bluuebunny/crossref_metadata_2025_split huggingface dataset:
NK cell receptor calibration: effects of MHC class I induction on killing by Ly49Ahigh and Ly49Alow NK cells.
Authors: Olsson-Alheim M Y , Salcedo M , Ljunggren H G , Kärre K , Sentman C L 
Published: December 2022

Abstract
NK cells from C57BL/6 (B6) mice and H-2Dd transgenic B6 (D8) mice express different levels of the inhibitory receptor Ly49A, and they also differ in their target cell specificity. Here, we examined this differential specificity with respect to the role of the Ly49A receptor expression on effector cells and levels of H-2Dd inhibitory ligands on target cells. NK cells from D8 mice express low levels of Ly49A receptor (Ly49Alow), and are able to kill SP2/0 tumor cells in spite of their expression of H-2Dd. H-2Dd is expressed at reduced levels on SP2/0 cells; when these were increased three- to fivefold after IFN-gamma treatment, the killing by Ly49Alow NK cells from D8 mice was markedly reduced. Efficient killing was restored when the effectors were preincubated with anti-Ly49A F(ab')2 Abs. A separate experimental system was based on D8 TAP1-deficient Con A blasts exogenously loaded with H-2Dd-specific peptides. In this system, higher levels of cell surface H-2Dd had to be induced by peptide to inhibit D8 Ly49Alow NK cells to an extent similar to that of B6 Ly49Ahigh NK cells. Ly49A receptors on NK cells from H-2Dd transgenic mice are thus functional, although they require high levels of ligand to inhibit progression of the NK-target cell interaction. The data are in favor of the "receptor-calibration" model, which suggests that down-regulation of inhibitory receptors on NK cells may be useful in order for NK cells to discriminate between normal and reduced levels of MHC class I molecules.
Down-regulation of the expression and function of the transporter associated with antigen processing in murine tumor cell lines expressing IL-10.
Authors: Salazar-Onfray F , Charo J , Petersson M , Freland S , Noffz G , Qin Z , Blankenstein T , Ljunggren H G , Kiessling R 
Published: December 2022

Abstract
The MHC class I molecules present antigenic peptides to CTL. The peptides are delivered to the secretory pathway by TAP, which is formed by the association of MHC-encoded TAP1 and TAP2 gene products. Tumor cells incubated or transfected with IL-10 had decreased but peptide-inducible expression of MHC class I, decreased sensitivity to MHC class I-restricted CTL, and increased NK sensitivity. We here demonstrate that IL-10 expression in the murine lymphoma RMA inhibits the TAP-dependent translocation of peptides to the endoplasmic reticulum, resulting in accumulation of immature MHC class I molecules in the endoplasmic reticulum and subsequently low expression of cell surface MHC class I molecules. This finding is explained by a down-regulation of expression of TAP1 and TAP2, observed in IL-10-transfected RMA cells as well as in IL-10-transfected P815 mastocytoma cells. In the J558L plasmacytoma cell line, constitutively expressing high levels of IL-10, increased TAP-dependent translocation of peptides and expression of cell surface MHC class I could be induced by IL-10 antisense expression. IL-10 is the first example to demonstrate that a cytokine can decrease the expression and function of the TAP1/2 molecular complex and, in more general terms, the first example of a cytokine with an inhibitory effect on MHC class I-mediated Ag presentation.
Human herpesvirus 7 induces the down-regulation of CD4 antigen in lymphoid T cells without affecting p56lck levels.
Authors: Secchiero P , Gibellini D , Flamand L , Robuffo I , Marchisio M , Capitani S , Gallo R C , Zauli G 
Published: December 2022

Abstract
In this study, we investigated the fate of the CD4 Ag during infection of CD4+ T cells with the T lymphotrophic human herpesvirus 7 (HHV-7), using the SupT1 lymphoblastoid T cell line as a model system. The following points were established: 1) productive infection with HHV-7 was required to obtain persistent down-modulation of surface CD4 (CD4SURF); 2) at 6 to 9 days postinfection, when approximately 50 to 60% of SupT1 cells still showed a CD4SURF dim positivity, a drastic loss of total CD4 protein was found by either Western blot or immunoprecipitation experiments; 3) a block in CD4 protein production was demonstrated by a radioimmunoprecipitation assay; 4) analysis of the mRNA steady-state levels and transfection studies performed with a plasmid containing the CD4 promoter/enhancer regions in front of the luciferase gene indicated that HHV-7 infection has a suppressive effect on CD4 transcription; 5) both CD4SURF and intracellular CD4 (CD4INTRA) were reduced in HHV-7-infected cells with respect to uninfected controls, but the loss of CD4SURF was more dramatic than that of CD4INTRA; 6) immunogold labeling and electron microscopy demonstrated that CD4INTRA co-localized with HHV-7 Ags within the same subcellular compartments of infected cells; and 7) the total amount of the tyrosine kinase p56lck and tyrosine phosphorylated p56lck levels were unchanged in HHV-7-infected versus uninfected cells.
Ligation of L-selectin on T lymphocytes activates beta1 integrins and promotes adhesion to fibronectin.
Authors: Giblin P A , Hwang S T , Katsumoto T R , Rosen S D 
Published: December 2022

Abstract
Lymphocyte recirculation is dependent on families of adhesion molecules expressed on lymphocytes and their sequential interaction with ligands expressed on high endothelial venules in secondary lymphoid organs such as peripheral lymph nodes. By binding its carbohydrate-based ligands, L-selectin initiates this cascade of molecular interactions, supporting the rolling of lymphocytes along high endothelial venules. Subsequent activation of lymphocyte integrins leads to cell arrest followed by lymphocyte extravasation. Here, we demonstrate stimulated adhesion of PBL and Jurkat T cells to immobilized fibronectin following treatment with (1) GlyCAM-1, a physiologic ligand for L-selectin, and (2) cross-linked anti-L-selectin mAbs. We also utilize a solution binding assay to detect early changes in integrin activity, including affinity modulation and/or integrin clustering, and distinguish these from later postreceptor binding events such as changes in cell shape and spreading. With the Jurkat cell line, GlyCAM-1 and fucoidin (an L-selectin ligand mimetic) induce the binding of soluble fibronectin. In contrast, stimulation through the Jurkat TCR fails to promote binding to soluble ligand even though TCR cross-linking markedly enhances adhesion to immobilized fibronectin. These data suggest that L-selectin and the TCR promote adhesion through distinct mechanisms. Finally, we demonstrate that beta1 integrins are preferentially activated on naive T cells through the L-selectin pathway. Together with our previous studies showing similar activation of beta2 integrins on the naive T cell subset, these data suggest that signals delivered though L-selectin participate in the preferential recruitment of these cells to peripheral lymph nodes.
Colchicine down-regulates lipopolysaccharide-induced granulocyte-macrophage colony-stimulating factor production in murine macrophages.
Authors: Rao P , Falk L A , Dougherty S F , Sawada T , Pluznik D H 
Published: December 2022

Abstract
Activation of macrophages by LPS and taxol results in production of IL-1, IL-6, TNF-alpha, and granulocyte-macrophage CSF (GM-CSF), which are involved in regulating hemopoiesis, inflammation, and immune responses. Microtubules are proposed as a target site for LPS interaction(s), based on similarities between the effects of the tubulin-binding drug taxol and LPS. To clarify the role of microtubules in LPS-induced GM-CSF expression in macrophages, we examined whether microtubule depolymerizing agents affect GM-CSF production in macrophages. Pretreatment with colchicine impaired LPS induction of GM-CSF in RAW 264 cells, and studies using stable transfectants revealed that colchicine impaired the transcriptional responsiveness of a reporter gene driven by a GM-CSF promoter sequence. Colchicine inhibition of the GM-CSF response correlated with decreases in the mRNA levels of beta-tubulin; maximal inhibition of both events was observed 4 h after addition of colchicine. Microtubule agents inhibited LPS induction of IL-6 and TNF-alpha, while the induction of both IL-1beta and inducible nitric oxide synthase was unaltered, suggesting that LPS activates microtubule-dependent and -independent pathways. Interestingly, LPS stimulation of macrophages down-regulated levels of beta-tubulin transcripts, implying that LPS interacts with an element(s) of the microtubule network in vivo, activating pathways regulating transcription of beta-tubulin. The ability of both colchicine and LPS to modulate transcription of beta-tubulin suggests that this event does not per se underlie the inhibitory effect of colchicine on LPS-induced GM-CSF expression. These data led us to conclude that colchicine inhibits LPS induction of GM-CSF by affecting microtubule-dependent costimulatory signaling pathways that synergize with primary LPS-triggered responses.
Alpha 1-acid glycoprotein and alpha 1-antitrypsin inhibit TNF-induced but not anti-Fas-induced apoptosis of hepatocytes in mice.
Authors: Van Molle W , Libert C , Fiers W , Brouckaert P 
Published: December 2022

Abstract
The acute phase proteins alpha 1-acid glycoprotein (alpha 1-AGP) and alpha 1-antitrypsin (alpha 1-AT) were shown to inhibit, by a mechanism unidentified to date, the lethality induced by TNF both in normal mice and in mice sensitized with galactosamine. We found that both bovine alpha 1-AGP and human alpha 1-AT also inhibited specifically the induction of apoptosis of hepatocytes by TNF/ galactosamine in vivo. This inhibition is specific for TNF, since apoptosis induced by TNF and actinomycin D was also inhibited, while similar apoptosis of hepatocytes induced by anti-Fas remained unaffected. The observation that these acute phase proteins did not affect the induction by TNF of IL-6, nitric oxide, or serum amyloid P excludes a nonselective inhibition of the TNF-activated pathways. The protection conferred by alpha 1-AGP and alpha 1-AT is presumably indirect, since these proteins did not inhibit TNF/actinomycin D-induced apoptosis in the hepatoma cell lines HepG2 and BWTG3.
Autoantibodies to IA-2 and IA-2 beta in insulin-dependent diabetes mellitus recognize conformational epitopes: location of the 37- and 40-kDa fragments determined.
Authors: Xie H , Zhang B , Matsumoto Y , Li Q , Notkins A L , Lan M S 
Published: December 2022

Abstract
IA-2 and IA-2 beta are major autoantigens in insulin-dependent diabetes mellitus (IDDM) and the precursors, respectively, of a 40-and 37-kDa tryptic fragment that reacts with IDDM sera. In the present study, by amino acid sequencing of recombinant IA-2 and IA-2 beta, we determined the tryptic cleavage sites involved in the generation of these fragments. Both cleavage sites are immediately after an arginine residue at position 653 for IA-2 and position 679 for IA-2 beta. The resulting tryptic fragments are 326 and 307 amino acids in length and retain their ability to react with IDDM sera. In contrast to IA-2 and IA-2 beta, other members of the protein tyrosine phosphatase (PTP) family (i.e., RPTP kappa, RPTPmu, NU-3, SHP, and 3CH134) are completely susceptible to digestion by trypsin. Sequence analysis revealed five conserved cysteine residues in IA-2 and IA-2 beta that are not present in other PTPs. Reduction and alkylation of IA-2 and IA-2 beta recombinant proteins resulted in loss of both resistance to digestion by trypsin and reactivity with autoantibodies in IDDM sera. It is concluded that disulfide bond formation plays a critical role in the maintenance of antigenic structure and that the autoantibodies to IA-2/IA-2 beta in IDDM sera recognize conformational epitopes.
Expression and function of OX40 ligand on human dendritic cells.
Authors: Ohshima Y , Tanaka Y , Tozawa H , Takahashi Y , Maliszewski C , Delespesse G 
Published: December 2022

Abstract
OX40 ligand (OX40L), a member of the TNF family, was shown to be capable of signaling both the cells on which it is expressed and those expressing OX40, its cognate receptor. Here we show that OX40L is expressed on dendritic cells (DC), the most efficient APC to prime naive T cells. The expression and the functional activity of OX40L were examined by means of mAbs used to stain or cross-link OX40L on 1) freshly isolated human blood DC (bDC) and 2) monocyte-derived DC at different stages of differentiation. These were derived from monocytes cultured either with IL-4 and granulocyte-macrophage CSF (IL-4-Mo-DC) or with IL-4 and granulocyte-macrophage CSF plus TNF-alpha. Both types of Mo-DC expressed OX40L after stimulation through CD40; ligation of OX40L on activated IL-4-Mo-DC enhanced by 4- to 35-fold their cytokine production (TNF-alpha, IL-12 p40, IL-1 beta, and IL-6) and increased CD80, CD86, CD54, and CD40 expression. Stimulation of activated IL-4-Mo-DC through OX40L strikingly enhanced their maturation as evidenced by CD83 up-regulation, CD115 (CSF-1R) down-regulation, and typical morphologic changes. OX40L was constitutively expressed on a subset of bDC, and its ligation slightly enhanced CD40L-stimulated IL-12 production. OX40L was down-regulated after overnight culture and spontaneously reexpressed on a subset of mature bDC (CD83high, CD33high, CD11chigh, CD5+). Thus, the expression of OX40L on DC suggests a physiologic role of this molecule during T cell priming by virtue of its ability to costimulate both T cell and DC activation and differentiation.
Clonal expansions of B lymphocytes in old mice.
Authors: LeMaoult J , Delassus S , Dyall R , Nikolić-Zugić J , Kourilsky P , Weksler M E 
Published: December 2022

Abstract
The effect of age on the diversity of the murine Ig heavy chain repertoire has been studied in unimmunized C57BL/6 mice. We examined the heterogeneity of complementarity-determining region 3 (CDR3) sizes of Ig mRNA of the IgM and IgG isotypes using two VH families, VHJ558 and VHQ52, which together account for approximately 65% of the Ab repertoire. The broad and bell-shaped profiles representing the diversity of the VHJ558 family in the spleen of 2- to 6-mo-old C57BL/6 mice becomes significantly less diverse after 12 mo of age and by 18 mo of age, single CDR3 sizes that dominate the profiles can be observed in the spleens of &gt; 85% of the mice. Readable sequences have been obtained from 40 dominant mRNA CDR3 size species indicating that they represent clonal populations of B lineage. There are no significant homologies among these sequences. Clones of B lymphocytes that express a dominant CDR3 mRNA species can also be found in the bone marrow, the mesenteric lymph nodes, and the thymus of C57BL/6 mice &gt; 18 mo of age. Some clones of B cells can be detected in only one lymphoid compartment; others are found in two or more compartments. The splenic B cell clones in C57BL/6 mice &gt; 18 mo of age are stable for at least 2 mo. The CDR3 mRNA species that dominate the splenic repertoire of Ig mRNA-expressing cells in vivo do not dominate the repertoire of splenic B cells activated in vitro by bacterial LPS, suggesting that they represent a modest population of B cells expressing high levels of Ig mRNA.
Molecular regulation of IL-6 activation by asbestos in lung epithelial cells: role of reactive oxygen species.
Authors: Simeonova P P , Toriumi W , Kommineni C , Erkan M , Munson A E , Rom W N , Luster M I 
Published: December 2022

Abstract
IL-6 has been characterized as a pleiotropic cytokine with multiple biologic activities, but its induction and role in asbestos diseases have not been studied. Asbestos fibers were found to stimulate IL-6 expression and secretion in pulmonary type II-like epithelial A549 cells as well as in normal human bronchial epithelial cells. IL-6 induction was dependent on the intracellular redox-oxidative state, since intracellular hydroxyl scavengers and N-acetylcysteine, a precursor of glutathione, abrogated IL-6 secretion by asbestos or H2O2. IL-6 induction paralleled increased DNA binding activity to the nuclear factor-kappa B (NF-kappa B)- and NF-IL-6-recognized sites in the IL-6 promoter. The NF-kappa B and NF-IL-6 DNA binding proteins were immunochemically characterized as a heterodimer p65/p50 and a homodimer C/EBP beta, respectively. Stimulation of DNA binding activity to the NF-kappa B and NF-IL-6 binding sites of the IL-6 promoter by asbestos or H2O2 were inhibited by tetramethylthiourea, a hydroxyl radical scavenger. The role of local IL-6 production in the pathophysiologic processes of fiber-induced lung disorders was examined. Although less active than fibroblast growth factor, human rIL-6 also stimulated lung fibroblast growth, as evidenced by increased [3H]thymidine incorporation. Furthermore, elevated IL-6 levels were found in bronchoalveolar lavage fluids from patients diagnosed with lung fibrosis and work-related histories of long term asbestos exposure. Taken together, the results suggest that asbestos-induced oxidative stress is involved in the activation of NF-kappa B and NF-IL-6 transcription factors, which recognize the IL-6 promoter. The resulting increase in IL-6 expression may be involved in both inflammatory and fibrotic processes in the lung.
Binding of the Epstein-Barr virus to human platelets causes the release of transforming growth factor-beta.
Authors: Ahmad A , Menezes J 
Published: December 2022

Abstract
Human platelets bear on their surface complement receptor type II (CR2), which is also the receptor for the EBV. Although the cross-linking of these receptors causes activation and aggregation of platelets, no immunologic consequence of the potential binding of EBV to these receptors on human platelets has ever been described. We report here that binding of EBV to human platelets causes the release of TGF-beta from the latter. Both infectious and UV-inactivated noninfectious viral particles can mediate this release. Anti-CR2 mAb OKB7, which blocks the binding of EBV to CR2, also blocks the EBV-mediated release of TGF-beta. Furthermore, platelets recovered from the initial incubation no longer release TGF-beta upon subsequent incubation with EBV. Since TGF-beta is a potent immunosuppressive agent, its release from platelets upon binding of EBV may play a role in the pathogenesis of EBV-associated diseases.
The association of HLA-DR alleles and T cell activation with allergic bronchopulmonary aspergillosis.
Authors: Chauhan B , Santiago L , Kirschmann D A , Hauptfeld V , Knutsen A P , Hutcheson P S , Woulfe S L , Slavin R G , Schwartz H J , Bellone C J 
Published: December 2022

Abstract
Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity lung disease caused by the mold Aspergillus fumigatus. We previously reported that the majority of T cell clones (TCC) isolated from three ABPA patients, and specific for a dominant Ag of A. fumigatus, Asp f 1, were IL-4-producing CD4+ Th2 cells capable of responding to Ag in association with the HLA-DR subtypes DRB1*1501, *1503, and *1601 for HLA-DR2, and DRB1*1101, *1104, and *1202 for HLA-DR5. In the present study we extended the previous findings to determine whether the observed restriction with the HLA-DR2/5 subtypes held importance in a larger patient population. Serotyping revealed that 16 of 18 ABPA patients were either HLA-DR2, HLA-DR5, or both. Compared with a normal control population, the frequencies of HLA-DR2 (50 vs 22.3%) and HLA-DR5 (44.4 vs 19.8%) were significantly increased in these ABPA patients. Genotype analyses of an additional 15 patients identified the same HLA-DR subtypes previously shown functional for Asp f 1 Ag presentation. The relative avidities of Asp f 1 peptides for the purified HLA-DR subtypes, DRB1*1501 (functional) and DRB1*1502 (nonfunctional), were examined to determine whether differential binding to the HLA-DR subtypes explains successful Ag presentation. Similar low binding avidities were detected for both HLA-DR subtypes, indicating that the functionality cannot be simply explained by differences in binding affinities. Thus, the limited number and their role in Ag presentation emphasizes the possibility that the six identified HLA-DR subtypes are important in the pathophysiology of ABPA.
Streptococcal cell wall-induced arthritis. Requirements for neutrophils, P-selectin, intercellular adhesion molecule-1, and macrophage-inflammatory protein-2.
Authors: Schimmer R C , Schrier D J , Flory C M , Dykens J , Tung D K , Jacobson P B , Friedl H P , Conroy M C , Schimmer B B , Ward P A 
Published: December 2022

Abstract
Immune arthritis in rat ankle joints was induced by intra-articular injection of streptococcal cell was extract (SCW), followed 21 days later by i.v. injection of SCW. This results in a monoarticular arthritis characterized by an influx of neutrophils and mononuclear cells, a 35-fold increase in urinary excretion of 8-hydroxy-deoxyguanosine (8-OH-dGUA; an index of free radical production), ankle edema, and joint damage/destruction. Neutrophil depletion substantially reduced the intensity of ankle edema. Ab-induced blockade of P-selectin or ICAM-1 also reduced the intensity of ankle edema and the influx of neutrophils. Blockade of TNF-alpha or IL-1 resulted in nearly complete and persistent reduction in ankle edema and profound reductions in the accumulation of neutrophils and mononuclear cells in affected joints. Finally, blocking of macrophage-inflammatory protein-2 reduced ankle edema and neutrophil accumulation during the first 2 days after i.v. challenge with SCW. These data indicate that SCW-induced arthritis is neutrophil dependent and that the recruitment of neutrophils and subsequent joint edema requires ICAM-1, P-selectin, and macrophage-inflammatory protein-2, as well as TNF-alpha and IL-1.
Studies in Specific Hypersensitiveness
Authors: Chobot Robert 
Published: December 2022

Abstract
The relationship of the hay fever excitants in the pollens of Bermuda grass and timothy grass is of clinical importance and to the best of our knowledge has not been studied.
When in 1923 Dr. A. Vander Veer, Jr., examined this question in several cases of timothy hay fever, he observed a similarity of the skin reactions and of the eye reactions produced by the two extracts, but he came to no definite conclusions because of some uncertainty as to the quality of the pollen extracts that he was using, and because the method of passive transfer was not employed. Dr. Vander Veer did not publish these experiments, and it was at his suggestion that the present investigation was begun.
For this study ten hay fever subjects sensitive to timothy pollen were selected whose constitutional sensitivity ranged from class A to class C, (classification of R. A. Cooke).