bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the Presence of Heterophile (Forssman's) Antigen in Bacteria of the Paratyphoid-Dysentery Group
Authors: Jungeblut Claus W. , Ross Alexander T. 
Published: December 2022

Summary
Immunization of rabbits with certain strains of B. dysenteriae Shiga or B. paratyphosus B was followed with great regularity by the appearance in the serum of hemolysins active for sheep and goat red corpuscles, but inactive for those of the human or rabbit. No formation of hemolysins was noted by immunizing guinea pigs with the same cultures. Hemolytic Shiga and paratyphoid B sera fixed complement specifically in the presence of true Forssman antigen. The heterophile antibodies in Shiga and paratyphoid B sera were completely and specifically absorbed by contact with their homologous bacterial antigens as well as by absorption with true Forssman antigen. Intravenous injection of Shiga and paratyphoid B sera into guinea pigs was only occasionally followed by a characteristic systemic reaction due to primary antiserum toxicity. Intracutaneous injection of Shiga and paratyphoid B sera into white guinea pigs and dogs induced frequently a well defined local, inflammatory reaction of the allergic type, particularly in the case of the latter sera. Complement fixation between true Forssman antisera and Shiga or paratyphoid B bacilli as the respective antigens was not readily demonstrable. The reactions were only faint and occurred irregularly. Absorption of true Forssman antisera by Shiga or paratyphoid B bacilli caused no definite loss of heterophile hemolysins in such sera. No evidence was found for the presence of heterophile antigen in strains of B. paradysenteriae (Flexner), B. paratyphosus A and B. enteritidis (Gaertner).
Antibody Studies in Serum Sickness
Authors: Tuft Louis , Ramsdell Susan Griffith 
Published: December 2022

Summary
The general findings of Longcope and Rackemann, as to the presence of circulating antibodies following serum disease and their absence following treatment with antisera without serum disease, have been confirmed by this study. In addition, we have shown that antibody content is conditioned by the intensity of the disease and by the interval after the onset of the disease at which the bleeding is made; that anaphylactic antibody is more regularly present than has been previously indicated; that the positive Prausnitz-Küstner reaction may be demonstrated in a large proportion of cases; and that the passive sensitization of the guinea pig ear-skin could be regularly induced.
A definite relationship between the antibody responsible for the Prausnitz-Küstner reaction and the basic mechanism of serum disease is not clear; our results indicate no more than that this antibody occurs as one phase of a general stimulation of the various antibodies, initiated by a cellular reaction to the presence of a foreign serum; that it differs from an atopic reagin, in its experimental manifestations, only in that it persists in the serum of the patient but for a short time; and that the finding of this antibody in serum disease sera may be regarded as an instance of reagin production to a typical atopen in non-atopic individuals.
Cutting Edge: CD40 Engagement Up-Regulates Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Human Lung Fibroblasts
Authors: Zhang Ying , Cao H. James , Graf Beth , Meekins Heather , Smith Terry J. , Phipps Richard P. 
Published: December 2022

Abstract
A newly emerging view of fibroblasts is that they are vital for initiating inflammation and respond to and direct the activities of leukocytes. Human fibroblasts can express CD40, an activation Ag the ligand of which is displayed by activated leukocytes. We demonstrate here that CD40 engagement on human lung fibroblasts dramatically increases proinflammatory PGE2 synthesis. This up-regulation is mediated through an induction of cyclooxygenase-2 (Cox-2) since Cox-2-selective inhibitors block the up-regulation. Western and Northern blot analyses demonstrated that Cox-2 protein and mRNA are dramatically increased in fibroblasts following CD40 engagement. We conclude that CD40 is a major pathway in human fibroblasts for the induction of Cox-2. There is intense interest in devising strategies for disruption of the CD40-CD40 ligand system to blunt inflammation. Such an intervention would be expected to attenuate the up-regulation of fibroblast Cox-2 and PGE2 production at the site of tissue injury.
Avoidance of Self-Reactivity Results in Skewed CTL Responses to Rare Components of Synthetic Immunogens
Authors: Purcell Anthony W. , Chen Weisan , Ede Nicholas J. , Gorman Jeffrey J. , Fecondo John V. , Jackson David C. , Zhao Yuming , McCluskey James 
Published: December 2022

Abstract
In studying the CTL recognition of peptide determinants derived from the nuclear Ag La (SS-B), we observed significant skewing of the response toward rare components present within the immunogen. Thus, priming of naive mouse lymphocytes in vitro with a synthetic H-2Kb-binding peptide comprising human La (hLa) residues 51–58 resulted in class I-restricted cytotoxic T cells that failed to recognize naturally presented hLa 51–58 peptide. Instead, the majority of T hybrids recognized a low abundance (≤1%) contaminant present at picomolar concentrations in the original synthesis and identified as a peptide adduct containing N,4-t-butyl asparagine at position 6 of the hLa 51–58 sequence. The preferred T cell recognition of the butyl adduct was not due to increased affinity of this peptide for the H-2Kb molecule or to the antagonism of CTL recognizing the unmodified determinant. Rather, the bias in the immune response appeared to be the result of partial self-tolerance to the homologous mouse La 51–58 determinant, which differs from its human counterpart by only a single amino acid at position 1 (T→I). Accordingly, the CTL response appeared to be focused on “non-self” ligands present within the synthesis, even though they were present at very low concentrations. These observations have significant implications for the use of synthetic peptide vaccines, especially those designed to manipulate responses to self peptides such as tumor Ags in which self-tolerance may result in unexpected reactivity.
A Fusion of the EBV Latent Membrane Protein-1 (LMP1) Transmembrane Domains to the CD40 Cytoplasmic Domain Is Similar to LMP1 in Constitutive Activation of Epidermal Growth Factor Receptor Expression, Nuclear Factor-κB, and Stress-Activated Protein Kinase
Authors: Hatzivassiliou Eudoxia , Miller William E. , Raab-Traub Nancy , Kieff Elliott , Mosialos George 
Published: December 2022

Abstract
The EBV latent infection transforming protein, LMP1, has six hydrophobic transmembrane domains that enable it to aggregate in the plasma membrane and a 200-amino acid carboxyl-terminal cytoplasmic domain (CT) that activates nuclear factor-κB and induces many of the phenotypic changes in B lymphocytes that accompany CD40 activation. Since the phenotypic effects of LMP1 are similar to those of activated CD40, we now compare signaling from the LMP1 CT with that from the CD40 CT fused to the LMP1 transmembrane domains. The LMPCD40 chimera was similar to LMP1 in nuclear factor-κB activation and in up-regulation of epidermal growth factor receptor expression. CD40 ligation was known to activate the stress-activated protein kinase, and both LMPCD40 and LMP1 are now shown to induce stress-activated protein kinase activity in the absence of ligand. Deletion of the first four transmembrane domains of LMP1 abrogated LMP1 aggregation in the plasma membrane and nearly abolished signaling from LMP1 or the LMPCD40 chimera. These results highlight the role of LMP1 as a constitutively active receptor similar to CD40 and provide a novel approach for the generation of ligand-independent receptors.
Autologous Human Monocyte-Derived Dendritic Cells Genetically Modified to Express Melanoma Antigens Elicit Primary Cytotoxic T Cell Responses In Vitro: Enhancement by Cotransfection of Genes Encoding the Th1-Biasing Cytokines IL-12 and IFN-α
Authors: Tüting Thomas , Wilson Cara C. , Martin Dina M. , Kasamon Yvette L. , Rowles Jennifer , Ma Debora I. , Slingluff Craig L. , Wagner Stephan N. , van der Bruggen Pierre , Baar Joseph , Lotze Michael T. , Storkus Walter J. 
Published: December 2022

AbstractDNA-based immunization strategies designed to elicit cellular antitumor immunity offer an attractive alternative to protein- or peptide-based approaches. In the present study we have evaluated the feasibility of DNA vaccination for the induction of CTL reactivity to five different melanoma Ags in vitro. Cultured, monocyte-derived dendritic cells (DC) were transiently transfected with plasmid DNA encoding human MART-1/Melan-A, pMel-17/gp100, tyrosinase, MAGE-1, or MAGE-3 by particle bombardment and used to stimulate autologous PBMC responder T cells. CTL reactivity to these previously identified melanoma Ags was reproducibly generated after two or three stimulations with genetically modified DC. Co-ordinate transfection of two melanoma Ag cDNAs into DC promoted CTL responders capable of recognizing epitopes from both gene products. Coinsertion of genes encoding the Th1-biasing cytokines IL-12 or IFN-α consistently enhanced the magnitude of the resulting Ag-specific CTL reactivity. Importantly, DC transfected with a single melanoma Ag cDNA were capable of stimulating Ag-specific CTL reactivity restricted by multiple host MHC alleles, some of which had not been previously identified. These results support the inherent strengths of gene-based vaccine approaches that do not require prior knowledge of responder MHC haplotypes or of relevant MHC-restricted peptide epitopes. Given previous observations of in situ tumor HLA allele-loss variants, DC gene vaccine strategies may elicit a greater diversity of host therapeutic immunity, thereby enhancing the clinical utility and success of such approaches.
CD4+CD25+ T Cells Inhibit Both the Induction and Effector Function of Autoreactive T Cells and Represent a Unique Lineage of Immunoregulatory Cells
Authors: Suri-Payer Elisabeth , Amar Anna Z. , Thornton Angela M. , Shevach Ethan M. 
Published: December 2022

AbstractThymectomy of susceptible strains of mice on day 3 of life results in a spectrum of organ-specific autoimmunity that can be prevented by reconstitution of the thymectomized animals early in life with normal adult lymphocytes. The effectors and suppressors of autoimmunity in this model have been convincingly shown to be CD4+ T cells. It has been demonstrated recently that the regulatory CD4+ T cells that prevent disease coexpress CD25. We have further characterized the population of CD4+CD25+ immunoregulatory cells and demonstrated that they can suppress not only the induction of disease post-thymectomy, but can also efficiently suppress disease induced by cloned autoantigen-specific effector cells. Furthermore, the CD4+CD25+ T cells appear to be members of a unique lineage of regulatory T cells, as the induction of CD25 expression on a monospecific population of T cells derived from TCR transgenic SCID mice did not result in suppression of post-thymectomy autoimmunity. In addition, the TCR transgenic SCID mice were highly susceptible to autoimmune disease induced by the cloned line of autoantigen-specific effectors, while normal mice were relatively resistant. The capacity of the cloned line to transfer disease to nu/nu recipients could be inhibited by normal spleen cell populations containing CD4+CD25+ cells and by purified CD4+CD25+ cells. Although the target Ag(s) and mechanism of action of the CD4+CD25+ T cells remain to be determined, it is likely that they also play an important role in modulating other autoimmune diseases that are mediated by activation of “ignorant” self-reactive T cells present in the normal peripheral lymphocyte pool.
In Vitro Comparison of the Biologic Activities of Monoclonal Monomeric IgA, Polymeric IgA, and Secretory IgA
Authors: Renegar Kathryn B. , Jackson Graham D. F. , Mestecky Jiri 
Published: December 2022

Abstract
Secretory IgA (S-IgA), a major humoral mediator of mucosal immunity, is a polymeric Ig containing an unusual extra polypeptide, secretory component (SC), added during transcytosis through epithelial cells. Polymeric S-IgA is more effective than monomeric IgA (mIgA) and IgG in neutralizing viruses. It is not known whether this increased efficacy is due solely to the polymeric structure of the molecule or whether SC itself makes S-IgA more efficient; a quantitative in vitro comparison of the biologic activities of S-IgA and pIgA has not been reported. We prepared purified pIgA and mIgA mAbs directed toward the H1 hemagglutinin of PR8 influenza virus and purified monoclonal S-IgA (made from monoclonal pIgA injected into a Lewis rat and collected as S-IgA from bile) and compared their abilities to carry out hemagglutination inhibition (HI) and neutralization of the infectivity of PR8 influenza virus in vitro. The polymeric Igs (pIgA and S-IgA) were 5 times more effective than mIgA in HI and 7 to 10 times more effective than mIgA in virus neutralization. Addition of SC to pIgA did not modify its ability to mediate HI and had only a minimal effect (S-IgA was 1.4 times more effective) on its ability to neutralize influenza virus in vitro. Trypsin preincubation partially abolished mIgA- or pIgA-mediated, but not S-IgA-mediated, viral neutralization. Thus, although S-IgA is more stable functionally than pIgA, the addition of SC does not influence, positively or negatively, the biologic activity associated with the Fab of S-IgA.
Structure, Diversity, and Repertoire of VH Families in the Mexican Axolotl
Authors: Golub Rachel , Charlemagne Jacques 
Published: December 2022

AbstractThe Mexican axolotl VH segments associated with the Igh Cμ and Cυ isotypes were isolated from anchored PCR libraries prepared from spleen cell cDNA. The eight new VH segments found bring the number of VH families in the axolotl to 11. Each VH had the canonical structural features of vertebrate VH segments, including residues important for the correct folding of the Ig domain. The distribution of ser AGC/T (AGY) and TCN codons in axolotl VH genes was biased toward AGY in complementarity-determining region-1 (CDR1) and TCN in framework region-1 (FR1); there were no ser residues in the FR2 region. Thus, the axolotl CDR1 region is enriched in DNA sequences forming potential hypermutation hot spots and is flanked by DNA sequences more resistant to point mutation. There was no significant bias toward AGY in CDR2. Southern blotting using family-specific VH probes showed restriction fragments from 1 (VH9) to 11–19 (VH2), and the total number of VH genes was 44 to 70, depending on the restriction endonuclease used. The VH segments were not randomly used by the Hμ and Hυ chains; VH1, VH6, and VH11 were underutilized; and the majority of the VH segments belonged to the VH7, VH8, and VH9 families. Most of the nine JH segments seemed to be randomly used, except JH6 and JH9, which were found only once in 79 clones.
Eosinophils Bind Rhinovirus and Activate Virus-Specific T Cells
Authors: Handzel Zeev T. , Busse William W. , Sedgwick Julie B. , Vrtis Rose , Lee Wai Ming , Kelly E. A. B. , Gern James E. 
Published: December 2022

AbstractEpisodes of virus-induced exacerbations of asthma are accompanied by increased eosinophils (EOS) in respiratory secretions and evidence of EOS degranulation. Although rhinoviruses (RV) are the viruses most often implicated in exacerbations of asthma in both children and adults, little is known about the immune response to this group of viruses and, in particular, EOS-RV interactions. To define such interactions, we incubated human rhinovirus type 16 (RV16), a serotype using ICAM-1 as a receptor, with EOS purified from PBMC, and measured EOS-RV binding, EOS-mediated Ag presentation and T cell activation, and EOS cell surface marker expression and superoxide production. Significant RV16 binding occurred to EOS that were pretreated with granulocyte-macrophage CSF, and this binding was inhibited by anti-ICAM-1 mAb. EOS also presented viral Ags to RV16-specific T cells, causing T cell proliferation and secretion of IFN-γ. RV16 induced a significant shift from CD18dim to CD18bright, but did not affect EOS expression of CD54, CD69, or HLA-DR. Finally, RV16 did not induce superoxide production from peripheral blood EOS. These findings suggest that RV16 also binds to airway EOS, which resemble granulocyte-macrophage CSF-treated blood EOS in terms of high expression of ICAM-1. Furthermore, our findings suggest that EOS could participate in RV-induced immune responses through Ag presentation and T cell activation. By activating RV-specific T cells, EOS may play an important role in the initiation of antiviral T cell responses, and these effects could also contribute to enhanced airway inflammation and increased asthma symptoms in susceptible individuals.
Protective Effect onLeishmania majorInfection of Migration Inhibitory Factor, TNF-α, and IFN-γ Administered Orally via AttenuatedSalmonella typhimurium
Authors: Xu Damo , McSorley Stephen J. , Tetley Lawrence , Chatfield Stephen , Dougan Gordon , Chan W. Ling , Satoskar Abhay , David John R. , Liew Foo Y. 
Published: December 2022

AbstractThe genes encoding murine macrophage migration inhibitory factor (MIF), IL-2, IFN-γ or TNF-α were cloned individually into an expression plasmid under the control of the inducible promoter nirB and transfected into the aroA−aroD− deletion mutant strain of Salmonella typhimurium (BRD509). These S. typhimurium derivatives (henceforward called constructs and termed GIDMIF, GIDIL2, GIDIFN and GIDTNF) expressed their respective cytokines in vitro under anaerobic conditions and stably colonized BALB/c mice up to 14 days after oral administration. The highly susceptible BALB/c mice that had received the constructs orally and that had been subsequently infected via the footpad with Leishmania major, developed significantly reduced disease compared with control mice administered the untransfected Salmonella strain (BRD509). Importantly, a combination of GIDMIF, GIDIFN, and GIDTNF administered orally after L. major infection was able to significantly limit lesion development and reduced parasite loads by up to three orders of magnitude. Spleen and lymph node cells of mice administered this combination expressed markedly higher levels of inducible nitric oxide synthase (iNOS) compared with those from mice receiving an equivalent dose of the control strain of Salmonella (BRD509). These data therefore demonstrate the feasibility of therapeutic treatment in an infectious disease model using cytokines delivered by attenuated Salmonella. The protective effect observed correlates with the induction of inducible nitric oxide synthase in vivo.
Activation of Mitogen-Activated Protein Kinase Pathways byMycoplasma fermentansMembrane Lipoproteins in Murine Macrophages: Involvement in Cytokine Synthesis
Authors: Rawadi Georges , Ramez Valerie , Lemercier Brigitte , Roman-Roman Sergio 
Published: December 2022

AbstractStimulation of monocytes and resident macrophages by mycoplasmas induces production of numerous cytokines. We have previously reported that membrane lipoproteins derived from Mycoplasma fermentans are responsible for the induction of proinflammatory cytokines by monocytic cells and that triggering protein tyrosine kinase activation is an essential requirement for this biologic effect. In the present study, we have investigated the effect of M. fermentans-derived membrane lipoproteins (LAMPf) on mitogen-activated protein kinase (MAPK) cascades in the murine macrophage cell line RAW 264.7 and have analyzed the contribution of these pathways to the cytokine induction mediated by this agent. Treatment of murine macrophages with LAMPf resulted in significant activation of MAPK family members extracellular signal-regulated kinase 1 and 2 (ERK1/2), c-Jun NH2-terminal kinase (JNK), and p38. Unlike LPS, these effects were demonstrated to be independent of the presence of serum. The activation of MAPKs paralleled the tyrosine kinase activation and peaked at 30 min after stimulation. The specific p38 inhibitor SB203580 abrogated the mycoplasma-induced IL-6, IL-1β, and TNF-α synthesis. The selective MAPK/extracellular signal-regulated kinase 1 (MEK-1) inhibitor PD-98059 blocked both IL-1β and TNF-α but not IL-6 production by RAW 264.7 cells in response to LAMPf. Additionally, transfection of murine macrophages with a JNK dominant negative mutant significantly reduced only IL-6 production. These data underscore the role of MAPKs as signal transduction molecules controlling the expression of cytokines upon mycoplasma stimulation.
Activation of Protein Kinase C-ζ and Phosphatidylinositol 3′-Kinase and Promotion of Macrophage Differentiation by Insulin-Like Growth Factor-I
Authors: Liu Qiang , Ning Wei , Dantzer Robert , Freund Gregory G. , Kelley Keith W. 
Published: December 2022

AbstractPhosphoinositides that are phosphorylated at the D3 position have been reported to activate an atypical, Ca2-independent protein kinase C (PKC) isoform designated PKC-ζ, and overexpression of this enzyme leads to monocytic differentiation. In this study, we cultured human HL-60 promyeloid cells with vitamin D3 and insulin-like growth factor-I (IGF-I), a 70-amino-acid peptide that activates phosphatidylinositol 3′-kinase (PI 3-kinase) in murine promyeloid cells. Two days later, the proportion of cells differentiating into macrophages in serum-free medium, as assessed by expression of the α-subunit of the β2 integrin CD11b, increased from 5 ± 1% to 25 ± 3%. Addition of IGF-I increased the proportion of cells differentiating into CD11b-positive macrophages to 78 ± 5%. In the absence of vitamin D3, IGF-I did not induce expression of CD11b (6 ± 1%). The IGF-I-promoted macrophage differentiation was blocked specifically by preincubation of HL-60 cells with a mAb (αIR3) directed against the IGF type I receptor. Similarly, pretreatment of cells with either αIR3 or an IGF-binding protein, IGFBP-3, led to a 75% inhibition of CD11b expression when cells were cultured with vitamin D3 in serum-containing medium. IGF-I, but not vitamin D3, caused a sevenfold increase in the enzymatic activity of both PI 3-kinase and atypical PKC-ζ. Inhibition of IGF-I-inducible PI 3-kinase with either wortmannin or LY294002 abrogated the IGF-I-induced activation of PKC-ζ and totally blocked the enhancement in macrophage differentiation caused by IGF-I. These data establish that PKC-ζ is a putative downstream target of PI 3-kinase that is activated during IGF-I-promoted macrophage differentiation.