bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attenuation of IL-5-mediated signal transduction, eosinophil survival, and inflammatory mediator release by a soluble human IL-5 receptor.
Authors: Monahan J , Siegel N , Keith R , Caparon M , Christine L , Compton R , Cusik S , Hirsch J , Huynh M , Devine C , Polazzi J , Rangwala S , Tsai B , Portanova J 
Published: December 2022

Abstract
A soluble form of the human IL-5R alpha-chain (IL-5Ra) that contains the extracellular IL-5 binding domain has been evaluated for its effect on IL-5 binding to and activation of human eosinophils and basophils. The truncated receptor was expressed in Escherichia coli and recovered in biologically active form following renaturation and anion exchange chromatography. The soluble receptor formed a 1/1 complex with IL-5 in solution and bound IL-5 with affinity comparable to that of cell-associated IL-5Ra. Soluble IL-5Ra also competed with IL-5 for binding to the native alpha beta IL-5R on human cells and inhibited IL-5-mediated receptor activation and inflammatory mediator production. In this regard, the soluble receptor prevented IL-5-induced tyrosine phosphorylation of JAK2 kinase and IL-5R beta-chain and inhibited IL-5 priming of leukotriene C4 release by human basophils. However, the E. coli-derived receptor failed to inhibit IL-5 in longer term assays, including eosinophil survival and TF-1 cell proliferation, possibly due to its propensity to aggregate in a time- and temperature-dependent manner. In contrast, we observed that a soluble IL-5Ra derived from baculovirus-infected cells was less prone to aggregate and effectively antagonized IL-5-induced cell proliferation and survival. These findings indicate that the extracellular portion of the human IL-5Ra chain can prevent association of IL-5 with cell surface receptors and can attenuate signal transduction, mediator release, and survival of inflammatory cells. As such, soluble IL-5R may be useful in treating diseases such as human asthma, in which pulmonary injury is associated with the activity of IL-5R-bearing cells.
Depletion of CD8+ T lymphocytes by murine monoclonal CD8 antibodies and restored specific T cell proliferation in vivo in a patient with chronic hepatitis C.
Authors: Kiefersauer S , Reiter C , Eisenburg J , Diepolder H M , Rieber E P , Riethmüller G , Gruber R 
Published: December 2022

Abstract
Cellular immune mechanisms, especially those mediated by CD8+ T cells, are important in the pathogenesis and control of viral infections. On the other hand, as shown for chronic lymphocytic choriomeningitis virus infection in the mouse, CD8+ T cells may not only hinder the elimination of a virus, but make the host unresponsive to a second viral infection. In hepatitis C virus (HCV) infections, at least 50% of the patients become chronically infected, despite the detection of HCV-specific CTL and a specific proliferative response to HCV Ags in PBL and in lymphocytes isolated from the liver. To better understand the immunopathologic mechanisms of CD8+ cells in vivo and to search for a potential treatment, we applied murine CD8 mAbs to a patient with therapy-resistant chronic HCV. A drastic reduction of CD8+ circulating lymphocytes, a reduction of CD8 molecule density, and complement fixation on CD8+ cells were observed. The reduction of CD8+ cells was compensated partially by an elevation of CD4+ cells. High concentrations of neutralizing human anti-mouse Abs were induced. After the Ab infusions, the CD4/CD8 ratio in peripheral blood increased from 1.6 to values of about 3 during therapy, and gradually decreased to 2.3 1 yr after the last mAb infusion. A continuing decrease of serum aminotransferases and clinical improvement was observed. Interestingly, after initiation of treatment, a significant proliferative response to HCV-specific Ags became measurable.
Activation of monocytes by HIV-Tat treatment is mediated by cytokine expression.
Authors: Lafrenie R M , Wahl L M , Epstein J S , Yamada K M , Dhawan S 
Published: December 2022

Abstract
Treatment of primary monocytes with soluble HIV-Tat protein is associated with increased monocyte metalloproteinase-9 (MMP-9) expression and enhanced beta 2 integrin expression that increases monocyte/endothelial adhesion. These alterations require greater than 12 h of HIV-Tat treatment, suggesting the involvement of intermediate factors. Thus, we have examined the role of cytokines in the HIV-Tat-induced alteration of monocyte function. Treatment of monocytes with HIV-Tat rapidly up-regulated the production of IL-1 beta, IL-6, IL-8, and TNF-alpha, but not IL-3, granulocyte-macrophage CSF, basic fibroblast growth factor, or macrophage-inflammatory protein-1 alpha, and was associated with up-regulation of the corresponding cytokine mRNA. Inclusion of neutralizing anti-cytokine Abs to IL-1 beta or TNF-alpha during the HIV-Tat pretreatment period significantly inhibited the HIV-Tat-induced increase in MMP-9 production, monocyte/endothelial adhesion, and monocyte-dependent endothelial damage. In contrast, neutralizing Abs against IL-6 and IL-8 had no effect. The effects of HIV-Tat treatment, namely MMP-9 production, enhanced monocyte/endothelial cell adhesion, and monocyte-dependent endothelial damage, were mimicked by treating the monocytes with IL-1 beta or TNF-alpha, but not with IL-6 or IL-8. Therefore, the mechanism by which HIV-Tat activates monocyte function is dependent on HIV-Tat-induced production of cytokines (IL-1 beta and TNF-alpha).
Experimental Inoculation of Chickens with Hodgkin's Nodes
Authors: L'Esperance Elise S. 
Published: December 2022

Summary and Conclusions
Five healthy chickens were inoculated intravenously with emulsions of lymph nodes from two cases of clinically and histologically characteristic Hodgkin's disease.
All of these chickens developed either a typical, or an atypical tuberculosis, and in the tissue smears, stained by Ziehl-Neelsen method, acid-fast granules and rods, extra- and intra-cellular, were demonstrated in three of them, and non-acid-fast granules in one of them.
Reinoculation of material from the lesions of one of these chickens into another chicken produced an identical, though more extensive manifestation of the disease.
An atypical tuberculosis developed in guinea pigs by inoculation of the tissue from the fourth chicken. A growth of bacteria with the staining and cultural characteristics of the avian tubercle bacillus was produced on egg media from material from this guinea pig.
Cultures from these birds on egg media were contaminated in all instances. In one, the chicken culture gave a symbiotic growth of a blastomyces like organism with an acid fast bacillus. These cultures were reinoculated into normal chickens and guinea pigs, but sufficient time has not elapsed to determine the results of this reinoculation.
While it is recognized that the two short series of experiments here reported cannot quite exclude the apparently unlikely alternative explanation, that we were dealing with an accidental avian infection, the findings seem to justify the conclusion that in these chickens, a lesion with the histological features of Hodgkin's granuloma, and comparable to avian tuberculosis has been produced after the inoculation of emulsified Hodgkin's nodes. This may indicate that the etiological agent in certain forms of Hodgkin's disease is pathogenic for birds, or that the avian tubercle bacilli are a factor in producing some of the lesions which are interpreted as Hodgkin's disease.
Heterogeneity of Streptococci Isolated from Sputum
Authors: Hooker Sanford Burton , Anderson Lillian M. , Follensby Edna M. , Force Helen V. , Tayian Elizabeth H. 
Published: December 2022

Summary
Non-hemolytic streptococci of the alpha type are the dominant aërobic flora in sputa from minor respiratory infections. The common fermentative types in order of decreasing frequency are salivarius, mitis, and ignavus. Many sub-groups exist. Hemolytic streptococci of the true beta type are uncommonly found in these sputa. Their presence is but temporary and seems dependent upon the epidemic prevalence of certain respiratory infections. Fermentative groups are less numerous; the pyogenes type is outstanding. Alpha prime varieties have a similarly fluctuating and infrequent incidence. Gamma types are often present but rarely predominate. There is considerable fermentative diversity among strains of these two types. When many colonies of the dominant type and of indistinguishable appearance are selected from a primary plate, they can usually be separated, on the basis of other physiological characteristics, into several distinct groups. This peculiar heterogeneity has been studied in connection with 2057 colony strains from 101 specimens. Of the collections of strains isolated from virtually open surfaces about 85 per cent were diverse assemblages; those derived from closed foci or from entitative disease were homogeneous in 19 of 20 instances. The literature has been reviewed for evidence as to the homogeneity or heterogeneity of an individual's strains of streptococci and other genera. The more recent literature on the antigenic properties of alpha streptococci is reviewed and certain technologic aspects of serological classifications are critically discussed. Cross-agglutination and fixation tests have demonstrated a bewildering antigenic heterogeneity among alpha streptococci; strong cross-agglutination was observed in less than 3 per cent of 616 tests. No identical strains, from different sources, were discovered. Group reactions occurred among fermentative heterologs as well as among strains of the same fermentative type. Antigenic unlikeness also features the identical-colony strains derived from individuals. Consideration is given to the pertinent bearing which this heterogeneity has upon autogenous vaccine treatment and upon the classification of non-hemolytic streptococci.
Experimental Studies with Pyocyaneus Filtrates
Authors: Oesterlin Ernst J. 
Published: December 2022

Summary
Percutaneous or intraperitoneal previous treatment with pyocyaneus filtrates protect neither guinea pigs nor rabbits from a respectively subcutaneous or intraperitoneal infection with Bacillus pyocyaneus. It is possible to protect both kinds of animals by repeated intrapleural injections of previously heated pyocyaneus filtrate against intrapleural infection with Bacillus pyocyaneus. The resistance acquired in this way is restricted to the pleural cavity. Simultaneous metastatic infections of the liver and of the kidney are common findings. In other cases the resistance is only a relative one; in spite of the previous treatment an infection of the pleura occurs, but the course of the disease is much slower than in the control animals. The question of specificity of the action of the filtrates will be studied on a larger scale. Although an occasional increase of resistance caused by the unspecific filtrates has been found, the protection produced by specific filtrates seems to be more intense and more dependable. Intrapleural injections with sterile broth have no prophylactic value against an intrapleural infection with Bacillus pyocyaneus: it is impossible to protect the animals by broth injections against such infections.
Follicular Dendritic Cell (FDC) Precursors in Primary Lymphoid Tissues
Authors: Kapasi Zoher F. , Qin Dahui , Kerr William G. , Kosco-Vilbois Marie H. , Shultz Leonard D. , Tew John G. , Szakal Andras K. 
Published: December 2022

AbstractThe origin of follicular dendritic cells (FDC) is unresolved, and as such, remains controversial. Based on the migration of Ag-transporting cells (ATC) into lymphoid follicles and the phenotypic similarity between FDC and ATC, one hypothesis is that ATC may represent emigrating FDC precursors. This contrasts with the view that FDC originate from local stromal cells in the secondary lymphoid tissues. Mice homozygous for the severe combined immunodeficiency (prkdcscid) mutation (scid) lack FDC. Thus, they provide a powerful tool for assessing de novo generation of FDC. To test whether FDC precursors could be found in bone marrow or fetal liver, scid/scid mice were reconstituted with either: 1) bone marrow cells from (BALB/c × C57BL/6)F1 donors, 2) bone marrow cells from ROSA BL/6 F1 (lacZ-transfected) mice, 3) rat bone marrow cells, or 4) rat fetal liver cells. Six to eight weeks after reconstitution with F1 bone marrow, cells reactive with the FDC-labeling mAb, FDC-M1, also expressed donor class I molecules on their surfaces. Similarly in mice reconstituted with lacZ-transfected bone marrow cells, these cells were also positive for the lacZ gene product. Furthermore, in spleens of animals reconstituted with either rat bone marrow or rat fetal liver, rat FDC were identified using the specifically labeling mAb, ED5. In all cases, host FDC were also present, indicating that scid/scid mice have FDC precursors that will mature in the presence of allogeneic or xenogeneic lymphoid cells. In summary, FDC can be derived from progenitor cells present in primary lymphoid tissues.
IL-12 Up-Regulates CD40 Ligand (CD154) Expression on Human T Cells
Authors: Peng Xiaohui , Remacle Jacques E. , Kasran Ahmad , Huylebroeck Danny , Ceuppens Jan L. 
Published: December 2022

AbstractIL-12 is a heterodimeric cytokine produced by APC that promotes the development of CD4+ Th1 cells and their IFN-γ production after TCR/CD3 triggering. We here investigated the capacity of IL-12 to modify the expression on T cells of CD40 ligand (CD40L or CD154), a molecule transiently expressed on activated T cells and known to be of utmost importance for cognate interaction with B cells and for activation of dendritic cells and macrophages. Our data demonstrate that IL-12 up-regulates CD40L expression on anti-CD3-activated human peripheral blood T cells. For optimal induction of CD40L, IL-12 synergizes with IL-2 as well as with other costimulatory interactions, such as B7/CD28. The effect of IL-12 was observed at both the protein and the mRNA level. T cells costimulated by IL-12 provided more efficient help for IL-4-dependent B cell proliferation and for IgG production than when activated in the absence of IL-12. This helper activity was blocked by an mAb against CD40L, indicating that the effect of IL-12 on B cells is mediated indirectly through CD40L. The data thus suggest that the effects of IL-12 on cellular and humoral immune responses are partly mediated through CD40L induction.
An Intronic Silencer Regulates B Lymphocyte Cell- and Stage-Specific Expression of the Human Complement Receptor Type 2 (CR2, CD21) Gene
Authors: Makar Karen W. , Pham Christine T. N. , Dehoff Marlin H. , O’Connor Siobhan M. , Jacobi Susan M. , Holers V. Michael 
Published: December 2022

AbstractHuman CR2 (CD21) is a B lymphocyte protein whose surface expression is restricted primarily to the mature cell stage during development. To study the transcriptional mechanisms that govern cell- and stage-restricted CR2 expression, we first performed transient transfection analysis using constructs extending from −5 kb to +75 bp (−5 kb/+75) in the CR2 promoter. The promoter was found to be broadly active, with no evidence of cell- or stage-specific reporter gene expression. However, the addition of a 2.5-kb intronic gene segment (containing a DNase I hypersensitive site) to the (−5-kb/+75) construct resulted in appropriate reporter gene expression, defined as the silencing of the (−5-kb/+75) promoter activity only in non-CR2-expressing cells. Interestingly, appropriate reporter gene expression required stable transfection of the constructs in cell lines, suggesting nuclear matrix or chromatin interactions may be important for appropriate CR2 gene expression. Importantly, transgenic mice also required the intronic silencer to generate lymphoid tissue-specific reporter gene expression. Some transgenic founder lines did not demonstrate reporter gene expression, however, indicating that additional transcriptional regulatory elements are present in other regions of the CR2 gene. In summary, these data support the hypothesis that human CR2 expression is regulated primarily by an intronic silencer with lineage- and B cell stage-specific activity.
Internalization of Chlamydia by Dendritic Cells and Stimulation of Chlamydia-Specific T Cells
Authors: Ojcius David M. , Bravo de Alba Yolanda , Kanellopoulos Jean M. , Hawkins Ray A. , Kelly Kathy A. , Rank Roger G. , Dautry-Varsat Alice 
Published: December 2022

Abstract
Chlamydia species are the causative agents of trachoma, various forms of pneumonia, and the most common sexually transmitted diseases. Although the infection cycle has been extensively characterized in epithelial cells, where the Chlamydia entry-vacuoles avoid fusion with host-cell lysosomes, the cellular immune response has received less attention. Moreover, despite the abundant presence of dendritic cells (DC) in the sites of infection, the interaction between Chlamydia and DC has never been studied. We observe that DC kill Chlamydia trachomatis and Chlamydia psittaci. The chlamydiae are internalized by the DC in a nonspecific manner through macropinocytosis, and the macropinosomes fuse subsequently with DC lysosomes expressing MHC class II molecules. The interaction induces maturation of the DC, since presentation of an exogenous Ag is severely inhibited after a 1-day incubation, although chlamydial Ags are still presented and recognized by Chlamydia-specific CD4+ T cells. Thus, DC most likely play a role in initiating the T cell response in vivo and could potentially be used in adoptive transfer therapies to vaccinate against Chlamydia.
Induction of Pulmonary Allergic Responses by Antigen-Specific Th2 Cells
Authors: Li Xiu-Min , Schofield Brian H. , Wang Qian-Fei , Kim Kawn-Hyoung , Huang Shau-Ku 
Published: December 2022

AbstractThe development of pulmonary allergic responses was examined in mice following pulmonary transfer of Ag (conalbumin)-specific Th2 cells. The levels of serum-specific IgE, cellular infiltrates, airway mucus goblet cells, and airway responsiveness were analyzed and compared with those in Ag-sensitized and -challenged mice. Pulmonary transfer of the conalbumin-specific Th2 clone (D10) induced, in an Ag-specific manner, high levels of the Th2 cytokines IL-4 and IL-5 in the bronchoalveolar lavage fluids and mucosal eosinophils, concomitant with an increase in airway responsiveness. The D10 cell-induced responses were seen in the absence of serum specific IgE. In the presence of Ag, the transferred D10 cells not only remained in the lungs, but also increased in number 72 h post-cell transfer. Although significantly higher levels of IL-4 and IL-5 in the bronchoalveolar lavage fluids were found in D10-transferred mice, the levels of pulmonary eosinophilia, mucus goblet cells, and airway responsiveness were significantly lower than those in Ag-sensitized and -challenged mice. These results demonstrate that although Ag-specific activation of Th2 cells at mucosal sites is able to mediate the recruitment of eosinophils and the subsequent induction of airway hyper-responsiveness, the more severe pulmonary allergic responses were observed only in mice sensitized and challenged with Ag.
CC Chemokine Receptors 1 and 3 Are Differentially Regulated by IL-5 During Maturation of Eosinophilic HL-60 Cells
Authors: Tiffany H. Lee , Alkhatib Ghalib , Combadiere Christophe , Berger Edward A. , Murphy Philip M. 
Published: December 2022

Abstract
CC chemokine receptors 1 and 3 (CCR1 and CCR3) are expressed by eosinophils; however, factors regulating their expression and function have not previously been defined. Here we analyze chemokine receptor expression and function during eosinophil differentiation, using the eosinophilic cell line HL-60 clone 15 as a model system. RNA for CCR1, -3, -4, and -5 was not detectable in the parental cells, and the cells did not specifically bind CC chemokines. Cells treated with butyric acid acquired eosinophil characteristics; expressed mRNA for CCR1 and CCR3, but not for CCR4 or CCR5; acquired specific binding sites for macrophage-inflammatory protein-1α and eotaxin (the selective ligands for CCR1 and CCR3, respectively); and exhibited specific calcium flux and chemotaxis responses to macrophage-inflammatory protein-1α, eotaxin, and other known CCR1 and CCR3 agonists. CCR3 was expressed later and at lower levels than CCR1 and could be further induced by IL-5, whereas IL-5 had little or no effect on CCR1 expression. Consistent with the HIV-1 coreceptor activity of CCR3, HL-60 clone 15 cells induced with butyric acid and IL-5 fused with HeLa cells expressing CCR3-tropic HIV-1 envelope glycoproteins, and fusion was blocked specifically by eotaxin or an anti-CCR3 mAb. These data suggest that CCR1 and CCR3 are markers of late eosinophil differentiation that are differentially regulated by IL-5 in this model.
Subcongenic Analysis of theIdd13Locus in NOD/Lt Mice: Evidence for Several Susceptibility Genes Including a Possible Diabetogenic Role for β2-Microglobulin
Authors: Serreze David V. , Bridgett Margot , Chapman Harold D. , Chen Emmie , Richard Scott D. , Leiter Edward H. 
Published: December 2022

AbstractAlthough they share ∼88% of their genome with NOD mice including the H2g7 haplotype, NOR mice remain free of T cell-mediated autoimmune diabetes (IDDM), due to non-MHC genes of C57BLKS/J (BKS) origin. NOR IDDM resistance was previously found to be largely controlled by the Idd13 locus within an ∼24 cM segment on Chromosome 2 encompassing BKS-derived alleles for H3a, B2m, Il1, and Pcna. NOD stocks carrying subcongenic intervals of NOR Chromosome 2 were utilized to more finely map and determine possible functions of Idd13. NOR- derived H3a-Il1 (∼6.0 cM) and Il1-Pcna (∼1.2 cM) intervals both contribute components of IDDM resistance. Hence, the Idd13 locus is more complex than originally thought, since it consists of at least two genes. B2m variants within the H3a-Il1 interval may represent one of these. Monoclonal Ab binding demonstrated that dimerizing with the β2ma (NOD type) vs β2mb isoform (NOR type) alters the structural conformation, but not total expression levels of H2g7 class I molecules (e.g. Kd, Db). β2m-induced alterations in H2g7 class I conformation may partially explain findings from bone marrow chimera analyses that Idd13 modulates IDDM development at the level of non-hematopoietically derived cell types controlling selection of diabetogenic T cells and/or pancreatic β cells targeted by these effectors. Since trans-interactions between relatively common and functionally normal allelic variants may contribute to IDDM in NOD mice, the search for Idd genes in humans should not be limited to functionally defective variants.