bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antigen presentation in the central nervous system. The inhibitory effect of IL-10 on MHC class II expression and production of cytokines depends on the inducing signals and the type of cell analyzed.
Authors: Frei K , Lins H , Schwerdel C , Fontana A 
Published: December 2022

Abstract
Cells of the macrophage lineage are required to cope with bacterial infection and to serve as APC for T lymphocytes. Among the regulatory factors limiting the macrophage response to infection and the expansion of Ag-specific T cells, IL-10 has received recent attention. On monocytes/macrophages, IL-10 has been shown to inhibit the intracellular killing of bacteria, the secretion of cytokines, and the expression of MHC molecules. In the present study we have examined the effect of IL-10 on different APC obtained from the central nervous system. Both, astrocytes and microglial cells are in a resting state and require activation signals to express MHC class II and cytokine genes. Whereas IL-10 profoundly inhibits the IFN-gamma-induced expression of MHC class II Ag on microglial cells, it had no such effects on astrocytes. Nevertheless, IL-10 suppressed the MHC class II- and Ag-dependent proliferative response of T cells in the presence of both types of APC. As shown by the use of anti-IL-10 Abs, endogenously produced IL-10 influenced the function of microglia but not of astrocytes to serve as APC. IL-10 significantly inhibited the LPS-induced production of granulocyte-macrophage-CSF, macrophage-CSF, and IL-6 by both astrocytes and microglial cells. In contrast, the secretion of these cytokines by the two glial cell population was not altered by IL-10 when IL-1 beta, TNF-alpha, or viruses were used as stimuli.
HLA class I molecules are not transported to the cell surface in cells infected with herpes simplex virus types 1 and 2.
Authors: Hill A B , Barnett B C , McMichael A J , McGeoch D J 
Published: December 2022

Abstract
To assess the effect of herpes simplex virus (HSV) on assembly and transport of class I MHC molecules, we compared class I MHC immunoprecipitated from metabolically labeled infected and uninfected human dermal fibroblasts. The immunoprecipitates were analyzed by isoelectric focusing, allowing identification of individual class I alleles and assessment of transport through the Golgi apparatus by the sialation of carbohydrate residues. In cells infected with wild-type HSV, class I synthesis was reduced or abolished because of the host protein synthesis shutoff function of the UL41 gene product. In cells infected with mutant viruses of both HSV-2 strain G and HSV-1 strain 17 that lack the UL41 gene, class I HLA molecules failed to become sialated, suggesting that they were not transported to the Golgi apparatus. In contrast, transferrin receptor was normally sialated in both infected and uninfected cells. Drug treatments of cells to restrict viral gene expression suggested that an early gene or genes were responsible for the effect. A pulse chase showed that class I molecules were synthesized in normal amounts in infected cells, but that heavy chains were retained in a sialyl transferase negative compartment either stably associated with beta 2m or as free heavy chain in a pattern that is characteristic for each class I allele. HSV is thus the fourth example of a DNA virus that interferes with class I assembly or transport.
CD9-regulated adhesion. Anti-CD9 monoclonal antibody induce pre-B cell adhesion to bone marrow fibroblasts through de novo recognition of fibronectin.
Authors: Masellis-Smith A , Shaw A R 
Published: December 2022

Abstract
The modulation of adhesive interaction between lymphocyte progenitors and bone marrow stroma may critically determine the maturation and migration of B cell progenitors. mAb against CD9 and beta 1 integrins are reported to induce the homotypic adhesion of pre-B cells. We present evidence that the anti-CD9 mAb 50H.19 and ALB6 but not the proaggregatory anti-VLA-4 mAb 44H6 also enhance the Fc-independent heterotypic adhesion of the human pre-B cell lines NALM-6 and HOON to bone-marrow stromal fibroblasts (BM-FB) but not to bone marrow stroma. CD9-enhanced binding of NALM-6 cells to BM-FB was inhibited 58% by the anti-VLA-4 mAb HP2/1, 36% by the anti-VLA-5 mAb BIIG2, and 99% by their combination. The mAb effectively inhibited adhesion when prebound to NALM-6 cells but not when prebound to BM-FB. The anti-VCAM-1 mAb E1/6 inhibited CD9-enhanced adhesion by only 14% suggesting the involvement of other ligands. Adhesion was inhibited by mAbs against the COOH-terminus and central cell binding domains of fibronectin, as well as by the corresponding CS1 and RGD peptides. Adhesion was not affected by H-7 and sphingosine, inhibitors of protein kinase C. These results suggest that perturbation of CD9 on pre-B cells promotes recognition of stromal cell fibronectin by VLA-4 and VLA-5 and implicates CD9 as a novel regulator of inside-out signaling relevant to B lymphopoiesis.
Hypercross-linking surface IgM or IgD receptors on mature B cells induces apoptosis that is reversed by costimulation with IL-4 and anti-CD40.
Authors: Parry S L , Hasbold J , Holman M , Klaus G G 
Published: December 2022

Abstract
Cross-linking of sIgM or sIgD receptors on mature B cells with appropriate anti-Ig Abs normally induces B cell activation and DNA synthesis. We show here that hypercross-linking of either class of sIg receptor on these cells by biotinylated, normally mitogenic anti-mu or anti-delta mAb by avidin rapidly induces unresponsiveness to heterologous anti-Ig, accompanied by DNA fragmentation characteristic of apoptosis. Apoptotic nuclei can be detected within 4 h after stimulation, but cells that survive for 12 to 16 h are abortively activated, as evidenced by increased levels of MHC class II Ags. Because the induction of B cell tolerance is known to be modulated by T cell-derived influences, we investigated the effects of two stimuli--IL-4 and ligation of CD40--that are known to affect B cell survival in this system. IL-4 partially reversed the induction of apoptosis, as did a mAb to CD40, and both reagents together caused almost complete reversal. We therefore conclude that in the absence of T cell help the extent of sIg receptor cross-linking on mature B cells determines whether the cells enter cycle or become deleted. We believe that this system represents a polyclonal model of clonal deletion of mature B cells induced by highly cross-linking Ags, such as type 2 T-independent polysaccharide Ags.
Binding of C3b and C4b by the CR1-like site in murine CR1.
Authors: Kalli K R , Fearon D T 
Published: December 2022

Abstract
We determined whether the six short consensus repeats (SCRs) that are appended to the amino terminus of murine CR2 to form murine CR1 contain a binding site for C4b in addition to that for C3b, and whether these sites overlap or are distinct. Human K562 transfectant cell lines were established that stably expressed constructs encoding variable combinations of these six murine SCRs attached to the amino terminus of a truncated form of human CR2 lacking its iC3b/C3dg binding site. These cell lines, and two others expressing full-length human CR1 and SCRs lacking its iC3b/C3dg binding site. These cell lines, and two others expressing full-length human CR1 and SCRs 8-11 of the C3b binding site of human CR1, respectively, were assessed for their capacity to form rosettes with sheep E bearing rat C4b or guinea pig C3b. K562 cells with full length human CR1 formed rosettes with both EC3b and EC4b, and the cells expressing the construct with human CR1 SCRs 8-11 bound only EC3b. The murine CR1/human CR2 chimera containing murine SCRs 1-6 resembled the full length human CR1 in binding both EC3b and EC4b. Deletion of SCRs 5-6 from the murine CR1/human CR2 chimera diminished in parallel, but did not abolish, binding of EC3b and EC4b. Constructs containing SCRs 2-5, SCRs 3-6, or SCRs 2-6 lacked activity, indicating an absolute requirement for SCR-1 for binding of both C3b and C4b. Therefore, murine CR1 binds both C3b and C4b, and the sites for these ligands have similar, if not identical, amino- and carboxyl-terminal boundaries.
Intracellular infection by Leishmania donovani inhibits macrophage apoptosis.
Authors: Moore K J , Matlashewski G 
Published: December 2022

Abstract
The phagocytic macrophage plays a critical role in host immune responses to microbial infection, and represents a major source of inflammatory and growth cytokines. Intramacrophage infection by the protozoan parasite Leishmania donovani results in increased viability of the host cell in the absence of exogenous growth factor. We demonstrate that infection of bone marrow-derived macrophages (BMMs) by L. donovani promastigotes or treatment of BMMs with lipophosphoglycan LPG, the major surface molecule of the promastigote, inhibits apoptosis in the macrophage induced by the removal of macrophage (M)-CSF. This effect was also achieved by supernatants collected from L. donovani-infected macrophages, implicating the elaboration of a soluble factor by infected cells as the mediator of this inhibition. To identify candidate factors, reverse transcription PCR was employed to characterize the mRNA cytokine profile of infected macrophages. L. donovani infection of BMMs was found to induce gene expression for granulocyte-macrophage CSF, TNF-alpha, TGF-beta, and IL-6, but not M-CSF or IL-1 beta. Of the cytokines induced by L. donovani, rTNF-alpha and recombinant granulocyte-macrophage CSF were shown to inhibit apoptosis of BMMs induced by the removal of M-CSF. The amount of these cytokines in L. donovani-infected cell supernatants was quantified by ELISA. The mechanism by which L. donovani may inhibit apoptosis is discussed.
Immunoreactivity and function of oligosaccharides in cobra venom factor.
Authors: Gowda D C , Petrella E C , Raj T T , Bredehorst R , Vogel C W 
Published: December 2022

Abstract
Cobra venom factor (CVF) is the nontoxic C-activating glycoprotein in cobra venom. It is a structural and functional analogue of complement component C3. Previous work has established that the major oligosaccharide chain of CVF is a symmetric fucosylated biantennary complex-type N-linked chain containing an alpha-galactosylated Le(x) antigenic epitope, Gal alpha 1-3Gal beta 1-4 (Fuc alpha 1-3) GlcNAc beta 1, a novel carbohydrate structure. We show that naturally occurring anti-alpha-Gal Ab present in normal human serum binds to CVF. In view of a possible human application of CVF, we studied the effect of this anti-alpha-Gal Ab on CVF function as well as the effect of oligosaccharide modification or removal on CVF activity and immunoreactivity with the anti-alpha-Gal Ab. The immunoreactivity of CVF with the anti-alpha-Gal Ab is abolished upon de-alpha-galactosylation or complete deglycosylation. De-alpha-galactosylated CVF and deglycosylated CVF were found to be equally active in forming a stable C3/C5 convertase with human factor B and in decomplementing human serum indicating that the oligosaccharide chains of CVF are not required for its C-activating function. Consistent with the unaltered functional activity, deglycosylation of the molecule caused only minor changes in secondary structure as judged by far UV circular dichroism analysis. However, the oligosaccharide chains appear to contribute to the thermal stability of CVF, because deglycosylation caused the molecule to be more sensitive to temperature. Inasmuch as rCVF produced in mammalian cells can be expected to contain sialylated oligosaccharide chains, we also prepared sialylated CVF by enzymatic sialylation of de-alpha-galactosylated and de-alpha-fucosylated CVF with 2,6-sialyltransferase. It was found that the secondary structure and the activity of sialylated CVF were unchanged compared to native CVF.
Sublytic complement attack exposes C-reactive protein binding sites on cell membranes.
Authors: Li Y P , Mold C , Du Clos T W 
Published: December 2022

Abstract
C-reactive protein (CRP) is an acute phase serum protein synthesized by the liver. CRP has been localized to acute inflammatory sites and has been postulated to facilitate the removal of damaged cells. CRP binds to a number of ligands that may be present in inflammatory sites, and the extent to which individual ligands are involved in its binding to tissue sites is unknown. Complement activation is important in the tissue damage in many inflammatory conditions causing cell membrane damage and recruitment of inflammatory cells. This paper describes the binding of CRP to complement-damaged cell membranes. Raji cells activate the alternative complement pathway resulting in the deposition of C3b and membrane attack complexes (MAC) on the cell membrane. However, Raji cells are relatively resistant to killing by human complement. Treatment of Raji cells with human serum led to calcium-dependent phosphocholine-inhibitable CRP binding. CRP binding was eliminated by depletion of C3, C5, or C8 and reduced by depletion of C9 from serum. CRP binding preceded cell death and co-localized with MAC on cell membranes. CRP binding to complement-treated liposomes required phosphatidylcholine in addition to the MAC indicating that membrane phospholipids rather than the MAC proteins provide the binding sites for CRP. However, for both liposomes and Raji cells disruption of the lipid bilayer by complement attack was required for CRP binding to occur. These results support the hypothesis that CRP binding at sites of inflammation may be mediated by exposed phospholipids on damaged cell membranes.
Mast cell and neutrophil expression of dog mast cell protease-3. A novel tryptase-related serine protease.
Authors: Yezzi M J , Hsieh I E , Caughey G H 
Published: December 2022

Abstract
In previous work the primary structure of a previously unknown protease was deduced from the sequence of a dog mastocytoma cDNA. The predicted preproprotein shares some features with mast cell tryptases but is no more than 49% identical in sequence to known trypsin-like enzymes, including dog tryptase. This study explores the expression of this protein, termed dog mast cell protease-3 (dMCP-3). A polyclonal Ab was raised to a peptide corresponding to residues 166-181 of the deduced sequence. Anti-dMCP-3(166-181) Ig recognizes dMCP-3 expressed as a CheY fusion protein in Escherichia coli and binds to a approximately 36-kDa protein in extracts of dog mastocytomas. The Ab does not recognize dog tryptase, dMCP-3s closest known relative in mastocytoma cells. When used with fluorescein-conjugated and alkaline phosphatase-conjugated secondary Abs, anti-dMCP-3(166-181) Ig yields punctate cytoplasmic staining in mastocytoma cells, suggesting localization to intracellular granules. Staining is greatly reduced by preincubation with synthetic dMCP-3 peptide, supporting the specificity of the Ab. Immunohistochemical staining of normal dog tissues reveals scattered dMCP-3 reactive cells in skin, intestine, trachea, and lung parenchyma. Double staining with Ab and methylene blue shows that anti-dMCP-3(166-188) Ig recognizes extravascular mononuclear tissue cells with metachromatic granules. In addition, cytoplasmic staining is seen in polymorphonuclear leukocytes within vessels in tissue sections and in leukocytes harvested from blood. Hybridization of dMCP-3 cDNA to dog skin RNA provides further evidence of dMCP-3 gene transcription in normal tissue. Thus, this study provides immunochemical evidence of dMCP-3 expression in dog mast cell tumors, normal tissue mast cells, and neutrophils.
Elevated in vivo and in vitro secretion of CD8-alpha molecules in patients with systemic lupus erythematosus.
Authors: Linker-Israeli M , Hyun S , Ozeri-Chen T , Wallace D J , Banks K , Klinenberg J R 
Published: December 2022

Abstract
Endogenously activated CD8+ cells contribute to the aberrant immune regulation that characterizes SLE. Because stimulation of CD8+ cells with lectin/Ag triggers release of CD8-alpha molecules (sCD8), we measured, in patients with SLE, serum sCD8 content, its correlation with disease activity, and the in vitro release of sCD8 by SLE PBMCs. sCD8 levels, measured by ELISA in sera of 50 SLE patients, were higher than normal in 16 out of 21 mildly active and 15 out of 15 active SLE patients. sCD8 correlated positively with the clinical index for disease activity (r = 0.57, p = 0.001) and with sIL-2R levels (r = 0.52, p &lt; 0.0001), and negatively with serum C3 levels (r = -0.5, p &lt; 0.04). Freshly isolated SLE PBMCs had higher than normal CD8-alpha mRNA levels and secreted high levels of sCD8 in vitro (p &lt; 0.05 vs control PBMC). sCD8 in vitro release by SLE PBMCs may be modulated by non-CD8+ cells. Thus, anti-CD2 mAb inhibited sCD8 release, whereas anti-HLA mAb increased it in unseparated PBMCs, but not in CD8+ enriched cultures. Moreover, sCD8 release increased significantly in PBMC cultures enriched for CD8+ DR+ cells by negative selection. Added-back monocytes decreased sCD8 to original levels, but not after glutaraldehyde fixation, nor in the presence of anti-HLA mAb. Further, lectin-induced IgG production and proliferation were reduced in the presence of sCD8, suggesting that the soluble CD8 molecules may be immunoregulatory. Because the high sCD8 levels in sera of active SLE likely reflect pathogenic cell activation, serum CD8 content may be an additional serologic activity marker, and its study could provide insights into mechanisms of disease.
Idiotypic intravaginal vaccination to protect against candidal vaginitis by secretory, yeast killer toxin-like anti-idiotypic antibodies.
Authors: Polonelli L , De Bernardis F , Conti S , Boccanera M , Gerloni M , Morace G , Magliani W , Chezzi C , Cassone A 
Published: December 2022

Abstract
The principles of idiotypic (Id) vaccination were used to immunize against vaginitis caused by Candida albicans, a widespread and sometimes intractable disease in women. To this aim, a murine mAb (KT4, IgG1) neutralizing in vitro the anti-Candida activity of a yeast killer toxin (YKT) was used as an Id vaccine to elicit Abs with toxin-like activity in a rat vaginitis model. Nonimmunized and isotype-matched, irrelevant mAb-immunized rats served as controls. An effective protection was obtained in Id-vaccinated animals, as demonstrated by a highly significant decrease in vaginal Candida CFU compared with controls. The protection was associated with rising vaginal titers of anti-idiotypic Abs (IdAb), prevalently of the IgA isotype, that were able to passively transfer the protective state to nonimmunized animals. The vaginal IdAb possessed YKT-like activity because they were able to kill in vitro the challenging fungal cells, and this killing was neutralized by the mAb KT4. Overall, these data demonstrate that secretory IdAb elicited by intravaginal Id vaccination with mAb KT4 protected the rats from the infectious challenge with Candida albicans by molecular mimicking YKT activity as its internal image.
B7 expression on thymic medullary epithelium correlates with epithelium-mediated deletion of V beta 5+ thymocytes.
Authors: Degermann S , Surh C D , Glimcher L H , Sprent J , Lo D 
Published: December 2022

Abstract
Recent evidence suggests that I-E+ thymic epithelium, especially medullary epithelium, can induce partial deletion of superantigen-reactive T cells expressing TcR V beta 5, V beta 11, and V beta 17. To seek further information on this issue, we constructed bone marrow chimeras in which MHC class II I-E is expressed on thymic epithelial cells at various levels and locations; the chimeras were reconstituted with stem cells from TcR V beta 5 transgenic mice. Intrathymic deletion of V beta 5 T cells was restricted to relatively mature T cells (expressing high TcR levels), and the degree of deletion correlated with the density of I-E expression in the thymic medulla rather than in the thymic cortex; selective I-E expression in medullary epithelium caused prominent deletion. Interestingly, immunostaining of normal and chimeric mice revealed that expression of B7 (the ligand for CD28) is largely restricted to a subset of medullary epithelial cells; these cells are I-E+ and co-express a specific carbohydrate bound by the lectin UEA-1. B7 expression was lower in thymuses of class II-deficient mice (A beta b-/-) and T-cell-deficient mice (SCID), suggesting that B7 expression is up-regulated during CD4+ thymocyte selection. In support of this idea, B7 expression in the thymus was restored to a normal level in bone marrow reconstituted SCID mice. Because B7 expression correlates with a costimulatory signal for T cells, selective expression of B7 and related antigens on I-E+ medullary epithelium may explain why these cells play a more prominent role in V beta deletion than cortical epithelium.
Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo.
Authors: Hamann A , Andrew D P , Jablonski-Westrich D , Holzmann B , Butcher E C 
Published: December 2022

Abstract
Lymphocyte recirculation through different organs is thought to be regulated by adhesion molecules ("homing receptors") recognizing tissue-specific vascular addressins on endothelium. Here we show that the alpha 4/beta 7-integrin has a key role in the migration of mouse lymphocytes to mucosal sites. Homing to Peyer's patches but not to peripheral lymph nodes is inhibited by Fab fragments of mAb PS/2 against the alpha 4-integrin chain, by mAb DATK32 recognizing a combinatorial epitope on the alpha 4/beta 7-integrin, and by mAb FIB30 against the beta 7-chain. The Abs significantly reduce homing of lymphocytes to the intestine, as well. The migration of immunoblasts to gut and gut-associated lymphoid tissue also involves the alpha 4/beta 7-integrin heterodimer. Another anti-alpha 4 Ab, R1-2, which blocks lymphocyte binding to Peyer's patches in the Stamper-Woodruff frozen section assay and lymphocyte adhesion to VCAM-1 and fibronectin, has only minor effects on lymphocyte traffic in vivo. Anti-VCAM-1 Ab as well as the fibronectin peptide CS-1 are without influence on the migration to Peyer's patches or intestine, in contrast to Ab against the mucosal addressin MAdCAM-1. Thus, homing to gut-associated sites is regulated by the alpha 4/beta 7-integrin heterodimer interacting with the vascular addressin, MAdCAM-1, and not with fibronectin or VCAM-1 as counterstructures. Inhibition of homing to Peyer's patches and intestine by the anti-integrin Abs studied was only partial. L-selectin also participates in the homing of small lymphocytes to mucosal sites, especially Peyer's patches, but does not contribute substantially to the localization of blasts into the intestinal wall. The results support a major, but not exclusive role of the alpha 4/beta 7-integrin in lymphocyte traffic to mucosal sites.