bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential inhibition of human neutrophil activation by cyclosporins A, D, and H. Cyclosporin H is a potent and effective inhibitor of formyl peptide-induced superoxide formation.
Authors: Wenzel-Seifert K , Grünbaum L , Seifert R 
Published: December 2022

Abstract
Cyclosporin (Cs)A but not CsH inhibits activation of human lymphocytes. We studied the effects of CsA, CsD, and CsH on human neutrophil activation induced by chemoattractants and by various substances that circumvent receptor stimulation. CsH inhibited superoxide (O2-) formation induced by the chemotactic peptide, FMLP (30 nM), with a half-maximal effect at 40 nM. O2- formation was abolished by CsH at 1 microM. CsH increased the concentration of FMLP causing half-maximal activation of O2- formation from 30 nM to 0.8 microM and substantially reduced the stimulatory effect of FMLP at supra-maximally effective concentrations. The inhibitory effect of CsH on O2- formation was evident immediately after addition to neutrophils. CsH also markedly inhibited the increase in cytosolic Ca2+ ([Ca2+]i), beta-glucuronidase, and lysozyme release and aggregation stimulated by FMLP. CsA and CsD were considerably less effective than CsH to inhibit FMLP-induced O2- formation. CsA and CsD were without effect on exocytosis, rises in [Ca2+]i, and aggregation induced by the chemotactic peptide. Cyclosporines inhibited FMLP-induced O2- formation in an additive manner, indicating that they acted through a mechanism they had in common. Cyclosporines only slightly inhibited O2- formation and lysozyme release induced by C5a. Aggregation and rises in [Ca2+]i stimulated by C5a were not affected by cyclosporines, and they did not inhibit O2- formation and exocytosis induced by platelet-activating factor and leukotriene B4. Cyclosporines partially inhibited O2- formations induced by NaF and gamma-hexachlorocyclohexane. CsA marginally inhibited PMA-induced O2- formation and lysozyme release. CsA, CsD, and CsH did not inhibit arachidonic acid-induced O2- formation and its potentiation by NaF or stable guanine nucleotides in a cell-free system from DMSO-differentiated HL-60 cells. CsH partially inhibited binding of FML [3H]P to formyl peptide receptors in membranes from DMSO- or dibutyryl cAMP-differentiated HL-60 cells. Our data show that: 1) cyclosporines differentially inhibit activation of human neutrophils; and 2) CsH is, indeed, not immunologically inactive but is a potent and effective inhibitor of FMLP-induced O2- formation. 3) CsH interferes with agonist binding to formyl peptide receptors and in addition, cyclosporines may also act at sites distal to chemoattractant receptors.
Human IgA1 blockade of IgG-initiated lysis of Neisseria meningitidis is a function of antigen-binding fragment binding to the polysaccharide capsule.
Authors: Jarvis G A , Griffiss J M 
Published: December 2022

Abstract
We have recently shown that human IgA1 can initiate lysis of group C Neisseria meningitidis via the classical C pathway when bound to specific outer membrane proteins, but that IgA1 can also function as a blocking antibody when bound to the polysaccharide capsule of meningococci. In this report, we further characterized IgA1 blockade by examining the effect of IgA1 on IgG-initiated immune lysis of group C meningococci. We purified IgG and monomeric IgA1 from either convalescent group C meningococcal case sera or tetravalent (A, C, Y, W135) polysaccharide vaccinate sera. In the absence of IgA1, IgG initiated complete lysis (greater than 99%) of strains 118V (C:P3,4:L2,4) 126E (C:P3:L1,8), and 35E (C:P5:L2). Addition of IgA1 to the bactericidal reaction mixture completely blocked the lytic function of IgG. Removal of the Fc portion of IgA1 with either pepsin or IgA1 protease did not affect blockade. Both the F(ab')2 and Fab derivatives of IgA1 blocked lysis quantitatively as well as intact IgA1. The Fc fragment produced by IgA1 protease cleavage neither increased nor decreased Fab-mediated blockade. IgA1 and its Fab and F(ab')2 fragments blocked IgG-initiated lysis via either the classical pathway in factor B-depleted and in properdin-deficient serum, the alternative pathway in MgEGTA-chelated serum, or both pathways combined. Absorption of the IgA1 and IgG with alum-bound group C polysaccharide completely removed blocking and lytic activity, respectively, indicating that both the blocking IgA1 and the lytic IgG were specific for the group C capsule. Blocking by IgA1 was a linear function of the polysaccharide Ag-binding capacity (ABC) ratio of blocking IgA1 to lytic IgG. Complete blockade was observed at an ABC ratio of 5.5. At ABC ratios of 3.3 and 4.4, IgA1 affected significant blockade whether added previous to, concurrent with, or subsequent to sensitization of the organisms with IgG. With the use of a C polysaccharide ELISA, we found that the binding of IgA1 to the group C capsule in the presence of IgG exhibited positive cooperativity and therefore that blockade was independent of the ability of IgA1 to directly compete with IgG for binding to epitopes within the group C capsule. We conclude that IgA1, when bound to the group C polysaccharide capsule, can block IgG-initiated lysis of group C meningococci through either the classical or the alternative pathway before or after the organism is exposed to IgG, and that blockade is an Fc-independent event.
Recognition of chromosome 6-associated target structures by human lymphokine-activated killer cells.
Authors: Helander T , Timonen T , Kalliomäki P , Schröder J 
Published: December 2022

Abstract
Different populations of unstimulated and IL-2-activated PBL were used in binding and killing assays against somatic mouse/human lymphocyte cell hybrids containing different human chromosomes. Unstimulated PBL effector cells showed low binding and killing activity to both cell hybrids and mouse parental cell lines. However, IL-2-activated killer (LAK) cells bound strongly to, and effectively killed, cell hybrids carrying human chromosome 6, but were inefficient in both assays to mouse parental cells and to cell hybrids not carrying human chromosome 6. These results show that human LAK cells but not endogenous NK cells bind and kill mouse/human lymphocyte hybrids containing human chromosome 6. We thus suggest that LAK cells recognize ligands encoded by genes on chromosome 6.
T cell receptor gene segment utilization by HLA-DR1-alloreactive T cell clones.
Authors: Geiger M J , Gorski J , Eckels D D 
Published: December 2022

Abstract
Transplantation of histoincompatible tissues leads to allograft rejection, which involves recognition of allogeneic MHC molecules by Ag-specific receptors expressed on T cells. The interaction of these molecules is highly specific yet poorly understood. We have investigated the relationship between TCR gene utilization and allo-MHC restriction patterns by using a one-way polymerase chain reaction to amplify the alpha- and beta-chain mRNA from a panel of 10 HLA-DR1-alloreactive T lymphocyte clones. Two previously unreported V alpha and five J alpha gene sequences were obtained. Although a few V alpha, V beta, and J alpha genes were utilized more than once, no correlation between TCR gene usage and DR1 alloreactivity was identified. At the sequence level, the presumed TCR alpha- and beta-chain CDR1 and CDR2 regions displayed limited diversity, whereas the CDR3 or junctional sequences were highly variable. Although most TCR probably interact with subtly different surface features of the DR1 alloantigen, we predict that TCR with similar CDR1 and CDR2 sequences would contact essentially identical regions of the DR1 molecule. The lack of sequence conservation in the junctional regions suggests that different endogenous peptides also may be recognized. Thus, alloreactive T cells may recognize not only allogeneic MHC molecules but perhaps also bound endogenous peptides.
Myosin-induced acute myocarditis is a T cell-mediated disease.
Authors: Smith S C , Allen P M 
Published: December 2022

Abstract
The heart is a target organ in several autoimmune diseases, and therefore it is important to understand more about the effector cells involved in immune-mediated mechanisms of myocardial cell death. Because immune T lymphocytes are central to many immune responses, we wanted to study the role of T cells in causing cardiac specific inflammation. We used purified mouse cardiac myosin to cause acute myocarditis in mice. The adoptive transfer of purified T cells from C.B-17 mice with active myocarditis to SCID recipients successfully transferred the disease into SCID hosts. In contrast, transfer of serum with high-titer antimyosin antibodies to SCID hosts did not cause myocarditis. Using mAb to deplete A/J mice of CD4+ T cells, we showed that these mice were protected against the induction of myocarditis. Depletion of CD8+ T cells reduced the severity of inflammation but did not prevent induction of myocarditis. We were also able to prevent the induction of myocarditis using major histocompatibility class II protein-binding, nonimmunogenic, competitor peptides. These blocking studies also indicated that in H-2k mice, myocarditis is an I-Ak-restricted disease, and provided further evidence that CD4+ T cells are critical to the induction of disease. Together, these studies provide direct evidence that myosin-induced myocarditis is a T cell-mediated disease.
Effects of IL-7 and IL-2 on highly enriched CD56+ natural killer cells. A comparative study.
Authors: Naume B , Espevik T 
Published: December 2022

Abstract
IL-7 has been shown to induce low levels of lymphokine-activated killer cell (LAK) activity in bulk PBMC populations. We report here that immunomagnetically purified CD56+ cells from peripheral blood generated high LAK activity in response to IL-7. The LAK activity induced by IL-7 was comparable to, or slightly lower than, the LAK activity induced by IL-2. When analyzing cells from the same donor, no detectable LAK-generating effect of IL-7 was registered in the PBMC population, in contrast to a substantial effect in the CD56+ population. IL-2 induced 8- to 15-fold higher proliferative activity in CD56+ cells, relative to IL-7. At suboptimal concentrations of IL-2, IL-7 had a synergistic effect on the proliferation. IL-2-neutralizing antibodies did not abrogate the IL-7-induced proliferation or LAK generation. Both IL-7 and IL-2 induced comparable levels of 75-kDa TNFR expression, whereas IL-2R alpha expression was higher in IL-7-stimulated CD56+ cells. Low levels of TNF were produced in response to IL-7 at day 5, as opposed to a 50-fold higher TNF production in response to IL-2. No IL-2 or IL-6 production was detected. Our data indicate that IL-7 has profound and direct effects on CD56+ cells.
The signal transduction pathway involved in the migration induced by a monocyte chemotactic cytokine.
Authors: Sozzani S , Luini W , Molino M , Jílek P , Bottazzi B , Cerletti C , Matsushima K , Mantovani A 
Published: December 2022

Abstract
Recombinant monocyte-chemotactic and activating factor (rMCAF; alternative acronyms MCP-1, TDCF, human JE) induced migration of human monocytes across polycarbonate or nitrocellulose filters. Maximal induction of migration was observed at a concentration of 10 ng/ml (10(-9) M). Checkerboard analysis revealed that rMCAF elicited true gradient-dependent chemotactic migration, although a gradient independent chemokinetic effect was observed at low concentrations (1-5 ng/ml). rMCAF caused a rapid (less than 5 s) and transient (approximately 1.5 min) increase of free cytosolic Ca2+ ions, as assessed by the fura-2 probe. No Ca2+ increase was detected in neutrophils or lymphocytes stimulated by rMCAF. Studies conducted in the absence of extracellular Ca2+ or in the presence of Ni2+ (an inhibitor of Ca2+ influx) suggested that the increase of intracellular Ca2+ induced by rMCAF is dependent on the influx of extracellular Ca2+ through plasma membrane channels. Bordetella pertussis toxin inhibited the intracellular Ca2+ elevation and chemotaxis caused by rMCAF. The possible involvement of Ca(2+)-dependent protein kinases in rMCAF signaling pathway(s) was explored using inhibitors. Inhibitors of GMP-dependent kinase and myosin L chain kinase had no effect on rMCAF-induced monocyte migration. In contrast, protein kinase C/cAMP-dependent kinase inhibitors (such as, C-I, H-7, HA-1004, KT5720, and Staurosporine) markedly decreased rMCAF induced chemotaxis suggesting the involvement of a serine/threonine protein kinase, possibly protein kinase C, in rMCAF signaling pathway.
Human immune response in Plasmodium falciparum malaria. Synthetic peptides corresponding to known epitopes of the Pf155/RESA antigen induce production of parasite-specific antibodies in vitro.
Authors: Chougnet C , Troye-Blomberg M , Deloron P , Kabilan L , Lepers J P , Savel J , Perlmann P 
Published: December 2022

Abstract
Autologous cell mixtures containing T cells, B cells, and adherent accessory cells from individuals primed to the malaria parasite Plasmodium falciparum by repeated natural infections were investigated for induction of Ig and antibody secretion in vitro. In vitro activation of cell cultures with two synthetic peptides corresponding to immunodominant T cell epitopes of the merozoite Ag ring-infected erythrocyte surface Ag (Mr 155,000) (Pf155/RESA), one from its carboxyl-terminal repeat and one from its nonrepeated amino-terminal region, gave rise to significant IgG secretion. Supernatants from lymphocyte cultures activated with either one of these peptides contained antibodies reacting with P. falciparum Ag in immunofluorescence assays and with Pf155/RESA peptides in a slot blot assay. No anti-P. falciparum antibodies were induced in the medium controls by lymphocyte stimulation with either tetanus toxoid or PWM. Induction in vitro of anti-Pf155/RESA antibodies was correlated with the presence of such antibodies in the sera of the lymphocyte donors, suggesting that the induction of antibody secretion reflected a secondary response in vitro of in vivo primed cells. Inspection of antibody profiles in individual donors revealed that the peptide corresponding to a sequence in the 3' repeat region induced anti-Pf155/RESA peptide antibodies reacting with identical or related and cross-reacting sequences in the 3' or 5' repeat region of the molecule. In contrast, the peptide corresponding to a nonrepeated T cell epitope in the amino terminus of the molecule only induced antibodies to an immunodominant amino-terminal B cell epitope partly overlapping with the T cell reactive sequence. Similar findings were made in the lymphocyte donors' plasma, frequently displaying significant correlations between antibody reactivities to the repeat peptides but not between these reactivities and those to the amino-terminal peptide. The marked specificity of this antibody formation in vitro suggests an underlying process of cognate recognition involving Ag-specific T and B cells reacting with different segments of the inducer peptide. The present experimental system should be well suited for identification of Th epitopes capable of inducing the production of antibodies of defined specificity in the human system.
Epitope recognition of conserved HIV envelope sequences by human cytotoxic T lymphocytes.
Authors: Dadaglio G , Leroux A , Langlade-Demoyen P , Bahraoui E M , Traincard F , Fisher R , Plata F 
Published: December 2022

Abstract
CTL constitute an essential part of the immune response against the HIV. CTL recognize peptides derived from viral proteins together with the MHC class I molecules on the surface of infected cells. The CTL response could be important in prevention or control of infection with HIV by destroying virus-producing cells. In this study we have attempted to identify peptide epitopes recognized by HIV-specific CTL. Using synthetic peptides, we have identified six conserved peptidic epitopes on the gp120 envelope glycoprotein recognized by polyclonal human CTL in association with HLA-A2 class I transplantation Ag. These results were confirmed by two approaches: i) blocking of CTL activities with antibodies specific for three of these conserved peptides; and ii) construction of doubly transfected P815-A2 target cells, using deletions of the HIV env gene. Vaccination or immunotherapy in HLA-A2 individuals can thus be considered using highly conserved HIV env peptidic sequences.
CD8+ T cells from mice vaccinated against Toxoplasma gondii are cytotoxic for parasite-infected or antigen-pulsed host cells.
Authors: Hakim F T , Gazzinelli R T , Denkers E , Hieny S , Shearer G M , Sher A 
Published: December 2022

Abstract
Mice vaccinated with a live temperature sensitive mutant (TS-4) of Toxoplasma gondii develop complete resistance to subsequent challenge with a highly virulent Toxoplasma strain (RH). Because CD8+ T cells have been demonstrated to be critical to this protective immunity in vivo, the involvement of cytotoxic T lymphocytes in the killing of infected cells in vaccinated mice was investigated. After restimulation in vitro, splenic T cells from vaccinated mice of either the BALB/c or C57BL/6 strains were found to kill syngeneic bone marrow-derived macrophages infected with TS-4 tachyzoites or preincubated with soluble T. gondii Ag. Unimmunized control mice or mice vaccinated with heat-killed TS-4 tachyzoites failed to generate significant CTL activity in vitro. Moreover, the observed lytic reaction was found to be target specific, not killing uninfected or unpulsed macrophages even when included as bystanders in the assay. Target lysis did not depend on the production by the effector cells of either a cytotoxic supernatant factor or IFN-gamma. Depletion of CD8+ cells from the splenic effector cell population, however, abrogated the cytotoxic activity, whereas depletion of CD4+ cells had little effect. The MHC restriction of the Toxoplasma-specific cytolytic reaction was confirmed in studies using effector cells from BALB/c mice and targets from congenic or mutant haplotype strains. These experiments indicated that target killing is primarily restricted by genes mapping within the H-2D/Ld loci. Together, these results establish MHC-restricted cytolysis as a major parameter of CD8+ effector function against T. gondii and indicate that, in the case of this protozoan, Ag presentation to CD8+ lymphocytes can occur as a result of either processing within infected cells or exogenous uptake of parasite Ag.
Tumor necrosis factor-alpha triggers antitoxoplasmal activity of IFN-gamma primed macrophages.
Authors: Sibley L D , Adams L B , Fukutomi Y , Krahenbuhl J L 
Published: December 2022

Abstract
IFN-gamma is an important mediator of cellular resistance against microbial pathogens and tumor cells due in part to its potent capacity to activate macrophages for enhanced cytotoxicity. The present study demonstrates that TNF-alpha regulates the expression of enhanced antimicrobial activity by triggering IFN-gamma primed macrophages to kill or inhibit intracellular Toxoplasma gondii. Resident mouse macrophages stimulated with rIFN-gamma at levels up to 2500 U/ml failed to display enhanced antitoxoplasmal activity when cultured in vitro under low endotoxin conditions (less than 10 pg/ml), but were triggered by addition of small amounts of LPS (0.1 ng/ml). A similar requirement for LPS as a second signal necessary to trigger antitoxoplasmal activity was observed when IFN-gamma was administered to mice in vivo. The essential nature of this triggering step allowed us to explore the role of cytokines that act as endogenous regulators of macrophage activation. rTNF-alpha, although unable to confer antitoxoplasmal activity when used alone to treat macrophages, was capable of triggering IFN-gamma-primed macrophages cultured under low endotoxin conditions. The ability of TNF-alpha to trigger IFN-gamma-primed macrophages was blocked by rabbit anti-TNF-alpha polyclonal antisera but was not affected by polymyxin B indicating that TNF-alpha triggering was not due to contamination with LPS. Collectively, these findings demonstrate that TNF-alpha performs an important regulatory role in the expression of enhanced anti-microbial activity by IFN-gamma-primed macrophages.
Interactions between the amino-terminal domains of MHC class II molecules have a profound effect on serologic and T cell recognition: an analysis using recombinant HLA-DR/H-2E molecules.
Authors: Barber L D , Lechler R I 
Published: December 2022

Abstract
A series of transfected L cell lines were generated expressing the products of wild-type or recombinant HLA-DR1/H-2Ek beta-chain-encoding genes paired to DR alpha or E alpha. The recombinant genes were created by reciprocal exchange of the gene segments encoding the amino (NH2)-terminal and carboxy (COOH)-terminal halves of the beta 1 domain and the beta 2 domain. The majority of the serologic determinants, predicted from the genetic composition of the class II dimers, were expressed indicating that no gross conformational changes were induced by the creation of the interspecies recombinant molecules. Subtle conformational variation was detected by the anti-H-2Eb,k,s mAb Y17. Epitope expression was dependent on the presence of the E alpha-chain and NH2-terminal sequence from the beta 1 domain of H-2Ek. Substitution of DR1 sequence in either region led to loss of recognition by Y17. This pattern of reactivity maps the Y17 epitope either to the E alpha-chain or to an exposed sequence on the fourth strand of the beta sheet of the beta 1 domain. If the Y17 epitope is located on the E alpha-chain this raises the interesting possibility that the conformation of this chain, which is invariant by sequence, may vary according to the beta-chain with which it is coexpressed. The ability of the recombinant class II dimers to present Ag to the pigeon cytochrome c-specific, H-2Ek-restricted T cell hybridoma 2B4 was assessed. Transfected L cells expressing E beta k paired to E alpha or DR alpha presented Ag with equal efficiency, and the beta 2 domain of H-2Ek could be substituted with the equivalent region from DR1 without any loss of response. Wild-type DR1 failed to function as a restriction element, however, substitution of the COOH-terminal portion of the beta 1 domain with the equivalent sequence from H-2Ek was sufficient to produce a partial recovery of Ag recognition. Cells expressing a recombinant beta 1 domain comprising the COOH-terminal sequence from H-2Ek and the NH2-terminal sequence from DR1 presented Ag when paired to DR alpha but failed to do so when paired to E alpha. This indicates that a subtle conformational disturbance caused by mismatching of the NH2-terminal region of the beta-chain and the alpha-chain can have pronounced effects on T cell recognition.(ABSTRACT TRUNCATED AT 400 WORDS)