bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of complement activity by immunoglobulin. I. Effect of immunoglobulin isotype on C4 uptake on antibody-sensitized sheep erythrocytes and solid phase immune complexes.
Authors: Miletic V D , Hester C G , Frank M M 
Published: January 2023

Abstract
Intravenous Ig, composed principally of IgG, prevents complement attack by inhibiting C3 and C4 uptake onto target cells and tissues. Using two different models, Ab-sensitized SRBC and BSA-anti BSA solid phase immune complexes, we have examined the complement inhibitory capacity of three Ig classes (IgG, IgM, IgA) focussing on inhibition of C4 uptake. It was found that on both a weight and molar basis, monomeric serum IgA and IgM were far more active than IgG (weight efficiency ratios were 1.0, 20.8, and 236.3, and molar efficiency ratios 1.0, 24.0, and 1382.9 for polyclonal IgG, IgA1, and IgM, respectively). Monoclonal IgM were less active than polyclonal IgM (50% inhibition was achieved in SRBC model by 0.022, 0.30, 1.6, and 1.6 mg/ml of polyclonal IgM and monoclonal IgM from patients Lew, Will, and Pri). Secretory IgA was less active than serum IgA1 and similar in inhibitory activity to IgG (weight and molar efficiency ratios 1.5 and 0.6 compared with IgG). All tested preparations were less active in the solid phase immune complex model than in the sensitized cell model. A mixture of Igs of different isotypes was somewhat more active than any isotype alone. These results suggest that polyclonal serum IgA and IgM can also be considered for active therapy in diseases accompanied by the activation of classical complement pathway.
Thioredoxin as a potent costimulus of cytokine expression.
Authors: Schenk H , Vogt M , Dröge W , Schulze-Osthoff K 
Published: January 2023

Abstract
Reduction/oxidation (redox) processes have been implicated in various biologic processes, including signal transduction, gene expression, and cell proliferation. Thioredoxin is one of the major redox-regulatory molecules which because of its dithiol/disulfide exchange activity determines the oxidation state of protein thiols. In this study, we report that treatment of several cell types with thioredoxin strongly enhances the expression of various cytokines. In monocytic Mono Mac6 cells stimulated with the phorbolester tetradecanoyl phorbolacetate (TPA), thioredoxin was found to augment the expression of TNF at the protein and mRNA levels. In this and other cell lines, such as fibrosarcoma and endothelial cells, thioredoxin also dose-dependently increased the synthesis of IL-6. Treatment of TPA-stimulated Mono Mac6 cells resulted in a strong potentiation of secreted IL-1 bioactivity and expression of IL-1 alpha and IL-8 mRNA. In addition, in TPA-activated Molt-4 T cells, an increased expression of IL-2 and IL-2-specific transcripts was detected. These data demonstrate that cytokine synthesis may be tightly controlled by redox-dependent processes. As thioredoxin is readily secreted and taken up by cells, it may play an important role as a costimulatory molecule involved in immune processes.
Modulation of endotoxin-induced histamine synthesis by cytokines in mouse bone marrow-derived macrophages.
Authors: Takamatsu S , Nakashima I , Nakano K 
Published: January 2023

Abstract
The aim of this study was to examine the roles of various cytokines in histamine synthesis by macrophages in bone marrow. Pure (&gt; 99% nonspecific esterase-, CD14-, and Mac-1-positive) macrophage populations were obtained after long term culture of bone marrow cells (bone marrow-derived macrophages). Culture of the cells in the presence of Escherichia coli LPS caused a slight, but dose-dependent, increase in histidine decarboxylase-associated histamine synthesis with a concomitant increase in the expression of CD14, a LPS receptor, as well as the Mac-1 Ag on their surface. Granulocyte/macrophage CSF (GM-CSF) or IL-3 strongly enhanced LPS-induced histamine formation and expression of CD14 on bone marrow-derived macrophages, without affecting the expression of Mac-1 Ag. GM-CSF and IL-3 also caused a marked accumulation of both histidine decarboxylase and IL-6 mRNAs in the cells. Macrophage CSF and IL-1-alpha also potentiated LPS-dependent histamine formation when it was stimulated with GM-CSF or IL-3. In contrast to these cytokines, IFN-gamma suppressed LPS-induced histamine production regardless of whether it was stimulated by GM-CSF or IL-3, and inhibited CD14 expression. Neither IL-6 nor granulocyte CSF had any appreciable effect on LPS-induced histamine production even in combination with GM-CSF or IL-3. These results suggest that GM-CSF and IL-3 enhance LPS-induced histamine production in bone marrow-derived macrophages and that macrophage CSF and IL-1 alpha augment the actions of GM-CSF and IL-3. Possible implication of CD14 molecule in the reactions is discussed.
T cells, but not thymic exposure to HLA-B27, are required for the inflammatory disease of HLA-B27 transgenic rats.
Authors: Breban M , Fernández-Sueiro J L , Richardson J A , Hadavand R R , Maika S D , Hammer R E , Taurog J D 
Published: January 2023

Abstract
Rats transgenic for the human MHC class I gene HLA-B27 are susceptible to a spontaneous multisystem inflammatory disease that resembles human B27-associated disease. This disease requires a high level of expression of the B27 transgene product in cells of hemopoietic origin and can be adoptively transferred to B27 transgenic or nontransgenic rats by transplantation of bone marrow (BM) or fetal liver (FL) cells. To investigate the role played by T cells and the thymus in the disease process, we produced congenitally athymic rnu/rnu F344 rats carrying the disease-prone B27 transgenic locus of the 33-3 line. Transgenic nude rats were protected from disease manifestations. This protection was abated by reconstitution with T cells from euthymic donors of the 33-3 line, with CD4 T cells being more efficient than CD8 T cells in transferring disease. Lethally irradiated, adult-thymectomized (ATX), nontransgenic recipients reconstituted with intact BM, T cell-depleted BM, FL, or nude BM from syngeneic disease-prone lines all developed disease. Pretreatment of the ATX nontransgenic recipients to deplete T cells enhanced the subsequent transferred disease. The inflammatory disease of B27 transgenic rats is thus T cell-dependent. The relevant T cells do not need to encounter B27 in the thymus, and residual radioresistant and/or extrathymically derived host T cells are sufficient to mediate the adoptively transferred disease. The data are most consistent with a model of B27-mediated disease arising from a failure of tolerance and requiring a population of CD4 T cells.
Self-reactive cytotoxic gamma delta T lymphocytes in Graves' disease specifically recognize thyroid epithelial cells.
Authors: Catálfamo M , Roura-Mir C , Sospedra M , Aparicio P , Costagliola S , Ludgate M , Pujol-Borrell R , Jaraquemada D 
Published: January 2023

Abstract
In this paper we report the isolation of a self-reactive cytotoxic gamma delta T cell line, 158RE.2, that originates from the T lymphocyte population infiltrating the thyroid gland of a patient with Graves' disease. Functional data using this cell line demonstrate that gamma delta T cells expanded in the thyroid tissue specifically recognize a ligand expressed by thyroid epithelial cells and cell lines of endocrine epithelial origin. The TCR expressed by these gamma delta T cells--V gamma I/V delta 5--is unusual in peripheral blood lymphocytes, and its specificity is clearly different from that observed in a high percentage of gamma delta T cells from PBL, which express the common TCR V gamma 9/V delta 2. The V gamma I/V delta 5 receptor is involved in the recognition of the ligand expressed by the thyroid cells, but not in the NK-like activity also displayed by 158RE.2. These cells express CD8 alpha alpha dimers, which participate in the thyroid ligand recognition but not in the NK-like activity. The epithelial cell recognition is not restricted by classical MHC class I or class II molecules, although the CD8 alpha alpha participation in the recognition suggests the involvement of nonclassical MHC molecules. These are the first data to be presented on self-reacting gamma delta T cells in human epithelium.
Glutamic acid decarboxylase autoantibodies in stiff-man syndrome and insulin-dependent diabetes mellitus exhibit similarities and differences in epitope recognition.
Authors: Daw K , Ujihara N , Atkinson M , Powers A C 
Published: January 2023

Abstract
Glutamic acid decarboxylase (GAD) is an autoantigen in two autoimmune diseases, insulin-dependent diabetes mellitus (IDDM) and stiff-man syndrome (SMS). However, most individuals with one of these diseases do not have the other disease. Prior studies have suggested that the natures of the GAD Abs associated with each of these diseases are different, which may have implications for the autoimmune pathogenesis. We have compared the GAD autoantibody profile and have mapped GAD protein epitope regions in the two diseases using an immunoprecipitation assay with recombinant GAD 65 and GAD 67 proteins, GAD protein fragments, and synthetic GAD peptides, as well as chimeric GAD proteins. Our results indicate that individuals with SMS have GAD Abs in 100- to 500-fold higher titer than individuals with IDDM. The population of GAD Abs in SMS sera is quite complex and includes those that recognize at least three GAD 65 epitope regions located between amino acids 1-16, 188-442, and 442-563. These types of GAD Abs are not found in IDDM sera. All SMS sera also had Ab specificity that binds GAD 67 in a region highly homologous to amino acids 188-442 of GAD 65. In contrast to prior studies that used immunoblotting to measure GAD Abs, we find GAD Abs in SMS sera also target two conformation-dependent regions of GAD 65, one located in the middle and one near the C-terminus of the protein. These two regions of the GAD 65 protein are similar to regions targeted by GAD 65-specific Abs found in individuals with IDDM. These results indicate that although disease-specific epitopes may exist, there is also overlap in the humoral response between the two diseases.
Class I-restricted presentation of an HIV-1 gp41 epitope containing an N-linked glycosylation site. Implications for the mechanism of processing of viral envelope proteins.
Authors: Ferris R L , Buck C , Hammond S A , Woods A S , Cotter R J , Takiguchi M , Igarashi Y , Ichikawa Y , Siliciano R F 
Published: January 2023

Abstract
Uncertainty exists over the site of processing of viral envelope (env) proteins for recognition by CTL. The extracellular domains of env proteins are not present in the cytosol, the site where the class I Ag processing pathway begins. Rather, the ecto-domains of env proteins are cotranslationally translocated into the endoplasmic reticulum during biosynthesis. To clarify the site of processing of viral env proteins, we examined the processing of an HLA B*3501-restricted epitope in the extracellular domain of the HIV-1 env protein. Although this epitope contains an N-linked glycosylation signal sequence, CTL specific for this epitope recognize a nonameric peptide that has not been previously modified by attachment of oligosaccharide. This was demonstrated in two ways. First, an env-specific B*3501-restricted CTL clone recognized a nonglycosylated, synthetic nonamer representing the minimal B*3501-restricted epitope, but not the glycosylated or deglycosylated forms. Second, the naturally processed, B*3501-restricted, env peptide is identical with a nonglycosylated, synthetic nonamer. Thus, the naturally processed form of an env epitope containing an N-linked glycosylation site is derived from env protein that is not glycosylated at the relevant asparagine during biosynthesis. Since the addition of N-linked oligosaccharides occurs only after the glycosylation signal sequence (N-X-S/T) is translocated into the endoplasmic reticulum, the initial processing reaction for this epitope may take place in the cytosol. Low-frequency failure of signal sequence containing polypeptides to engage the translocation apparatus, resulting in synthesis and degradation in the cytosol, may represent an important mechanism for the generation of class I-restricted CTL responses.
IL-10 cooperates with TNF-alpha to activate HIV-1 from latently and acutely infected cells of monocyte/macrophage lineage.
Authors: Finnegan A , Roebuck K A , Nakai B E , Gu D S , Rabbi M F , Song S , Landay A L 
Published: January 2023

Abstract
IL-10 is elevated in HIV-1-infected individuals and has been implicated in disease progression. In this study, we investigated the effects of IL-10 on the activation of HIV-1 from infected monocytes and macrophages. Although IL-10 alone did not induce HIV-1 replication, in the presence of TNF-alpha, IL-10 markedly enhanced virion production from a chronically infected promonocytic cell line (U1) and in acutely infected monocyte-derived macrophages. Neutralizing mAbs to IL-10 and TNF-alpha indicated that both cytokines were essential for the induction and were required to generate a synergistic increase in virus expression. The effects of the two cytokines were distinguishable functionally since pretreatment with TNF-alpha attenuated the cytokine cooperativity, while pretreatment with IL-10 potentiated their cooperativity, suggesting that IL-10 and TNF-alpha play different roles in the activation of virus. Northern blot analysis as well as Ab blocking and cytokine secretion studies indicated that the induction of either endogenous TNF-alpha or IL-10 was not involved in the cooperativity, nor was an up-regulation of TNF-alpha receptors. In combination with TNF-alpha, IL-10 stimulated activating protein-1 (AP-1) and nuclear factor (NF)-kappa B binding activities and cooperated to increase HIV-1 steady-state mRNA levels and enhance long terminal repeat-directed transcription through activation of the NF-kappa B binding sites, suggesting the IL-10 effect occurs at least in part at the transcriptional level. These results indicate that IL-10, in addition to down-regulating the cellular immune response to HIV-1, may also play a role in TNF-alpha-mediated activation of HIV-1 replication in the monocyte/macrophage lineage.
Antigen receptors on immature, but not mature, B and T cells are coupled to cytosolic phospholipase A2 activation: expression and activation of cytosolic phospholipase A2 correlate with lymphocyte maturation.
Authors: Gilbert J J , Stewart A , Courtney C A , Fleming M C , Reid P , Jackson C G , Wise A , Wakelam M J , Harnett M M 
Published: January 2023

Abstract
The Ag receptors on mature B and T cells are not coupled to the activation of cytosolic phospholipase A2 (cPLA2) and arachidonic acid release. Moreover, phorbol esters such as PMA, which can activate cPLA2 via mitogen-activated protein (MAP) kinase in most cell types, also failed to induce the release of arachidonate from mature cells, suggesting that the cPLA2 pathway may not be functional in mature lymphocytes. Interestingly, Western blot analysis revealed that cPLA2, which had previously been thought to be expressed ubiquitously, is not expressed in mature B or T cells and that cytosolic phospholipase A2 expression could not be up-regulated in lymphocytes following culture with a range of cytokines most likely to be involved in an immune response such as IL-1 alpha, IL-3, or TNF-alpha. In contrast, cPLA2 was shown to be expressed and activated in thymocytes and immature B cells under conditions in which ligation of the Ag receptors led to growth arrest and/or apoptosis. Taken together, these data suggest that cPLA2 does not play a role in Ag receptor-mediated lymphocyte activation, but may be involved in the molecular mechanisms underlying lymphocyte maturation and/or self tolerance by clonal deletion.
IL-10 inhibits nuclear factor-kappa B/Rel nuclear activity in CD3-stimulated human peripheral T lymphocytes.
Authors: Romano M F , Lamberti A , Petrella A , Bisogni R , Tassone P F , Formisano S , Venuta S , Turco M C 
Published: January 2023

Abstract
IL-10 markedly reduces nuclear factor (NF)-kappa B/Rel nuclear activity induced in PBMC by stimulation with the anti-CD3 mAb OKT3. The inhibition is exerted specifically on the NF-kappa B/Rel activation induced by mAb OKT3, and not that produced by PMA. As judged by supershifting the DNA-protein complexes with Abs recognizing specific components of the NF-kappa B/Rel protein family, the p50/p65 (Rel A) heterodimeric form of NF-kappa B is primarily affected. The maximal effect is observed at the IL-10 concentration of 20 U/ml. IL-10 inhibitory activity is exerted on T lymphocytes and is mediated by monocytes. Indeed, monocytes pretreated with IL-10 are able so inhibit NF-kappa B nuclear activity in purified T lymphocytes stimulated with OKT3. Soluble factors do not appear to be involved in the mechanism of inhibition. On the other hand, the up-regulation of CD80 Ag, found on monocytes obtained from PBMC incubated with OKT3, is not detected after addition of IL-10, and the anti-CD28 mAb CLB-CD28/1 restores the NF-kappa B/Rel nuclear activity in IL-10-inhibited lymphocytes. Therefore, the NF-kappa B/Rel inhibition might be ascribed to a lack of cooperation between accessory cells and T lymphocytes, resulting from down-regulation of a costimulatory molecule, such as CD80, produced by IL-10 on activated monocytes. Our results demonstrate that IL-10 can inhibit the induction of NF-kappa B/Rel nuclear activity in CD3-stimulated T lymphocytes. Since inappropriate activation of kappa B-driven genes has a physiopathologic role in a number of diseases, such as HIV infection, our findings support the possibility of using this cytokine to suppress an undesirable activation of these transcription factors.
Allele-specific motifs characterize HLA-DQ interactions with a diabetes-associated peptide derived from glutamic acid decarboxylase.
Authors: Kwok W W , Domeier M L , Raymond F C , Byers P , Nepom G T 
Published: January 2023

Abstract
Polymorphic residues of HLA class II molecules influence immune activation in part by determining specific structural constraints for binding antigenic peptides. We identified a peptide from glutamic acid decarboxylase, a diabetes-associated autoantigen that preferentially bound to HLA-DQ3.2 molecules, one of the HLA determinants highly associated with insulin-dependent diabetes. We analyzed interactions of specific HLA-DQ residues with modified peptide analogues and found a pattern of permissive site-specific amino acids that accommodated allele-specific binding. Four anchor residues constrain binding to different DQ alleles; limited variation at two of these sites, residues 4 and 9, accounts for the unique pattern of peptide binding to HLA-DQ3.1 or HLA-DQ3.2.
Specificities and functions of CD4+ HLA class II-restricted T cell clones against a human sarcoma: evidence for several recognized antigens.
Authors: Heike M , Schlaak J , Schulze-Bergkamen H , Heyl S , Herr W , Schmitt U , Schneider P M , Meyer zum Büschenfelde K H 
Published: January 2023

Abstract
CD4+ T cells play an important role for tumor immunity in animal tumor models, yet there are few reports about the role of CD4+ HLA class II-restricted T cells in the immune response against human tumors. Against a human sarcoma exclusively CD4+, T cell clones could be established. These T cell clones were cytotoxic and secreted TNF and additional cytokines in response to the IFN-gamma-treated, HLA class II-positive autologous sarcoma cells. Several Ags were recognized by representative T cell clones: an Ag presented by HLA-DR and specific for the sarcoma; Ags presented by both HLA-DR alleles of the sarcoma, HLA-DR4 and -15, and shared by allogenic HLA-DR matched cell lines of different tissue lineages, including B cell blasts; and a sarcoma Ag presented by HLA-DP or DQ. Cytokine profiles of sarcoma-reactive T cell clones were dependent on the cytokine environment present during establishment of the T cell clones. The addition of exogenous IL-4 shifted the cytokine patterns of sarcoma-reactive T cell clones from Th1-like patterns to Th0/Th2-like patterns and decreased IL-10 production. TNF, IFN-gamma, IL-4, and supernatants of T cell clones induced HLA-DR expression on the sarcoma cells and, thus, were able to enhance Ag presentation. This autologous T cell response to a human sarcoma represents a new model for HLA class II-restricted T cell responses to human tumors.
Response of a gamma delta+ T cell receptor invariant subset during bacterial infection.
Authors: Roark C E , Vollmer M K , Campbell P A , Born W K , O'Brien R L 
Published: January 2023

Abstract
Murine gamma delta T cells can be divided into subsets based on the TCR gamma-chains they express. Most of these subsets have variable TCR junctions, but two, both associated with epithelia, express invariant TCRs. The absence of receptor variability in these cells implies uniformity of their ligands. This was previously taken as evidence to suggest that gamma delta T cells recognize host-derived, stress-induced ligands. We now demonstrate, for the first time, the response of a gamma delta TCR invariant subset during bacterial infection, a potential cause of stress. After infection with Listeria monocytogenes, absolute numbers of all T cells in the liver, including alpha beta and gamma delta T cell subsets, increased markedly. However, responses of a gamma delta T cell subset varied. We noted a decrease in the relative frequency of V delta 6.3+ cells, which are, for the most part, included in the V gamma 1+ subset. In contrast, cells bearing the invariant V gamma 6/V delta 1 TCR increased substantially in proportion to other gamma delta T cells, as determined by PCR analysis of liver T cell RNA and by comparing liver gamma delta T cell hybridomas made from normal mice to those from mice infected with Listeria. V gamma 6/V delta 1+ cells have been previously reported as a TCR invariant intraepithelial subset in the female reproductive tract and tongue. We show here that V gamma 6/V delta 1+ cells reactive in Listeria-infected liver are polyclonally derived, but still bear TCR chains with invariant junctional sequences, identical with those of the female reproductive tract. Although the Ag that stimulates these cells is unknown, our results indicate that only diverse, but also invariant, gamma delta T cell subsets can become involved in the host response to a bacterial infection.