bluuebunny/crossref_metadata_2025_split huggingface dataset:
Filarial-specific IgG4 response correlates with active Wuchereria bancrofti infection.
Authors: Kwan-Lim G E , Forsyth K P , Maizels R M 
Published: December 2022

Abstract
The filarial-specific humoral immune response of adult residents of two areas of Papua New Guinea, differing in transmission of Wuchereria bancrofti infection was compared. The majority of residents of the village of Bonahoi, in an area where transmission of filariasis had been interrupted by a 20-year insecticide spray program to control malaria, showed no parasitologic signs of active W. bancrofti infection and were negative for both circulating phosphorylcholine Ag and peripheral blood microfilariae. In contrast, adult residents of the village of Nanaha were in an area exposed to infection, and were phosphorylcholine-Ag- and microfilariae-positive. The antibody response of these two groups to both adult worm excretory/secretory (ES) Ag and somatic antigen extract was examined to determine which components of the filarial-specific immune response were dependent on active infection. Identification of these immune responses may point to immunologic methods to evaluate control programs for lymphatic filariasis. Adults from Bonahoi were found to have significant immune responses to [35S] methionine-labeled ES Ag by immunoprecipitation and to adult somatic antigen extracts by ELISA and by immunoblotting. This result is consistent with the fact that these individuals were previously exposed to and/or infected with W. bancrofti. Similarly, residents of the endemic village had detectable immune responses to these Ag irrespective of if they were microfilaremic. The most striking immunologic difference observed between the two groups was that residents of Bonahoi had a dramatically reduced filarial-specific IgG4 antibody response to both adult somatic Ag and adult ES Ag. These data suggest that longitudinal measurement of filarial-specific IgG4 levels may be a useful seroepidemiologic indicator of changes in W. bancrofti infection status.
Glucocorticoid-regulated gene expression in the immune system. Analysis of glucocorticoid-regulated transcripts from the mouse macrophage-like cell line P388D1.
Authors: Helmberg A , Fässler R , Geley S , Jöhrer K , Kroemer G , Böck G , Kofler R 
Published: December 2022

Abstract
To further elucidate the molecular mechanisms underlying glucocorticoid-mediated immune suppression, we have exploited cDNA cloning and subtractive screening methods to identify glucocorticoid-regulated transcripts in the mouse macrophage-like cell line, P388D1. Two of the three isolated glucocorticoid-regulated mRNA species corresponded to genes potentially important to immunoregulation: one glucocorticoid-suppressed mRNA species probably encoded the previously uncloned 3-hydroxy-3-methylglutaryl coenzyme A reductase, an enzyme that appears important for in vitro immune responses. The other mRNA species showed glucocorticoid-increased mRNA steady-state levels and was transcribed from an endogenous ecotropic type C retroviral locus. This transcript gives rise to a protein (transmembrane retroviral protein, formerly p15E), which, along with its feline and human homologs, has been implicated in immunosuppression caused by mouse, cat, and human retroviruses. Our results raise the possibility that the immunosuppressive activity of glucocorticoids might be mediated, in part, by regulating the expression of the above immunoregulatory proteins.
A murine very late activation antigen-like extracellular matrix receptor involved in CD2- and lymphocyte function-associated antigen-1-independent killer-target cell interaction.
Authors: Takahashi K , Nakamura T , Koyanagi M , Kato K , Hashimoto Y , Yagita H , Okumura K 
Published: December 2022

Abstract
CD2 and lymphocyte function-associated antigen (LFA)-1 are well known as T cell adhesion molecules involved in killer-target cell interactions. However, our recent study revealed that molecule(s) other than CD2 and LFA-1 might be involved in the lymphokine-activated killer (LAK) cell cytotoxicity against certain target cells. In order to characterize such unknown molecules, we established a mAb (RMV-7) which could inhibit CD2/LFA-1-independent LAK cell cytotoxicity and binding to target cells at the effector site. The Ag identified by RMV-7 appeared on splenic T cells late after mitogenic stimulation and was a noncovalently linked heterodimer composed of a 140-kDa alpha-chain and a 95-kDa beta-chain. RMV-7 blocked LAK cell binding to fibronectin (FN), fibrinogen, and vitronectin but not that to laminin or type IV collagen, indicating that the RMV-7-defined molecule is a unique extracellular matrix receptor for FN, fibrinogen, and vitronectin. One of its ligand, FN, was found on the surface of several target cells, and LAK cell cytotoxicity against them was blocked by anti-FN antibody at the target site. Similarly, cytotoxicity of a H-2d-specific CTL clone was inhibited by RMV-7 and anti-FN antibody as well. These results indicate that a unique very late activation Ag-like extracellular matrix receptor on murine CTL and LAK cells contributes to target cell binding and cytotoxicity.
Alloantigen-specific cytotoxic clones bearing the alpha,beta T cell antigen receptor but not CD4 or CD8 molecules.
Authors: Rivas A , Koide J , Laus R , Engleman E G 
Published: December 2022

Abstract
The vast majority of circulating lymphocytes that express the alpha,beta TCR in association with CD3 also express either CD4 or CD8 molecules, which are thought to act as important accessory structures in HLA class II- and I-restricted T cell functions, respectively. In the current study alpha,beta TCR+ clones devoid of detectable CD4 or CD8 were generated by repeated stimulation of fresh CD3+,CD4-,CD8- cells with an allogeneic lymphoblastoid cell line in the presence of conditioned medium containing IL-2. Except for the absence of CD4 and CD8, which was associated with undetectable levels of CD4 and CD8 mRNA, the clones were phenotypically indistinguishable from classical CD3+,alpha,beta TCR+ cells. Furthermore, they mediated potent cytolysis of their specific stimulator line but did not kill irrelevant LCL or NK-sensitive targets. mAb to CD3 and the alpha,beta TCR inhibited cytolysis, suggesting that the clones use the TCR/CD3 complex to recognize and respond to their targets. mAbs to CD2 and CD11a also inhibited cytolysis, indicating that the clones use these accessory molecules to interact with their targets. Finally, cytolysis was inhibited by an HLA-A,B,C framework-specific mAb (W6/32) as well as a mAb (MA2.1) specific for an HLA-A2 epitope. These results demonstrate that CD3+,alpha,beta TCR+,CD4-,CD8- cytotoxic clones can be generated from the peripheral blood of healthy adults, and use their TCR/CD3 complexes to function in an HLA class I-restricted manner.
Granulocyte-macrophage colony-stimulating factor and other cytokines regulate surface expression of the leukocyte adhesion molecule-1 on human neutrophils, monocytes, and their precursors.
Authors: Griffin J D , Spertini O , Ernst T J , Belvin M P , Levine H B , Kanakura Y , Tedder T F 
Published: December 2022

Abstract
There is increasing evidence that cytokines such as granulocyte-macrophage (GM)-CSF can profoundly affect the adhesion, aggregation, and mobility of neutrophils both in vitro and in vivo. However, the mechanisms whereby these factors might alter the adhesive properties of neutrophils are incompletely understood. A new family of cellular adhesion molecules has recently been identified by cDNA cloning. The members of this family include human leukocyte adhesion molecule-1 (LAM-1), the human endothelial-leukocyte adhesion molecule, and the mouse leukocyte homing receptor for high endothelial venules, MEL-14. LAM-1 is the human homologue of murine MEL-14, and is believed to mediate binding of leukocytes to human high endothelial venules. LAM-1 can be identified by mAb TQ-1, Leu 8, or anti-LAM1.1. The expression and regulation of LAM-1 on granulocytes, monocytes, and their precursors was investigated using flow cytometry and the anti-LAM-1.1 mAb. Neutrophils, eosinophils, monocytes, marrow myeloid cells, granulocyte/macrophage colony-forming unit, and burst-forming unit for erythroid cells were LAM-1+ by flow microfluorimetry. The regulation of LAM-1 expression was tested by treating various cell populations with cytokines or other stimuli for 0-90 min. Exposure of neutrophils, monocytes, and marrow myeloid cells to GM-CSF induced rapid and complete loss of LAM-1 from the cell surface, but had no effect on LAM-1 expression by lymphocytes. The loss of LAM-1 was temporally correlated with up-regulation of CD11b (Mo1), an adhesion molecule involved in neutrophil aggregation. Several other factors known to activate neutrophils also caused down-regulation of LAM-1 and up-regulation of CD11b, including TNF, FMLP, and leukotriene B4. Interestingly, granulocyte-CSF and IFN-gamma had minimal effects on neutrophil LAM-1 expression. Similar results were observed on monocytes and myeloid precursor cells. Thus, exposure of neutrophils to GM-CSF results in a profound change in surface expression of adhesion molecules, with coordinated up-regulation of CD11b and down-regulation of LAM-1. These changes in adhesion proteins are likely to alter aggregation and mobility of both mature myeloid cells and their precursors in patients receiving certain types of cytokine therapy.
The IL-2 receptor beta-chain (p70). Ligand binding ability of the cDNA-encoding membrane and secreted forms.
Authors: Tsudo M , Karasuyama H , Kitamura F , Tanaka T , Kubo S , Yamamura Y , Tamatani T , Hatakeyama M , Taniguchi T , Miyasaka M 
Published: December 2022

Abstract
The high affinity IL-2R is composed of at least two distinct subunits; alpha (p55 or Tac)- and beta (p70)-chains. Recent cDNA expression studies with lymphoid cells unequivocally demonstrated that the IL-2R beta is an indispensable component for the ligand internalization and the signal transduction via the high affinity IL-2R. Furthermore, these studies confirmed that the IL-2R beta singly expressed on T lymphoid cells represents the intermediate affinity IL-2R. In the present study, however, we show 1) the IL-2R beta expressed on a mouse fibroblast line, NIH-3T3, did not bind IL-2 under the intermediate affinity conditions, 2) nevertheless, the IL-2R beta coexpressed with the IL-2R alpha not only formed the high affinity receptor but also internalized IL-2. By the use of competitive sandwich ELISA to study the IL-2 binding ability of the IL-2R beta molecule itself, we also show that the IL-2R beta present in the detergent-solubilized cell extracts and the secreted IL-2R beta (p37) produced by the truncated cDNA are actually capable of binding IL-2, but with a much reduced affinity compared with the intact IL-2R beta expressed on the lymphoid cells. These findings lead us to postulate a more complex feature of the IL-2R than ever speculated; the IL-2R beta molecule having on its own minimal IL-2 binding ability requires a putative gamma-chain specifically present on lymphoid cells to generate the functional intermediate affinity IL-2R. The gamma-chain, however, seems not to be required as far as the formation of the high affinity IL-2R by the alpha- and beta-chains and the ligand internalization through it are concerned.
Signal transduction initiated by extracellular nucleotides regulates the high affinity ligand recognition of the adhesive receptor CD11b/CD18.
Authors: Altieri D C , Wiltse W L , Edgington T S 
Published: December 2022

Abstract
A variety of monocyte/neutrophil adhesive functions is coordinated by the CD11b/CD18 complex, a leukocyte-restricted member of integrin receptors. Previous studies have shown that the adenine nucleotide ADP produces a transient and high affinity recognition state of CD11b/CD18 for its complementary ligands fibrinogen and factor X. We have now characterized the process of intracellular signalling initiated in monocytes by ADP. Further, we have causally related these events to the qualitative upregulation of CD11b/CD18, as exemplified by its inducible binding of factor X. Micromolar concentrations of ADP or ATP produce dose-dependent increase in monocyte cytosolic free [Ca2+]i through mobilization from intracellular stores coupled with a sustained, EGTA-sensitive, influx of Ca2+ from the external compartment. This Ca2+ response was kinetically and quantitatively heterogeneous when analyzed at the single cell level. Ca2+ channel antagonists nifedipine or verapamil blocked the sustained phase of ADP-induced Ca2+ entry and inhibited 125I-factor X binding to CD11b/CD18 in a dose-dependent manner. Nifedipine-sensitive Ca2+ channels are gated by variations in transmembrane potential in a variety of cells. In monocytes, depolarizing conditions by high external [K+] or by the Na+ ionophore gramicidin D mimicked the stimulatory effect of ADP, inducing increased cytosolic free [Ca2+]i and 125I-factor X binding to CD11b/CD18. In contrast, these responses were both abrogated by hyperpolarization with the K+ ionophore valinomycin. These data suggest that a sustained increase in monocyte cytosolic free [Ca2+]i coupled with variations in transmembrane potential regulate the high affinity receptor function of CD11b/CD18. Although prototypically exemplified for monocyte stimulation with adenine nucleotides, this pathway of intracellular signalling might provide a general mechanism for transient and qualitative functional upregulation of integrin receptors.
Production of hydrogen peroxide by rabbit articular chondrocytes. Enhancement by cytokines.
Authors: Tiku M L , Liesch J B , Robertson F M 
Published: December 2022

Abstract
Recent evidence suggests that reactive oxygen intermediates may play a role in the etiology of cartilage matrix degradation in arthritis. We have previously established that normal articular chondrocytes can functionally act as macrophages. These functions include expression of class II MHC Ag, presentation of Ag and induction of mixed and autologous lymphocyte stimulation. Inasmuch as the production of reactive oxygen intermediates is a hallmark of macrophage activity during inflammatory response, we were interested in examining the ability of normal articular chondrocytes to produce reactive oxygen intermediates. Using the trapped indicator 2',7'-dichlorofluorescin diacetate (DCFH-DA), we measured the levels of intracellular hydrogen peroxide within normal rabbit articular chondrocytes. We found that Concanavalin A induces chondrocytes to rapidly oxidize 2',7'-dichlorofluorescin diacetate to a highly fluorescent dichlorofluorescin in a dose- and time-dependent manner. Fluorescent dichlorofluorescin oxidation by chondrocytes was inhibited by the addition of catalase, an enzyme that detoxifies hydrogen peroxide. Exposure of rabbit chondrocytes to either IFN-gamma or TNF primed the chondrocytes to produce significantly greater amounts of hydrogen peroxide with or without further stimulation. Using scopoletin oxidation as a measure of the release of hydrogen peroxide, we confirmed that chondrocytes released this reactive oxygen intermediate after adherence to serum coated culture plates. Rabbit articular chondrocytes produced and released greater amounts of hydrogen peroxide than pulmonary alveolar macrophages, a well characterized macrophage cell type. These observations suggest that chondrocytes are an important source of reactive oxygen intermediates. Furthermore, the production of reactive oxygen intermediates by chondrocytes may be an important mechanism by which chondrocytes induce structural and functional alterations in cartilage matrix observed during arthritis.
Intraintestinal migration to the epithelium of protective, dividing, anti-Trichinella spiralis CD4+ OX22- cells requires MHC class II compatibility.
Authors: Wang C H , Korenaga M , Sacuto F R , Ahmad A , Bell R G 
Published: December 2022

Abstract
We have measured the intraintestinal migration of activated Th cells belonging to the OX8- OX22- and OX8- OX22+ subsets derived from thoracic duct lymph of rats infected with Trichinella spiralis. Cells in S-phase were labeled with 125I-UdR or 3H-TdR in vitro and transfused i.v. Identical proportions of both helper cell subsets localized in the small intestine but three to four times as many OX22- cells as OX22+ cells migrated to the intestinal epithelium. Experiments using MHC class I and II recombinant rats indicated that localization of OX8- OX22- cells in the lower lamina propria (LP) and muscularis was reduced by 50% in MHC class II incompatible rats as assessed by total gamma-counts but by a factor of three when labeled cells were counted. Movement of labeled OX8- OX22- cells to the epithelium was reduced by a factor of five to seven when assessed by the same methods. Quantitative cellular localization in the gut and further movement to the epithelium were normal in class I-mismatched rats. The movement from the lower-mid LP to the epithelium was undertaken principally by dividing cells as indicated by a progressive loss of grain counts in labeled cells and the appearance of doublet-cells in mitosis. In allogeneic combinations, extravasating cells remained localized close to their primary site of exit in the muscularis and lower-mid LP. The results suggest that the requirement for MHC class II compatibility for adoptive transfer of immunity in rats to T. spiralis is functionally related to localization of the protective OX22- cell subset in the epithelium.
Regulation of tumor necrosis factor gene expression and protein synthesis in murine macrophages treated with recombinant tumor necrosis factor.
Authors: Descoteaux A , Matlashewski G 
Published: December 2022

Abstract
The effect of murine rTNF-alpha on c-fos and TNF mRNA accumulation and protein synthesis was investigated in bone marrow-derived macrophages to examine the mechanism(s) by which TNF modulates macrophage activity. A rapid and transient expression of the c-fos gene was induced by murine rTNF. This was blocked by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, suggesting that the murine rTNF stimulated a protein kinase C-dependent signal transduction pathway. Although LPS induced the accumulation of one TNF mRNA species, murine rTNF induced the synthesis of two distinct TNF mRNA species. Both LPS- and murine rTNF-induced TNF mRNA accumulation was equally enhanced by pretreatment with mouse rIFN-gamma. In contrast, cycloheximide pretreatment had little effect on murine rTNF-induced TNF mRNA accumulation, whereas this treatment increased LPS-induced TNF mRNA by sevenfold. These results argue that TNF mRNA accumulation can be modulated in macrophages by distinct mechanisms. As assessed by Western blot and immunoprecipitation analysis, LPS stimulated the synthesis of both cell-associated and secreted forms of TNF protein. In comparison, newly synthesized TNF protein was not detected when macrophages were treated with murine rTNF alone or in combination with murine rIFN-gamma. This demonstrates that although murine rTNF stimulated the synthesis of two distinct TNF mRNA species, additional signal(s) are necessary for their translation into protein and that such signals are present after LPS stimulation.
Association of Ig L chain-like protein lambda 5 with a 16-kilodalton protein in mouse pre-B cell lines is not dependent on the presence of Ig H chain protein.
Authors: Misener V , Jongstra-Bilen J , Young A J , Atkinson M J , Wu G E , Jongstra J 
Published: December 2022

Abstract
Using a polyclonal rabbit antiserum against recombinant mouse lambda 5 protein, we determined that the pre-B cell specific mouse lambda 5 gene encodes a 22-kDa protein. The lambda 5 protein, which is related to conventional Ig lambda L chain proteins forms a complex with Ig mu H chain protein and an as yet unidentified 16-kDa protein (p16) in mu+ pre-B cell lines carrying a functionally rearranged VH-DH-JH allele. In pre-B cell lines which carry DH-JH rearrangements and do not express mu H chain protein, lambda 5 protein is associated with p16. Thus the expression of lambda 5 protein precedes the expression of intact mu H chain protein. This suggests the existence of developmentally regulated protein complexes involving the Ig L chain-like protein lambda 5 and p16 in mu- pre-B cells; lambda 5, p16, and Ig H chain protein in mu+ pre-B cells and Ig H chain and conventional Ig L chain proteins in B cells and plasma cells.
Effect of long-term treatment with platelet-activating factor on IL-1 and IL-2 production by rat spleen cells.
Authors: Pignol B , Hénane S , Sorlin B , Rola-Pleszczynski M , Mencia-Huerta J M , Braquet P 
Published: December 2022

Abstract
To study the effect of the in vivo administration of platelet-activating factor (PAF) on cytokine production, alzet minipumps loaded with the mediator or solvent alone were connected to the jugular vein and placed under the skin of Sprague-Dawley rats. Over 7 days the animals received total doses of 0.5, 1, 4.5, 9, or 28 micrograms PAF or the solvent alone. The spleen mononuclear cells isolated from Ficoll gradients and the adherent cell fraction were separated before determination of basal and mitogen-stimulated IL-1 and IL-2 production, respectively. Adherent splenocytes from rats having received 28 micrograms PAF exhibited a decreased capability to produce IL-1, as compared to those from vehicle-treated animals. In contrast, adherent splenocytes from rats having received 9 and 4.5 micrograms PAF yielded higher amounts of released and cell-associated IL-1 activity upon LPS stimulation, as compared to those from solvent-treated animals. The PAF antagonist, BN 52021, given orally (5 mg/kg, twice a day throughout the experiments) inhibited the in vivo effect of 28 micrograms PAF. Statistically significant 144 +/- 43% (p less than 0.001, n = 5) and 73 +/- 33%, (p less than 0.01, n = 3) increases in IL-2 production were observed when whole spleen mononuclear cells from rats administered with 1 and 4.5 micrograms PAF, respectively, were stimulated with Con A. BN 52021 markedly inhibited the in vivo effect of 1 microgram PAF on the IL-2 release. Our study demonstrates that PAF can modulate immune functions in vivo and suggests that the specific PAF antagonist, BN 52021, may be used as an immunomodulatory agent.