bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific V beta T cell subsets mediate the immediate hypersensitivity response to ragweed allergen.
Authors: Renz H , Saloga J , Bradley K L , Loader J E , Greenstein J L , Larsen G , Gelfand E W 
Published: December 2022

Abstract
T and B cell responses after sensitization to ragweed (RW) were examined in a mouse model in which BALB/c mice were exposed to the allergen by ultrasonic nebulization. Sensitization resulted in the stimulation of an IgE anti-RW response and was paralleled by a rise in IgG1 anti-RW titers. Skin testing for immediate cutaneous hypersensitivity revealed the presence of allergic type I reactions to RW. Sensitization to RW in this way was also associated with the development of increased airways responsiveness as determined by electrical field stimulation of preparations of tracheal smooth muscle. Histologic examination of the airways and the lung indicated the presence of a mononuclear cell infiltrate in the mucosa and submucosa of the airways that was accompanied by an enlargement of local draining lymph nodes of the airways and the lung. T cell populations were analyzed for the frequency of V beta-expressing T cells. Such analysis indicated that RW sensitization stimulated the expression of V beta 8.1+, V beta 8.2+, and V beta 13+ T cells in the local lymphoid tissue and of V beta 8.1+, V beta 8.2+, V beta 8.3+, V beta 9+ and V beta 14+ T cells in the spleen. Co-culture of these T cell populations with RW-primed B cells indicated that in the presence of RW, V beta 8.2 T cells stimulated IgE and IgG1 production, whereas the other T cell populations showed a different stimulation profile for Ig isotypes and IgG subclasses. The transfer of V beta 8.2 T cells from sensitized but not from nonsensitized control mice stimulated an allergen-specific IgE and IgG1 response and increased airways responsiveness in naive recipients. These data provide additional support for the pivotal role of specific V beta-expressing T cell subpopulations in the stimulation of IgE/IgG1 production and increased airways responsiveness.
Anti-TAPA-1 antibodies induce protein tyrosine phosphorylation that is prevented by increasing intracellular thiol levels.
Authors: Schick M R , Nguyen V Q , Levy S 
Published: December 2022

Abstract
We studied the signal induced by the anti-TAPA-1 antibody and compared it to the signal induced by anti-IgM antibodies in a human B cell line, OCl-LY8. We found that exposure of these cells to either antibody resulted in a rapid increase in protein tyrosine phosphorylation which was prevented by inhibitors of tyrosine kinases. Tyrosine phosphorylation was an early event in the cascase leading to the antiproliferative effect of the anti-TAPA-1 antibody. However, 2-ME, a reducing agent that is not an inhibitor of tyrosine kinases, prevented both tyrosine phosphorylation and the antiproliferative effect of the antibody. Cells grown in low concentrations of 2-ME did not exhibit an increase in tyrosine phosphorylation in response to the anti-TAPA-1 antibody and were insensitive to the antiproliferative effect of the antibody. In contrast, the same cells maintained in 2-ME were able to induce tyrosine phosphorylation in response to anti-IgM. The use of 2-ME resulted in an increase in intracellular thiols, mostly glutathione. Moreover, compounds that block glutathione synthesis rendered cells susceptible to the antibody, even in the presence of 2-ME. These experiments demonstrate that tyrosine kinases are involved in propagating the antiproliferative signal initiated by the anti-TAPA-1 antibody and suggest that this signal is dependent upon the level of intracellular thiols.
Antigen presentation capacity of murine macrophages infected with Leishmania amazonensis amastigotes.
Authors: Prina E , Jouanne C , de Souza Lão S , Szabo A , Guillet J G , Antoine J C 
Published: December 2022

Abstract
Leishmania-infected M phi are potential candidates for the presentation of parasite Ag to Leishmania-specific CD4+ T lymphocytes. To assess whether infected cells could function as APC, we examined the ability of bone marrow-derived M phi infected with Leishmania amazonensis amastigotes to stimulate various CD4+, l-Ad- or l-Ed-restricted T-cell hybridomas specific for the bacteriophage lambda repressor cl protein, the human chorionic gonadotropin or OVA. A reduced capacity of infected M phi to present native Ag to most T-cell hybridomas tested was noted that was probably a result of a lower expression on their plasma membrane of stimulatory [la-peptide] complexes. Neither a reduced Ag uptake nor an altered Ag processing appeared to be at the origin of the partial inability of infected M phi to present Ag. As regards the level of plasma membrane la expression, no quantitative difference could be detected between uninfected and infected M phi. Moreover, after fixation with paraformaldehyde, the ability of plasma membrane la molecules to bind immunogenic peptides was apparently not reduced in infected M phi. So, these cells most likely expressed functional la molecules on their cell surface. Interestingly, infected M phi and M phi infected then cured by a treatment with a leishmanicidal compound were similarly impaired in their capacity to present native Ag or peptides to the hybridomas, and no recovery was noted even 24 h after the leishmanicidal treatment. Furthermore, infected M phi and M phi incubated with heat-killed amastigotes or with an amastigote homogenate exhibited similar inhibitions of Ag presentation. Taken together, these results suggest that the functional failure of infected M phi to present exogenous Ag could be because either of interferences with the events leading to the meeting of la molecules with peptides derived from these exogenous Ag or to a competition for binding to la molecules between these peptides and parasite molecules.
Targeted activation of CD8 cells and infection of beta 2-microglobulin-deficient mice fail to confirm a primary protective role for CD8 cells in experimental leishmaniasis.
Authors: Wang Z E , Reiner S L , Hatam F , Heinzel F P , Bouvier J , Turck C W , Locksley R M 
Published: December 2022

Abstract
CD8+ T cells play an important role in the immunologic control of intracellular pathogens, particularly viruses. Leishmania are obligate intracellular parasites of macrophages in the mammalian host, and previous studies using deletion of CD8+ cells by administration of mAb to infected animals have suggested a protective role for these cells. Two complementary approaches were used to define more carefully the role of CD8+ cells in leishmaniasis. In BALB/c mice susceptible to Leishmania major (L. major) infection, targeted activation of CD8+ T cells was attempted by immunization with nonapeptides derived from the conserved major outer surface protein of the organism, gp63, that contained the consensus binding motif for MHC class I H-2Kd molecules. Two of the nonapeptides induced CTL activity in subsequently infected BALB/c mice that could be elicited against P815 cells pulsed either with peptide or lysates of L. major. Purified CD8+ T cells from immunized mice had elevated levels of IFN-gamma mRNA transcripts as compared to unimmunized mice. Despite evidence for activation of CD8+ cells, none of the mice immunized with nine different peptides alone or in combination were protected from progressive disease. In a second series of experiments, beta 2-microglobulin deficient mice that lack CD8+ cells were infected with L. major and the course of infection monitored. These mice cured disease as rapidly as beta 2-m +/- and +/+ littermates, and cure was associated with comparable levels of IFN-gamma mRNA in the draining lymph node population. Neither of these approaches was able to confirm a substantive role for CD8+ T cells in the primary protective response to L. major.
Receptor-ligand interactions between serum amyloid P component and model soluble immune complexes.
Authors: Brown M R , Anderson B E 
Published: December 2022

Abstract
We report here that isolated human serum amyloid P (SAP) binds aggregates of human IgG (AAg), which are model soluble immune complexes. The binding interaction was specific with regard to AAg compared to monomeric IgG, saturable, of high affinity, and reversible. With SAP adsorbed to microtiter plate wells, protein binding assays of AAg preparations with m.w. values of 1.05 to 2.25 x 10(6) were performed. The assay results yielded binding isotherms and estimates of the dissociation constant values of SAP:AAg binding ranging between 0.60 and 1.9 nM. Using the same method, the dissociation constant of SAP binding of biotinylated AAg was estimated to be approximately 3.0 nM. Competitive protein binding assays using biotinylated AAg and unlabeled AAg or monomeric IgG were performed to determine the relative affinity (IC50) of SAP binding. The IC50 values ranged from 22 to 51 nM for different sizes of AAg. The IC50 determined for monomeric IgG was 10 microM, demonstrating a relative specificity of SAP binding for AAg. The binding interaction was reversible, the SAP:AAg complexes dissociating with a t1/2 of 125 min. AAg binding to solid phase-adsorbed SAP was not dependent upon the presence of several cations, including calcium, but was not supported by cuprous ion. The differential binding of AAg vs monomeric IgG reported here for SAP is similar to the other human immune complex binding proteins C1q, rheumatoid factor, and cellular Ig C-region receptors. These results indicate that SAP:AAg binding has the hallmarks of a receptor:ligand interaction and may have implications for the disposal of immune complexes in vivo.
Quantitation and kinetics of blood monocyte migration to acute inflammatory reactions, and IL-1 alpha, tumor necrosis factor-alpha, and IFN-gamma.
Authors: Issekutz A C , Issekutz T B 
Published: December 2022

Abstract
Monocytes migrate from the blood into acute inflammatory reactions, where they differentiate into macrophages, and after 12 to 24 h become the predominant histologic feature of the inflammatory infiltrate. The quantitation of monocyte migration into these reactions has been difficult. This report employs a novel combination of techniques to isolate highly purified monocytes from the blood of rats, and shows that these cells have a normal t1/2 of 26 h and migrate efficiently after i.v. injection into cutaneous acute inflammatory sites. Monocytes labeled with 51Cr accumulated in delayed-type hypersensitivity reactions, and sites injected with killed Escherichia coli, LPS, poly-inosine: cytosine, zymosan-activated serum (ZAS), a source of C5adesArg, and the cytokines IL-1 alpha, TNF-alpha, and IFN-gamma. Both radiolabeled monocytes and neutrophils migrated rapidly to E. coli, LPS, ZAS, IL-1 alpha, and TNF-alpha with a large increase in cell accumulation by 2 h. Neutrophil migration declined rapidly to undetectable levels by 3 to 4 h to all five stimuli, and monocyte migration to ZAS and IL-1 alpha also declined by this time. In contrast, E. coli, LPS, and TNF-alpha caused a sustained migration of monocytes for 5 to 6 h, long after neutrophils had stopped accumulating. Intradermal IFN-gamma did not recruit neutrophils but stimulated a prolonged monocyte migration from 1 to 6 h. Combinations of LPS, TNF-alpha, and IFN-gamma synergistically enhanced the late (&gt; 5 h) but not the early phase of monocyte recruitment. In conclusion, purified monocytes isolated from rat blood can be used to quantify monocyte migration in vivo, and these cells migrate rapidly to cutaneous inflammation and in response to chemotactic factors, IL-1 alpha, TNF-alpha, and IFN-gamma, with initial kinetics similar to those of neutrophils. However, monocyte-selective mechanisms are induced by IFN-gamma and also appear to be involved in prolonged monocyte migration to TNF-alpha, LPS, and E. coli.
Microglial cell cytotoxicity of oligodendrocytes is mediated through nitric oxide.
Authors: Merrill J E , Ignarro L J , Sherman M P , Melinek J , Lane T E 
Published: December 2022

Abstract
Rat ameboid microglia are able to lyse rat oligodendrocytes in vitro. The lysis is inhibited by transforming growth factor-beta, antagonists of nitric oxide (NO) production, as well as antibodies to TNF-alpha, intercellular adhesion molecule-1 (ICAM-1), and leukocyte functional Ag-1. Ameboid microglial cells spontaneously produce detectable levels of the NO metabolite nitrite (NO2-). Stimuli such as PMA, LPS, and/or IFN-gamma induce micromolar concentrations of NO2- within 24 h. TNF-alpha increases IFN gamma but not LPS-induced NO2- production. Incubation with target oligodendrocytes also increases NO2- production in a contact-dependent manner. NO2- production is inhibited by NO synthase antagonists, transforming growth factor-beta, and anti TNF-alpha. Neither antileukocyte functional Ag-1 nor anti-ICAM-1 inhibit NO2- production by microglia in the presence or absence of oligodendrocytes. Indeed, anti-ICAM-1 treatment increases NO2- production. There is a correlation between ameboid microglial cell killing of oligodendrocytes and NO2- production suggesting NO may be a mechanism of death of the oligodendrocyte and possibly play a role in lesion formation in multiple sclerosis.
Mechanism of increased tumor necrosis factor production after thermal injury. Altered sensitivity to PGE2 and immunomodulation with indomethacin.
Authors: Molloy R G , O'Riordain M , Holzheimer R , Nestor M , Collins K , Mannick J A , Rodrick M L 
Published: December 2022

Abstract
Altered macrophage function after thermal injury is associated with increased production of PGE2 and TNF. However, it is not clear why synthesis of both cellular products remains elevated, as PGE2 is a potent inhibitor of TNF secretion. We studied the relationship between PGE2 and TNF synthesis in a murine model of thermal injury, and examined the effect of prostaglandin blockade on splenic macrophage secretion of these mediators of inflammation. LPS-stimulated production of PGE2 was significantly elevated in burn groups compared with sham-burned controls (pg/ml mean(SEM); sham 151(32): burn 597(147), p &lt; 0.01). TNF production was similarly increased after thermal injury (pg/ml mean(SEM); sham 62(20): burn 928(316), p &lt; 0.01). In vitro culture of macrophages with indomethacin augmented LPS stimulated TNF production in sham-burned controls but did not affect synthesis in burn groups, suggesting a loss of PGE2-dependent regulation of TNF synthesis after thermal injury. Direct measurement of TNF secretion as a function of exogenous PGE2 confirmed this dissociation between PGE2 and TNF synthesis, as burned animals displayed a 5-fold reduction in sensitivity to PGE2-induced inhibition of TNF, when compared with sham-burned controls (ID50 PGE2 molar; sham 1.26 x 10(-8): burn 6.43 x 10(-8), p &lt; 0.05). In vivo pretreatment of burn groups with indomethacin for 5 days before assay partially restored sensitivity to the prostaglandin, and significantly down-regulated synthesis of both TNF and PGE2. These data show that thermal injury is associated with a loss of PGE2-dependent down-regulation of TNF synthesis, which accounts at least in part for increased TNF in these animals. In vivo cyclooxygenase blockade partially restored sensitivity to the prostaglandin and consequently down-regulated synthesis of TNF. These data further support existing evidence that suggests a potential therapeutic role for cyclooxygenase blockade after major thermal injury and trauma.
Cord blood contains high numbers of autoimmune T cells recognizing multiple myelin proteins and acetylcholine receptor.
Authors: Fredrikson S , Sun J B , Huang W X , Li B L , Olsson T , Link H 
Published: December 2022

Abstract
To analyze Ag-specific T cell autoimmunity in the newborn, umbilical cord blood cells of newborns were investigated by an immunospot assay for occurrence and numbers of cells secreting IFN-gamma after short-term culture in presence of myelin basic protein (MBP), proteolipid protein, myelin associated glycoprotein, nicotinic acetylcholine receptor and the synthetic MBP amino acid sequences 1-20, 63-88, and 110-128. These Ag were chosen because they represent putative targets for autoimmune attack in multiple sclerosis and myasthenia gravis. Surprisingly, numbers of T cells recognizing MBP, proteolipid protein, MBP peptides, and acetylcholine receptor were high in cord blood of newborns compared to peripheral blood of patients with neurologic diseases. No immunodominant T cell epitope could be discerned among the Ag included. The responses to purified protein derivate and PHA were lower among cord blood cells than peripheral blood cells of adults. Parallel enumeration of autoimmune T cells in cord blood and peripheral blood obtained from corresponding mothers at delivery, revealed that the high cell numbers in newborns were not a result of contamination from the mothers blood. The high numbers of T cells recognizing nervous system myelin proteins and acetylcholine receptor in cord blood could have importance for the mechanism and timing of tolerance induction, and also reflect excessive myelination and receptor maturation at birth.
In vivo antigen presentation by both brain parenchymal cells and hematopoietically derived cells during the induction of experimental autoimmune encephalomyelitis.
Authors: Myers K J , Dougherty J P , Ron Y 
Published: December 2022

Abstract
A fundamental issue in the etiology of autoimmune diseases of the central nervous system such as multiple sclerosis and its animal counterpart experimental autoimmune encephalomyelitis (EAE) concerns the identity of cells capable of presenting autoantigen to the T cells that mediate these diseases. The prevailing dogma is that only bone marrow-derived cells function as APC during EAE induction. We have addressed this issue by studying EAE induction in mouse bone marrow chimeras, and have found that although bone marrow-derived APC such as macrophages and brain microglial cells are more efficient at presenting autoantigen, brain parenchymal cells such as astrocytes and endothelial cells are also capable of inducing disease. EAE was induced in these chimeras by the adoptive transfer of encephalitogenic T cell lines designed to be MHC-histocompatible with APC contained either within the hematopoietic system of the chimera or with APC resident to the brain of the chimera. The subsequent development of EAE in these chimeras then indicated which population of cells served as in vivo APC during EAE pathogenesis. Possible effects of alloreactivity between the host chimera and the adoptively transferred T cells were eliminated by using encephalitogenic T cell lines made tolerant to the haplotype(s) of the recipient chimera.
A humanized CD18 antibody can block function without cell destruction.
Authors: Sims M J , Hassal D G , Brett S , Rowan W , Lockyer M J , Angel A , Lewis A P , Hale G , Waldmann H , Crowe J S 
Published: December 2022

Abstract
Leukocyte integrins are intimately involved in transient adherence of leukocytes to endothelium and to each other in the processes of extravasation and cell activation. In this study, seven mAb directed against human CD11a and two mAb directed against human CD18, the alpha- and beta-chains of the leukocyte functional Ag-1 molecule, respectively, were analyzed for their ability to inhibit several leukocyte functional Ag-1-mediated interactions. The best blocking mAb in these studies, a rat anti-human CD18, YFC51.1, was subsequently humanized by complementarily-determining region grafting, associated with human C regions and expressed. The humanized mAb was shown to maintain binding for human CD18. Even though the humanized mAb was an IgG1 isotype it still retained the functional blocking characteristics of the rat mAb while failing to mediate cell killing. The IgG1 mAb was unable to bind human Clq and could block but did not mediate antibody-dependent cellular cytotoxicity.
Modulation of perforin and granzyme messenger RNA expression in human natural killer cells.
Authors: Salcedo T W , Azzoni L , Wolf S F , Perussia B 
Published: December 2022

Abstract
Perforin and granzymes are proteins thought to play a relevant role in cell-mediated cytotoxicity. These molecules are constitutively expressed in NK cells and their level of expression in cytotoxic T lymphocytes is regulated by several cytokines. We analyzed the mechanisms by which cytokines and cellular ligands known to modulate NK cell-mediated cytotoxicity affect the expression of the mRNA encoding granzyme A and B and perforin in NK cells. Our data indicate that IL-2 and IL-12 induce increased accumulation of both perforin and, to a higher degree, granzyme B mRNA. In contrast, binding of target cells or immune complexes up-regulates expression of granzyme B mRNA without altering that of perforin. Results of in situ hybridization experiments confirm that mRNA for both molecules are expressed at low levels in most NK cells, and that both are induced to accumulate by the two cytokines in the majority of the cells. The mechanisms by which IL-2 and IL-12 regulate expression of the two molecules are, in part, distinct: both cytokines increase the transcriptional rate of the encoding genes, whereas only IL-2 acts also at a post-transcriptional level to increase the stability of their mRNA.
Characteristics of endogenous peptides eluted from the class I MHC molecule HLA-B7 determined by mass spectrometry and computer modeling.
Authors: Huczko E L , Bodnar W M , Benjamin D , Sakaguchi K , Zhu N Z , Shabanowitz J , Henderson R A , Appella E , Hunt D F , Engelhard V H 
Published: December 2022

Abstract
Microcapillary HPLC electrospray ionization tandem mass spectrometry was used to sequence 15 peptides eluted from HLA-B7. Sequence alignment implicated four peptide positions in specific interactions with the class I molecule, and their importance was confirmed using synthetic peptides. Because no crystal structure for HLA-B7 was available, computer-assisted modeling was used to understand novel aspects of peptide binding specificity and to accurately predict the effect of defined changes in peptide structure. The results demonstrate that mass-spectrometric sequencing coupled with computer-assisted modeling can be used in the absence of a crystal structure to make accurate predictions concerning requirements for peptide binding to class I molecules. These techniques may be valuable to predict or engineer T cell epitopes.
Coordinate silencing of myeloma-specific genes in myeloma x T lymphoma hybrids.
Authors: Lieberman S A , Hines M D , Bergsagel P L , Kuehl W M , Eckhardt L A 
Published: December 2022

Abstract
It has been well-established that Ig genes are transcriptionally silenced when Ig-producing myeloma lines are fused to non-B cells. In the present study, we analyzed the expression of several other myeloma-specific genes in fusions of myelomas with the T lymphoma, BW5147. Seven of the eight genes analyzed behaved coordinately with the Ig loci; they were silent in most myeloma x T hybrids but active in the rare hybrid that retained Ig gene expression. Cloned IgH genes introduced into the two types of hybrids behaved as their endogenous counterparts. The coordinate behavior of these several genes in the panel of "exceptional" and "extinguished" hybrids suggests a central and bimodal switch for alternately activating and de-activating the genetic program of the Ig-secreting plasmacyte. The switch between an active and an inactive transcriptional state involves, at some level, a change in the methylation status of the IgH genes. Methylation and transcriptional activity were inversely correlated. In Ig-extinguished hybrids the myeloma-derived locus was methylated de novo, whereas in the rare Ig-expressing hybrid, the T cell-derived locus was demethylated de novo.