however, viral proliferation appeared to be inhibited by concentrations of TGF-beta of 1 ng/ml or greater. Taken together, these results indicate that cocaine augments the replication of HIV-1 in PHA-activated PBMC via a mechanism that appears to involve TGF-beta.
Evidence for the targeting by 2-oxo-dehydrogenase enzymes in the T cell response of primary biliary cirrhosis.
Authors: Van de Water J , Ansari A A , Surh C D , Coppel R , Roche T , Bonkovsky H , Kaplan M , Gershwin M E 
Published: December 2022

Abstract
Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease that includes the presence of lymphoid infiltrates in portal tracts, high titer autoantibodies against pyruvate dehydrogenase-E2 (PDH-E2) and branched chain ketoacid dehydrogenase-E2 (BCKD-E2), and biliary tract destruction. The mechanism by which the autoimmune response is induced, the specificity of damage to the biliary epithelium, and the role of T cells in PBC are still unknown. To address these issues, we have taken advantage of a mouse mAb, coined C355.1, and studied its reactivity against a panel of liver tissue from normal subjects as well as a panel of liver specimens from patients with PBC, progressive sclerosing cholangitis, and chronic active hepatitis (CAH). C355.1, much like human autoantibodies to PDH-E2, reacts exclusively by immunoblotting with PDH-E2, binds to the inner lipoyl domain of the protein, and inhibits PDH-E2 activity in vitro. In addition, we have also attempted to develop cloned T cell lines that react with PDH-E2 and/or BCKD-E2 using liver biopsies from patients with PBC, compared with CAH. Although monoclonal C355.1 produced typical mitochondrial fluorescence on sections of normal liver, pancreas, lung, heart, thyroid, and kidney, it produced a distinct and intense reactivity when used to stain the bile ducts of patients with PBC. Nine of 13 PBC liver biopsies studied herein contained bile ducts on light microscopy, all of which reacted intensely at a 1:100 culture supernatant dilution of monoclonal C355.1. In contrast, although bile ducts of liver specimens from normals, CAH, and progressive sclerosing cholangitis also reacted with C355.1, such reactivity was exclusively mitochondrial and readily detectable only at a dilution of 1:2. More importantly, we generated CD4+, CD8-, alpha beta TCR+ cloned T cell lines from patients with PBC, but not from CAH, that produced IL-2 specifically in response to PDH-E2 or BCKD-E2.
In vivo administration of monoclonal antibodies to the CD3 T cell receptor complex induces cell death (apoptosis) in immature thymocytes.
Authors: Shi Y F , Bissonnette R P , Parfrey N , Szalay M , Kubo R T , Green D R 
Published: December 2022

Abstract
Some thymocytes, upon activation via the TCR complex in vitro, undergo apoptotic cell death. In this report, we examine the cell death induced in the thymus after administration of anti-CD3 or anti-TCR antibodies. We found that shortly after antibody injection, cortical thymocytes undergo apoptosis as characterized by morphologic changes and DNA fragmentation. Anti-CD3 administration led to depletion of nearly all CD4+CD8+ thymocytes, and approximately 50% of CD4+CD8- thymocytes. This depletion predominantly affected cells bearing low levels of CD3, although some depletion also occurred among cells expressing intermediate and high levels. Administration of an anti-TCR antibody also induced apoptosis, but affected significantly fewer thymocytes than anti-CD3. This effect was probably not due to different binding affinities for the two antibodies, because both antibodies show similar dose response effects in an in vitro model of activation-induced apoptosis. This work demonstrates that findings on activation-induced apoptosis in vitro can be extended to the in vivo situation, and further, that the activation of cortical thymocytes, in situ, results in apoptosis and removal of the activated cells. The possible relationships between this activation-induced cell death in immature thymocytes and the process of negative selection of autoreactive T cells is discussed.
IL-1 expression in human monocytes is transcriptionally and posttranscriptionally regulated by IL-4.
Authors: Donnelly R P , Fenton M J , Kaufman J D , Gerrard T L 
Published: December 2022

Abstract
The T cell-derived lymphokine, IL-4, inhibits production of IL-1 beta by normal human monocytes. To determine whether IL-4 suppresses IL-1 expression by a transcriptional and/or posttranscriptional mechanism, we evaluated the half-life of LPS-induced IL-1 beta message and transcriptional rate of the pro-IL-1 beta gene in human monocytes after treatment with IL-4. Although the initial steady-state IL-1 mRNA levels in control and IL-4-treated monocytes were comparable during the first 2 h after stimulation with LPS, IL-1 message levels subsequently decreased at a significantly greater rate in the IL-4-treated cells. Thus, IL-4 did not prevent the initial expression of IL-1 message, but did accelerate down-regulation of IL-1 mRNA in LPS-stimulated monocytes. The initial 2 to 3 h lag period may be necessary for production of a protein(s) that mediates this inhibitory effect because treatment with the protein synthesis inhibitor, cycloheximide, blocked the marked reduction of IL-1 message levels induced by IL-4. Nuclear run-on analyses demonstrated that IL-4 decreases IL-1 mRNA levels, in part, by repressing IL-1 gene transcription. Furthermore, mRNA half-life studies showed that IL-4 also significantly increases the rate of IL-1 message turnover in these cells. Together, these findings demonstrate that IL-4 inhibits IL-1 production in human monocytes by suppressing the formation of new IL-1 transcripts as well as by decreasing IL-1 message stability. In addition, the kinetics of inhibition and the fact that cycloheximide blocks this process suggest that IL-4 induces or enhances synthesis of a protein(s) that mediates these effects.
Inhibition of colony-stimulating factor-stimulated macrophage proliferation by tumor necrosis factor-alpha, IFN-gamma, and lipopolysaccharide is not due to a general loss of responsiveness to growth factor.
Authors: Vairo G , Argyriou S , Knight K R , Hamilton J A 
Published: December 2022

Abstract
The role of stimulatory factors, such as the CSF, in the regulation of hemopoiesis has been extensively documented. Less is known of the negative regulators of hemopoiesis. In this report, we show that the macrophage activating agents, TNF-alpha, IFN-gamma, and LPS, are all potent inhibitors of CSF-1-stimulated murine bone marrow-derived macrophage (BMM) DNA synthesis and increase in cell numbers. The inhibitory effects of TNF-alpha and IFN-gamma do not appear to be due to endotoxin contamination in the recombinant cytokine preparations. The inhibition of proliferation is reversible and is not due to a general loss of growth factor responsiveness, inasmuch as the three agents do not inhibit CSF-1-stimulated BMM survival, protein synthesis, or fluid phase pinocytosis. Because TNF-alpha and LPS are known to rapidly and potently down-modulate CSF-1 receptor levels in BMM, the results also suggest that low levels of receptor occupancy are sufficient for biological responses to CSF-1. The inhibitory effects of TNF-alpha, IFN-gamma, or LPS were also seen when granulocyte-macrophage-CSF or IL-3 was used to stimulate BMM DNA synthesis. The results suggest that TNF-alpha, IFN-gamma, and LPS appear to be inhibiting CSF-stimulated proliferation by acting at a post-receptor level, possibly by regulation of some critical event(s) in the mitogenic signaling pathway.