bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine messenger RNA expression for IL-3, IL-4, IL-5, and granulocyte/macrophage-colony-stimulating factor in the nasal mucosa after local allergen provocation: relationship to tissue eosinophilia.
Authors: Durham S R , Ying S , Varney V A , Jacobson M R , Sudderick R M , Mackay I S , Kay A B , Hamid Q A 
Published: December 2022

Abstract
Tissue eosinophilia is characteristic of human atopic allergic inflammation, although the mechanism is largely unknown. In this study we test the hypothesis that eosinophil infiltration during allergen-provoked rhinitis in hayfever sufferers may occur as a consequence of activation of a population of cells having a characteristic cytokine profile equivalent to the murine Th lymphocyte Th2 subset. Biopsies of the nasal inferior turbinate were obtained from 10 grass pollen-sensitive patients 24 h after local nasal provocation with allergen and after a control challenge with the allergen diluent. Biopsies were divided into two and subsequently processed for in situ hybridization using 35S-labeled RNA probes for selected cytokines and for immunohistology using an eosinophil granule mAb (EG2) which recognizes secreting eosinophils. At allergen-challenged sites compared with control sites there were significant increases in mRNA+ cells for IL-3 (p less than 0.04), IL-4 (p = 0.01), IL-5 (p = 0.02) and granulocyte/macrophage-CSF (p = 0.03). In contrast, only occasional hybridization signals were observed for IL-2 and IFN-gamma at both allergen and control sites. After allergen there was an increase (p = 0.01) in EG2+ eosinophils and significant correlations were observed between EG2+ cells and mRNA expression for "Th2-type" cytokines, particularly IL-5 (r = 0.90, p less than 0.0001). These results demonstrate that recruitment of eosinophils during human allergen-induced rhinitis is associated with cells expressing mRNA for IL-3, IL-4, IL-5, and granulocyte/macrophage-CSF.
E-selectin (endothelial-leukocyte adhesion molecule-1) is not required for the migration of neutrophils across IL-1-stimulated endothelium in vitro.
Authors: Furie M B , Burns M J , Tancinco M C , Benjamin C D , Lobb R R 
Published: December 2022

Abstract
Treatment of vascular endothelial cells with inflammatory cytokines stimulates surface expression of E-selectin (previously known as endothelial-leukocyte adhesion molecule-1) and promotes the transendothelial migration of neutrophils. To assess participation of E-selectin in cytokine-mediated neutrophil migration, an in vitro model consisting of monolayers of human umbilical vein endothelial cells (HUVEC) grown on amniotic connective tissue was used. When HUVEC-amnion cultures were stimulated for 4 h with relatively low concentrations of IL-1 (0.1 to 0.15 U/ml), mAb BB11 or H18/7 to E-selectin partially inhibited migration of subsequently added neutrophils. However, when the cultures were stimulated with 15 U/ml of IL-1 for 4 or 24 h, little to no inhibition was observed. mAb to E-selectin also failed to inhibit migration of neutrophils across HUVEC-amnion cultures treated with low doses of IL-1 when the leukocytes were additionally stimulated by the chemoattractant leukotriene B4. In contrast, migration of neutrophils across IL-1-treated HUVEC was profoundly inhibited by mAb to CD11/CD18 leukocytic integrins under all conditions tested. Results of these studies suggest that participation of E-selectin is not essential for migration of neutrophils across cytokine-stimulated HUVEC in vitro; rather, E-selectin can be bypassed in favor of CD11/CD18-dependent mechanisms under appropriate circumstances.
In vivo binding and clearance of circulating antigen by bispecific heteropolymer-mediated binding to primate erythrocyte complement receptor.
Authors: Taylor R P , Reist C J , Sutherland W M , Otto A , Labuguen R H , Wright E L 
Published: December 2022

Abstract
We have used the avidin/biotin system to construct soluble, cross-linked bispecific heteropolymers containing mAb to both the primate E C receptor and the DNP group. These heteropolymers facilitate in vitro binding of DNP-bovine gamma-globulin (DNP-BGG) to both human and squirrel monkey E. Intravenous injection in squirrel monkeys of DNP-BGG followed by heteropolymer leads to E binding and clearance from the circulation of a significant fraction of both heteropolymer and DNP-BGG, without lysis or clearance of the E. This methodology may potentially be used to treat a variety of infectious diseases and other syndromes associated with blood-borne pathogens.
Critical role of corneal Langerhans cells in the CD4- but not CD8-mediated immunopathology in herpes simplex virus-1-infected mouse corneas.
Authors: Hendricks R L , Janowicz M , Tumpey T M 
Published: December 2022

Abstract
Previous studies have revealed that the RE strain of HSV type 1 (HSV-1) induces a tissue-destructive inflammatory response in the mouse cornea that is mediated by CD4 T lymphocytes, whereas the KOS strain of HSV-1 preferentially activates CD8 T lymphocytes in the cornea. Langerhans cells (LC) normally reside only at the periphery of the cornea but can migrate centripetally after HSV-1 infection. We studied the relative contribution of LC to the corneal inflammation induced by the KOS and RE strains of HSV-1. Ten days after infection, the central one-third of RE HSV-1-infected corneas contained an average of 5.7 LC/high-power field compared with 0.6 LC/high-power field in KOS-infected corneas. We hypothesized that the increased density of LC in RE HSV-1-infected corneas at the time of T lymphocyte infiltration contributed to the preferential activation of CD4 T lymphocytes in these corneas. To test this hypothesis, we gave mice a low dose of UV-B corneal irradiation (150 mJ/cm2) 1 day before infection with HSV-1. UV-B irradiation effectively prevented the migration of LC into the central cornea when measured 10 or 21 days after corneal infection with either HSV-1 strain. UV-B corneal irradiation had no effect on the CTL response to HSV-1 Ag in the regional lymph nodes after corneal infection with KOS or RE HSV-1. The delayed-type hypersensitivity response induced by both strains of virus, when measured 8 and 14 days after corneal infection, was significantly reduced by UV-B irradiation. UV-B irradiation significantly reduced the incidence (p = 0.0023) and severity (p = 0.0008) of corneal stromal disease induced by RE HSV-1 but did not significantly affect the stromal disease induced by KOS HSV-1. To distinguish between the effect of UV-B treatment on the afferent and efferent arms of the Ir in mice, we administered UV-B treatment to one eye, followed 24 h later by RE HSV-1 infection of both eyes. These mice developed a normal delayed-type hypersensitivity response, and stromal inflammation developed normally in the untreated eye. However, stromal inflammation was significantly reduced in the treated eye. Our findings suggest that LC play a critical role in the activation of HSV-reactive CD4 T lymphocytes in the cornea. Moreover, the type of corneal inflammation induced by different strains of HSV-1 may reflect their differential capacity to induce LC migration into the central cornea.
Imaging early steps of human T cell activation by antigen-presenting cells.
Authors: Donnadieu E , Cefai D , Tan Y P , Paresys G , Bismuth G , Trautmann A 
Published: December 2022

Abstract
In this work the Ca2+ response and the morphological changes elicited by Ag in human CD4+ T cells are described at the single cell level. The APC used to present the diphtheria toxoid Ag to a human diphtheria toxoid-specific T cell clone were murine L cell fibroblast transfectants expressing MHC class II molecules. The increase of the intracellular Ca2+ concentration, [Ca2+]i, which is one of the earliest steps of the response to TCR stimulation, was followed by fluorimetry with fura-2 on an imaging system. This response was a specific consequence of successful Ag presentation, because it only took place when fibroblasts expressed both class II MHC molecules and Ag. CD4 molecules were also involved in this intercellular interaction, because the Ca2+ response could be inhibited by preincubating the T cells with an anti-CD4 antibody. The response induced by APC started after a delay of at least 6 min, after which large Ca2+ oscillations took place, with a pseudo period of 100 s at 35 degrees C. The frequency of these oscillations decreased with temperature. The oscillations became progressively more damped during the first 30 to 40 min of cell-to-cell interaction, after which they completely stopped; however, [Ca2+]i remained well above its resting level for more than 1 h after the contact. The Ca2+ oscillations were entirely dependent on Ca2+ influx because they immediately disappeared when external calcium was removed. Similar oscillations were observed when the cells were stimulated with an anti-CD3 antibody. After stimulation with APC, many T cells abandoned their spherical shape and tended to flatten and elongate. This aspect of the T cell response was not observed after stimulation with an anti-CD3 antibody. In the presence of cytochalasin B, the morphologic changes elicited by the APC were blocked, whereas the Ca2+ response was slightly enhanced. However, when T cells were loaded with the Ca2+ chelator BAPTA, both Ca2+ and morphologic changes were inhibited, suggesting that the Ca2+ response plays a permissive role for the morphologic changes.
Control of allergic reactivity in human filariasis. Predominant localization of blocking antibody to the IgG4 subclass.
Authors: Hussain R , Poindexter R W , Ottesen E A 
Published: December 2022

Abstract
Patients with chronic helminth infections, despite having abundant basophils and mast cells specifically sensitized with antiparasite IgE and often exposed repeatedly to parasite Ag, rarely manifest allergic symptoms. This control of clinical allergic reactivity likely results from Ag-specific IgG "blocking antibodies" shown previously to be abundant in the sera of such patients. In the present study we used two approaches to determine in which of the four IgG subclasses this blocking activity was localized. First, specific antifilarial antibodies of each of the four IgG subclasses were quantified in the sera of 28 patients with Bancroftian filariasis and correlated with the levels of blocking activity in these sera (determined by histamine release assays). A significant correlation with blocking activity was seen only for antibodies of the IgG4 subclass, and, indeed, the correlation was especially strong in the group of totally asymptomatic patients (but with microfilariae circulating in the blood) in whom blocking antibody levels were highest. Interestingly, however, if the analysis excluded these asymptomatic microfilaremic patients and focused instead on those with lymphatic inflammatory pathology (who had relatively low levels of both serum blocking activity and specific IgG4 antibodies), then the small amount of blocking activity found in these sera correlated only with the levels of IgG1 subclass antibodies. The second approach utilized selective depletion of IgG4 (by anti-IgG4 affinity columns) from the sera of three microfilaremic patients with high levels of blocking activity and demonstrated clearly that removal of IgG4 abolished the majority of the blocking activity in these sera (53, 78, and 81%). These two sets of findings demonstrate a predominant role for specific IgG4 antibodies in blocking IgE-mediated allergic responses to the parasite Ag in vitro, but they also indicate that in some situations IgG1 antibodies can block such reactions. Furthermore, the correlation demonstrated between patients' clinical presentations and the levels of both their specific IgG4 antibodies and serum blocking activity suggests that these antibodies play a similar role in vivo as well.
IFN-gamma mediates increased glucocorticoid receptor expression in murine macrophages.
Authors: Salkowski C A , Vogel S N 
Published: December 2022

Abstract
Exposure of the murine macrophage cell line, RAW 264.7, to murine rIFN-gamma resulted in a significant increase in the number of glucocorticoid receptors (GcR). A doubling in the number of GcR was observed as early as 24 h after rIFN-gamma treatment, and receptor number was maximal by 36 h after rIFN-gamma treatment and represented approximately a fourfold increase. Scatchard analysis indicated that a twofold increase in GcR affinity was concomitant with the rIFN-gamma-induced increase in GcR number in RAW 264.7 cells. Increased GcR numbers were induced after exposure of RAW 264.7 cells to as little as 0.1 U/ml rIFN-gamma, and optimal expression was observed at 5 U/ml. Treatment of peritoneal exudate macrophages from C3H/OuJ mice and the LPS hyporesponsive mouse strain, C3H/HeJ, with rIFN-gamma induced an approximately twofold increase in the GcR with no concomitant change in receptor affinity. These results suggest that IFN-gamma may be essential not only for macrophage activation, but also for increasing macrophage sensitivity to feedback inhibition by glucocorticoids by increasing the number and/or affinity of available GcR.
Effects of eleven cytokines and of IL-1 and tumor necrosis factor inhibitors in a human B cell assay.
Authors: Tucci A , James H , Chicheportiche R , Bonnefoy J Y , Dayer J M , Zubler R H 
Published: December 2022

Abstract
The effects of different recombinant human cytokines and cytokine inhibitors were compared in a culture system in which cell contact with mutant EL-4 thymoma cells of murine origin efficiently stimulates human B cell proliferation and Ig secretion in conjunction with human T cell supernatant. IL-1 alpha, IL-1 beta, TNF-alpha, and IL-2 co-stimulated B cell proliferation and IgM, IgG, and IgA secretion, whereas IL-3, IL-4, IL-5, IL-6, IFN-gamma, or GM-CSF had weak or no activity in this regard. In contrast, TGF-beta 1 was strongly inhibitory. A very strict hierarchy of cytokine interactions was found in that IL-1 was necessary to induce TNF-alpha responsiveness, and TNF-alpha the IL-2 responsiveness, of the B cells. Most likely the small number of starting B cells in the present assay (300 FACS-separated B cells/200 microliters) minimized the effects of autocrine B cell factors. IL-4 together with IL-1 induced IgE secretion, and the IgE secretion was further increased by TNF-alpha. IFN-gamma had no modulatory effect on the IL-4 dependent IgE response in this system. Pretreatment of B cells with IL-1R antagonist (IL-1ra, which binds to IL-1R) or addition of soluble TNF receptor type 1 (sTNF-R55, which binds to TNF) completely inhibited the IL-1 or TNF-alpha effects, respectively. This occurred in a specific manner; the inhibition was reversed by a large excess of cytokine. IL-1ra also inhibited a B cell response induced by PMA-preactivated EL-4 cells alone. Because B cells responding to such preactivated EL-4 cells did not acquire TNF-alpha responsiveness, no IL-1 was apparently involved under this assay condition. It appears, therefore, 1) that IL-1ra can act on B cells and 2) that this antagonist may not only block IL-1R, but may provide a direct or indirect inhibitory signal interfering even with IL-1-independent B cell activation.
A member of the tetra spans transmembrane protein superfamily is recognized by a monoclonal antibody raised against an HLA class I-deficient, lymphokine-activated killer-susceptible, B lymphocyte line. Cloning and preliminary functional studies.
Authors: Gil M L , Vita N , Lebel-Binay S , Miloux B , Chalon P , Kaghad M , Marchiol-Fournigault C , Conjeaud H , Caput D , Ferrara P 
Published: December 2022

Abstract
The IA4 mAb was identified among a series of antibodies raised in BALB/c mice after immunization against a HLA class I-deficient, lymphokine-activated killer (LAK)-susceptible EBV-B lymphocyte line. The IA4 antibody was selected because of its high expression, in the range of 10(5) to 25 x 10(5) sites/cell, on several B lymphocyte lines (EBV-transformed or Burkitt) and monocytic lines such as HL60 and U937, and because its expression was correlated with both target susceptibility to LAK lysis and reduced expression of HLA class I surface Ag on two pairs of EBV-B-transformed cell lines (721/721.134 and MM/10F2). Despite the strategy followed to raise the mAb and the correlation mentioned above, no direct role of the IA4 molecules in LAK susceptibility has been established, since the IA4 molecule is poorly expressed on the sensitive targets Daudi and K562; moreover, the IA4 antibody did not affect reproducibly the in vitro killing of positive target cells by LAK effectors. The IA4 antibody was poorly immunoprecipitating and the surface molecule recognized was identified by gene cloning following an expression strategy using a U937 cDNA library transfected in COS cells, and a screening strategy based on membrane expression of IA4 molecule. The IA4 cDNA is virtually identical to "R2," a mRNA species previously identified in activated human T cells by subtractive hybridization. The IA4 cDNA contains an open reading frame coding for a protein 267 amino acids long with four potential transmembrane domains and one large external hydrophilic domain of about 110 amino acids, possibly glycosylated. The encoded protein belongs to a family of surface molecules, the tetra spans transmembrane protein superfamily, all displaying the four transmembrane domains, expressed on various cell types including lymphocytes (CD9, CD37, CD53, TAPA-1), melanoma cells (ME491), and intestinal cells (CO-029). These molecules have been reported to be involved in cell activation and cell death. Surprisingly, the Schistosoma mansoni Ag Sm23 displays significant homologies with this family. The IA4 molecule is a widely distributed surface marker expressed on circulating lymphocytes and monocytes, newborn thymocytes, and the cell lines mentioned above. The IA4 molecule expression is up-regulated upon cell activation. Weakly expressed on resting peripheral T and B lymphocytes and large granular lymphocytes (NK), its expression roughly doubles after activation by PHA, staphylococcus aureus Cowan I, and IL-2, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
Appearance of T lymphocyte-derived proteins specific for the immunizing antigen in serum during a humoral immune response.
Authors: Urbanski M , Cone R E 
Published: December 2022

Abstract
Some T lymphocytes produce extracellular proteins that bind nominal antigen specifically (TABM), and these proteins exhibit potent immunoregulatory activity. We have utilized an ELISA for Ag binding by Ag-specific TABM to detect and quantitate the appearance of Ag-specific TABM in murine serum during a humoral Ir to protein Ag. The TABM response was specific for the inducing Ag, stronger and more rapid during a secondary response, and temporally distinct from the appearance of Ig. The non-Ig serum TABM were bound by mAb specific for TCR-alpha chains and isolated by affinity for Ag were Mr 110,000 polypeptides. The TABM response did not occur in scid/scid mice unless the mice were reconstituted with thymocytes and thymocyte-reconstituted scid/scid mice produced TABM, but did not produce Ig. The results suggest that soluble TABM are an Ag-specific humoral manifestation of the Ir of some T lymphocytes.
Effect of H chain V region on complement activation by immobilized immune complexes.
Authors: Horgan C , Brown K , Pincus S H 
Published: December 2022

Abstract
Activation of C by immune complexes (IC) in tissues and the inflammatory consequences are major determinants in the pathogenesis of many autoimmune disorders. To assess the factors involved in C activation by such IC, we examined the binding of C components by chimeric IgG1 antibodies bound to immobilized Ag. We previously reported that alterations in the H chain V regions can affect the binding of first component of C (C1q) and a major breakdown product of the third C component (C3b) when otherwise identical antibodies were bound to immobilized (Tyr, Glu)-Ala-Lys. To evaluate C activation of these antibodies in well defined IC, we utilized a 9-amino acid peptide conjugated to BSA as Ag. The peptide:BSA conjugate was bound similarly by the two IgG1 antibodies which differed mainly in the CDR3 regions, but also in 9 other amino acids in the H chain V region. When soluble IC were prepared with the two antibodies, they activated C similarly. However, C activation by solid phase Ag:antibody complexes differed; we found that antibody 10B bound more C1q and C3b than antibody B11 did, unless the Ag was present at high density on the plates. These data suggest that the variable region differences affect C activation by these antibody when they are bound to immobilized Ag. Furthermore, these results underscore the differences in C activation by the same antibody depending upon whether the IC are free in solution or immobilized.
Substituted isocoumarins as inhibitors of complement serine proteases.
Authors: Kam C M , Oglesby T J , Pangburn M K , Volanakis J E , Powers J C 
Published: December 2022

Abstract
Inhibition of complement proteins D, B, C2, C1s, C1r, I, and the catalytic fragments Bb and C2a by substituted isocoumarins was investigated. 3,4-Dichloroisocoumarin, a general serine protease inhibitor, inhibited factor D, C1r, and C1s moderately with second-order inhibition constants (kobs/[I]) of 40 to 190 M-1 s-1, but it did not inhibit C2, factor B, C2a, or Bb. The best inhibitor for factors D and B was 4-chloro-7-guanidino-3-methoxyisocoumarin with kobs/[I] values of 250 and 290 M-1 s-1, respectively. Most isocoumarins did not inhibit C2 or C2a; only 4-chloro-3-isothiureidoalkoxyisocoumarins were slightly inhibitory. 3-Alkoxy-4-chloro-7-guanidinoisocoumarins inhibited C1r and C1s moderately. The best inhibitor for C1r and C1s was 4-chloro-3-(3-isothiureidopropoxy)isocoumarin with kobs/[I] values of 6,600 and 130,000 M-1 s-1, respectively. Fifty amino acid or peptide thioesters containing Arg or other amino acids at the P1 site were tested as substrates of factor I, however none was hydrolyzed. Isocoumarins substituted with chloro and basic groups such as guanidino and isothiureidoalkoxy inhibited factor I activity with its natural substrate C3b, but kobs/[I] values were low. 4-Chloro-3-ethoxy-7-guanidinoisocoumarin inhibited activation of the alternative pathway and, to a lesser extent, of the classical pathway in serum. Several other substituted isocoumarins also inhibited cobra venom factor-initiated activation of the alternative pathway in serum.
Primary listerial infections are exacerbated in mice administered neutralizing antibody to macrophage colony-stimulating factor.
Authors: Gregory S H , Wing E J , Tweardy D J , Shadduck R K , Lin H S 
Published: December 2022

Abstract
The serum and tissue levels of macrophage colony-stimulating factor (M-CSF) are elevated in mice during a primary immunologic response to infection by Listeria monocytogenes. Experiments were performed to determine the specific role of M-CSF in the resolution of listerial infections. The bulk of Listeria injected into a mouse i.v. is deposited in the liver. The expression of M-CSF mRNA in the liver increased markedly within 2 h postinfection. Maximum expression was dependent upon the dose of Listeria inoculated. The administration of anti-M-CSF mAb reduced the percentage of Mac-1+ mononuclear phagocytes subsequently found in the livers of infected animals. This reduction correlated inversely with an increase in the number of Listeria associated with both the parenchymal and NPC populations. These results suggest that M-CSF may play an important role in the primary immunologic response to Listeria in the liver by stimulating the production, mobilization, and/or biologic activity of Mac-1+ mononuclear phagocytes.