bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-10 inhibits human T cell proliferation and IL-2 production.
Authors: Taga K , Tosato G 
Published: December 2022

Abstract
Human IL-10 has been reported previously to inhibit the secretion of IFN-gamma in PBMC. In this study, we have found that human IL-10 inhibits T cell proliferation to either mitogen or anti-CD3 mAb in the presence of accessory cells. Inhibited T cell growth by IL-10 was associated with reduced production of IFN-gamma and IL-2. Studies of T cell subset inhibition by human IL-10 showed that CD4+, CD8+, CD45RA high, and CD45RA low cells are all growth inhibited to a similar degree. Dose response experiments demonstrated that IL-10 inhibits secretion of IFN-gamma more readily than T cell proliferation to mitogen. In addition, IL-2 and IL-4 added exogenously to IL-10 suppressed T cell cultures reversed completely the inhibition of T cell proliferation, but had little or no effect on inhibition of IFN-gamma production. Thus, in addition to its previously reported biologic properties, IL-10 inhibits human T cell proliferation and IL-2 production in response to mitogen. Inhibition of IFN-gamma production by IL-10 appears to be independent of the cytokine effect of IL-2 production.
Stimulus-response coupling in monocytes infected with Leishmania. Attenuation of calcium transients is related to defective agonist-induced accumulation of inositol phosphates.
Authors: Olivier M , Baimbridge K G , Reiner N E 
Published: December 2022

Abstract
Mononuclear phagocytes infected with Leishmania have been shown to have defective responses to extracellular stimuli. To investigate the potential relationship of these findings to alterations in calcium-dependent signaling pathways, the regulation of [Ca2+]i concentrations was examined in human peripheral blood monocytes infected with amastigotes of Leishmania donovani. Measurements of [Ca2+]i in fura-2-loaded monocytes were made at the single cell level by microfluorimetry. In normal monocytes, resting [Ca2+]i was 56 +/- 2 nM (mean +/- SEM). In contrast, in monocytes infected with Leishmania there was an approximately twofold increase in basal [Ca2+]i (122 +/- 5 nM, p less than 0.01 vs control). Treatment of cells with pertussis toxin before infection did not abrogate infection-induced increases in basal [Ca2+]i, suggesting that this effect was not mediated via the activation of a G protein coupled to phospholipase C. However, elevated resting [Ca2+]i did correlate with increased rates of 45Ca2+ uptake by infected monocytes. As expected, in response to treatment with 10(-7) M FMLP, control monocytes showed rapid net increases in [Ca2+]i of 303 +/- 19 nM. In contrast, net transients of [Ca2+]i in infected monocytes in response to FMLP were attenuated to only 137 +/- 9 nM (p less than 0.01 vs control). This result was not related to excess buffering of [Ca2+]i in infected cells as both control and infected monocytes showed equivalent transients of [Ca2+]i in response to the calcium ionophore A23187. Rather, inhibition of agonist-induced calcium release in infected cells appeared related to defective generation of second messenger because compared to control cells labeled with myo-[2-3H]inositol, little accumulation of inositol 1,4,5-trisphosphate was detected in infected monocytes. Attenuation of inositol phosphate accumulation and calcium release in response to chemotactic peptide correlated with decreased FMLP-induced superoxide and hydrogen peroxide production by infected monocytes. These results provide direct evidence for defective regulation of [Ca2+]i and calcium-dependent signaling in Leishmania-infected monocytes and provide a basis for understanding abnormalities in activation-related responses that involve signaling through Ca(2+)-regulated pathways.
Similarities in B cell repertoire development between autoimmune and aging normal mice.
Authors: Klinman D M 
Published: December 2022

Abstract
B cell repertoire changes that characterize systemic autoimmune disease may be linked to an acceleration of normal immune aging. To examine this issue, the repertoires expressed by lupus-prone and geriatric normal mice were compared. An ELISA-spot assay was used to identify and quantitate individual lymphocytes secreting antibodies reactive with a panel of five autoantigens and three conventional Ag. Over half of autoimmune NZB and MRL/lpr mice developed repertoires biased toward the production of specific autoantibodies by 8 mo of age. The B cell repertoires expressed by normal BALB/c mice were stable over this period but developed a similar bias toward the production of autoantibodies by 18 to 22 mo of age. As both normal and autoimmune mice grew older, they expressed repertoires that increasingly diverged from those of other members of the same strain--a process whose onset and rate of development was accelerated in lupus-prone animals. By analyzing B cells from individual MRL/lpr mice at multiple time points, we found that 1) autoreactivity developed over a specific time period, 2) individual animals developed increased responsiveness against different autoantigens, and 3) this increased responsiveness persisted for life. These results suggest that the repertoires of adult autoimmune mice are generated and maintained by a process of continuous (auto)antigenic stimulation similar to that associated with normal immune aging.
Protective effects of soluble CR1 in complement- and neutrophil-mediated tissue injury.
Authors: Mulligan M S , Yeh C G , Rudolph A R , Ward P A 
Published: December 2022

Abstract
Complement activation is an important step for triggering of acute inflammatory reactions. Soluble human recombinant complement receptor type 1 (sCR1) blocks complement activation by both classical and alternative pathways. In addition to glycogen-induced peritonitis, three models of complement-dependent acute inflammatory injury have been used to assess the protective effects of sCR1: lung and dermal injury after intraalveolar or intradermal deposition of IgG immune complexes; acute lung injury resulting from intravascular activation of complement after the i.v. injection of cobra venom factor; and acute skin and lung injury (at 4 h) after thermal trauma involving 25 to 30% total body surface area. Vascular injury was quantified by increases in vascular permeability, hemorrhage, neutrophil infiltration, and, as indicated, tissue water content. Intravenous infusion of sCR1 reduced lung and dermal vascular injury in all models studied. In glycogen-induced peritoneal exudates sCR1-reduced neutrophil accumulation by 79%. In animals undergoing IgG immune complex-induced alveolitis, sCR1 treatment reduced vascular permeability and hemorrhage by 72 and 71%, respectively, and tissue accumulation of neutrophils was reduced by 68%. After cobra venom factor injection, sCR1 reduced increases in lung vascular permeability by 67%, hemorrhage by 73%, and lung myeloperoxidase content by 55%. Four hours after thermal injury of skin, sCR1-treated animals demonstrated significant protection against lung injury; increases in vascular permeability and hemorrhage were reduced by 45 and 46%, respectively, and myeloperoxidase content was lowered by 39%. In thermal injury of the skin, sCR1 injection reduced dermal vascular permeability by 25% at 1 h (p = NS) and 44% at 4 h. Water content in skin biopsies was also decreased. There was a dose-response relationship between the amount of sCR1 infused and the extent of protection in each of the injury models. These data demonstrate that sCR1 offers significant protection against complement-dependent tissue injury in the animal models studied and that the protective effects are related to reduced neutrophil content.
Type I IL-1 receptor blockade exacerbates murine listeriosis.
Authors: Havell E A , Moldawer L L , Helfgott D , Kilian P L , Sehgal P B 
Published: December 2022

Abstract
It was found that IL-1 is produced in livers and spleens of mice shortly after the i.v. injection of a sublethal or lethal Listeria monocytogenes inoculum. In sublethally infected mice, IL-1 was present in infected livers and spleens by the end of the first day of infection. Thereafter, the amounts of IL-1 in these organs increased and decreased in concordance with bacterial numbers. IL-1 was not present in the peripheral circulation of mice during sublethal listeriosis, but was present in the blood late in lethal infection. Evidence showing that IL-1 plays a role in antibacterial resistance early in listeriosis was obtained through the use of 35F5 mAb that binds to the murine type I IL-1R and functions to block IL-1 alpha and IL-1 beta actions. Blockade of the type I IL-1R by the 35F5 mAb results in greatly enhanced bacterial growth in the livers and spleens of mice that had received a sublethal Listeria inoculum. Consistent with the exacerbation of listeriosis caused by 35F5 mAb, but in contrast to the effect of 35F5 mAb in other murine models, 35F5 mAb-treated mice exhibit markedly elevated levels of IL-6 in their circulation and infected organs.
"Universal" T helper cell determinants enhance immunogenicity of a Plasmodium falciparum merozoite surface antigen peptide.
Authors: Kumar A , Arora R , Kaur P , Chauhan V S , Sharma P 
Published: December 2022

Abstract
Synthetic peptide constructs containing a limited number of epitopes are being currently investigated as subunit vaccines against a variety of pathogens. However, because of widespread nonresponsiveness to most such constructs, possibly attributable to MHC restriction, the choice of appropriate carrier molecules to enhance immunogenicity of peptides constitutes an important and essential aspect of designing synthetic immunogens for human use. Widely used vaccines such as tetanus toxoid (TT) have not been uniformly effective as carrier proteins because of the phenomenon of epitope-specific suppression in which induction of an immune response against a synthetic peptide conjugated to TT is prevented by preexisting immunity to TT. Recently, T cell determinants that can be recognized in the context of several class II MHC molecules have been identified in tetanus toxin as well as in the circumsporozoite protein of a human malarial parasite, Plasmodium falciparum. Such determinants can be potentially used to circumvent the problem of epitope-specific suppression. In the present study we evaluated two such T cell determinants, viz., tt830-844 from tetanus toxin and CST3 from the malarial parasite, for their ability to help induce a boostable antibody response and to overcome genetic nonresponsiveness to a synthetic 20-residue construct containing a B cell and an overlapping T cell epitope from a major merozoite surface protein of P. falciparum. Our data provide support for the view that widely recognized T cell determinants may be used as universal carrier molecules for general vaccination.
Monoclonal autoantibodies to subnucleosomes from a MRL/Mp(-)+/+ mouse. Oligoclonality of the antibody response and recognition of a determinant composed of histones H2A, H2B, and DNA.
Authors: Losman M J , Fasy T M , Novick K E , Monestier M 
Published: December 2022

Abstract
MRL/Mp(-)+/+ mice produce antinuclear antibodies and develop a spontaneous autoimmune syndrome with lupus-like nephritis. We obtained a panel of seven histone-reactive IgG mAb from a single MRL/Mp(-)+/+ mouse. These antibodies do not react significantly with DNA or individual histones, but bind strongly to the histone H2A-H2B dimer and even more strongly to the H2A-H2B-DNA complex. These antibodies also bind to whole nuclei when tested by immunofluorescence, indicating that they recognize an epitope accessible in chromatin. The V region sequences of these antibodies have been determined. The H chain third complementarity-determining regions of these antibodies are similar to those found in anti-DNA antibodies even though the antibodies in our panel do not react with DNA in the absence of histones, suggesting that DNA is part of the subnucleosome epitope. Several of these antibodies are clonally related, supporting the hypothesis that the activation of these clones is Ag-driven. Analysis of the sequences of these antibodies indicates that they derive from autoreactive B cells that were clonally expanded and whose V region genes have undergone numerous somatic mutations.
Extrathymic T cell maturation. Phenotypic analysis of T cell subsets in nude mice as a function of age.
Authors: Kennedy J D , Pierce C W , Lake J P 
Published: December 2022

Abstract
T cell maturation in an extrathymic environment has been studied using as a model the congenitally athymic nude mouse. Phenotypic analyses as a function of age were conducted on lymphocytes obtained from the spleens and lymph nodes of nude mice through use of mAb recognizing T cell surface markers and multiparameter flow cytometry. The data show that nude mice accumulate increasing numbers of lymphocytes bearing Thy-1, CD3, CD4, and CD8 with age characterized by a progression from heterogeneous dim to more homogeneous bright expression. In contrast, the expression of heat-stable Ag (HSA), a marker of immature thymocytes, decreases with age. By analogy to intrathymic maturation, spleens and lymph nodes in nude mice contain T cells defined as immature, transitional, and mature based on the expression of these markers. Although the proportion of CD4+ and CD8+ T cells associated with bright CD3 expression increases with age, at no age are significant numbers of CD4+8+ cells observed, in contrast to intrathymic T cell maturation. In addition to the frequently observed inversion in the ratio of CD4 to CD8, the CD8 T cell subpopulation in older nude mice contains mainly mature cells (CD8+, CD3+, HSA-) whereas only 50% of CD4+ T cells express the mature (CD4+, CD3+, HSA-) phenotype. At any age, the spectrum of phenotypes observed indicates that lymph nodes contain more mature T cells than spleen, suggesting a role for environmental Ag in driving extrathymic maturation, a process occurring most efficiently among CD8+ T cells. Because extrathymic maturation mirrors some but not all aspects of the intrathymic pathway, we propose that the nude mouse may be a useful model for further dissecting those interactions crucial to establishing the T cell repertoire in euthymic individuals as well as elucidating the contribution of extrathymically derived T cells to the peripheral immune system.
Recombinant oncostatin M stimulates the production of acute phase proteins in HepG2 cells and rat primary hepatocytes in vitro.
Authors: Richards C D , Brown T J , Shoyab M , Baumann H , Gauldie J 
Published: December 2022

Abstract
Acute inflammation is characterized by increased liver output of acute phase proteins (APP). Several cytokines including IL-6, leukemia inhibitory factor, and IL-11 are capable of stimulating APP synthesis by hepatocytes and hepatoma cells. We have tested the activity of a separate and unique cytokine oncostatin M (OM) and have found potent APP-inducing activity of human recombinant OM on hepatocytes. OM acted in a dose-dependent fashion (ED50 5 to 10 ng/ml) in stimulating APP synthesis in human HepG2 cells, rat H35 cells, and primary rat hepatocyte cultures, but not human Hep3B cells. Human OM induced equivalent to or greater responses than IL-6 in HepG2 cells, however, it was less effective than human IL-6 in stimulating rat cells. Northern analysis showed that OM stimulated mRNA levels of haptoglobin and alpha 1-antichymotrypsin in HepG2 cells. OM induced CAT activity in HepG2 cells transfected with CAT constructs containing IL-6-responsive elements, suggesting that OM induces transcription of native proteins through mechanisms involving IL-6-responsive element-like sequences in gene promoters. OM was also shown to act additively with IL-6 or leukemia inhibitory factor and synergistically with glucocorticoid or IL-1 in the induction of specific APP. These results suggest that OM plays a role as a mediator of APP synthesis in inflammatory responses.
Evidence that leukosialin, CD43, is intensely sulfated in the murine T lymphoma line RDM-4.
Authors: Wilson A P , Rider C C 
Published: December 2022

Abstract
Metabolic labeling of the murine T lymphoma cell line RDM-4 with [35S] sulfate results in intense incorporation into a cell-retained component of apparent Mr approximately 100,000. This macromolecule is identified as a glycoprotein by lectin chromatography. The sulfate is not incorporated as tyrosine sulfate. Release of the radiolabel by alkaline beta-elimination but not by endoglycosidase F is consistent with the sulfation of O- rather than N-linked oligosaccharides. The sulfated glycoprotein displays anomalous migration on SDS-PAGE in two respects: 1) the apparent Mr shifts from 115,000 to 87,000 on increasing the acrylamide concentration from 7 to 12%, and 2) on neuraminidase digestion migration is substantially reduced (apparent Mr 140,000). These properties indicate that the sulfated protein is both heavily glycosylated and extensively sialylated, and are characteristic of the lymphoid mucin, leukosialin (sialophorin, CD43). Specific labeling of the sialoglycoproteins of RDM-4 cells indicates that leukosialin, the most intensely labeled protein, comigrates with the sulfated protein on SDS-PAGE at varying acrylamide concentrations. Our data are therefore consistent with sulfation of at least some of the numerous O-linked oligosaccharides of this abundant glycoprotein in RDM-4 cells. No sulfation of CD43 in resting splenic T cells is observed.
Regulation of synthesis of p34cdc2 and its homologues and their relationship to p110Rb phosphorylation during cell cycle progression of normal human T cells.
Authors: Lucas J J , Terada N , Szepesi A , Gelfand E W 
Published: December 2022

Abstract
In yeast, the protein kinase p34cdc2 plays a role in regulating both the G2 to M and G1 to S phase transitions. The discovery of multiple homologues of the protein in cells of higher eukaryotic organisms suggests that different cell cycle regulatory events may be performed by different kinases in such cells. Here, the synthesis and metabolism of the human forms of these proteins are described in a normal human cell type, peripheral blood T lymphocytes that have been stimulated to enter the cell cycle in vitro. Using a carboxyl-terminus antiserum specific for true p34cdc2, the protein could first be found in T cells at about 24 to 30 h after stimulation, just before the initiation of DNA synthesis. Three forms of the enzyme could be resolved by denaturing gel electrophoresis: an unphosphorylated form with an apparent molecular mass of 34,500 daltons and two phosphorylated derivatives. In cells synchronized at G2/M phase with nocodazole, p34 was almost entirely in the unphosphorylated form whereas the phosphorylated derivatives were more predominant in cultures arrested at the G1/S border with aphidicolin. The relationship of p34 synthesis to the phosphorylation of p110Rb, an event known to be associated with passage through late G1 and/or the G1/S phase transition, was also investigated. It was noted that p110Rb phosphorylation began before p34 synthesis first became detectable. Furthermore, it appeared that the two events could be largely uncoupled by treating cells with deferoxamine (10 microM), an iron chelating agent that arrests T cells at a point in late G1 phase but substantially before the G1 to S phase transition. Under these conditions, p110Rb phosphorylation was almost completely accomplished in the absence of significant p34 synthesis, a finding that suggests that most or all of p110 phosphorylation is performed by kinases other than p34. Because of this observation, extracts were next examined for p34-like molecules using an antibody against the so-called PSTAIRE domain found in all cdc2 homologues identified to date. A species of protein with a mobility slightly less than true p34 was found, even in resting T cells. Upon stimulation, this protein increased slightly in amount, and a second protein with a mobility greater than p34, a putative p33cdk2, was seen. Not only was the appearance of these proteins not inhibited by deferoxamine but they accumulated in cultures treated with the drug, suggesting that p33, and not p34, may be the G1 phase kinase for p110Rb.(ABSTRACT TRUNCATED AT 400 WORDS)
Comparison of the opsonic and complement triggering activity of human monoclonal IgG1 and IgM antibody against group B streptococci.
Authors: Shyur S D , Raff H V , Bohnsack J F , Kelsey D K , Hill H R 
Published: December 2022

Abstract
We have compared the opsonic and complement-triggering activity of transfectoma-derived, class-switched human IgG1 and IgM mAb (HumAb) against types Ia, II and III group B streptococci (GBS). These antibodies appear to be directed against the common group B cell wall Ag of these organisms. The HumAb IgM promotes uptake of type Ia and II GBS at concentrations as low as 37 ng/ml and type III GBS at concentrations of 150 ng/ml in the presence of human neonatal complement. In contrast, the IgG1 GBS HumAB showed no detectable opsonic activity in concentrations up to 600 ng/ml. When the concentration of HumAb IgG1 is raised to 2.5 micrograms/ml, significant opsonic activity against GBS is detected and when the concentration is approximately 40 micrograms/ml, the opsonic activity peaked at a slightly higher level than that with the HumAb IgM. Thus, approximately 100- fold higher concentrations of the IgG1 than the IgM HumAb are required for optimal opsonization. The opsonic activity of the IgM and IgG1 HumAb are closely related to their ability to consume complement and deposit C3 on the surface of type Ia, II, and III GBS (r = 0.959). We believe that the marked opsonic and protective activity of the IgM GBS HumAb is due to its enhanced avidity and ability to trigger the complement system. Further studies are indicated to determine the feasibility of employing human IgM antibody preparations in the immunotherapy of neonatal GBS disease.
Role of Th-1 lymphocytes in the development of protective immunity against Mycobacterium leprae. Analysis of lymphocyte function by polymerase chain reaction detection of cytokine messenger RNA.
Authors: Walker K B , Butler R , Colston M J 
Published: December 2022

Abstract
The patterns of lymphokine mRNA expression during the development of protective immunity to Mycobacterium leprae after intradermal vaccination of mice with killed M. leprae were studied. Using a polymerase chain reaction-based technique for detecting mRNA expression in small numbers of cells, we observed changes in the mRNA expression of a number of cytokine genes in the lymph nodes draining the site of vaccination. In particular, IL-1 (-alpha and -beta), IL-2, TNF (-alpha and -beta), and IFN-gamma mRNA were readily detected, whereas IL-3, IL-4, IL-5, IL-6, IL-7, and granulocyte-macrophage colony-stimulating factor mRNA were not detected, or were detectable only at very low levels. This is consistent with the selective activation of Th-1 Th cells. The effect of in vitro exposure of these cells to the immunizing Ag was also investigated; again, IL-1, IL-2, TNF, and IFN-gamma mRNA were abundant, but in addition, IL-3, IL-6, and granulocyte-macrophage colony-stimulating factor mRNA were greatly increased, suggesting an important role in the recall response.