bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homogeneous antigen receptor beta-chain genes in cloned CD4- CD8- alpha beta T suppressor cells.
Authors: Schmidt-Wolf I G , Liang O , Dejbakhsh-Jones S , Wang H , Cheng L , Holm B , Bell R , Strober S 
Published: December 2022

Abstract
The rearrangements of beta-chain genes of the T cell Ag receptor were examined in 12 CD4- CD8- alpha beta + T cell lines derived from the spleen or thymus of neonatal or adult BALB/c mice. Eleven of the lines were cloned and established from six independent cloning procedures from different mice. Five cloned lines used V beta 9, four cloned lines used V beta 15, and two cloned lines used V beta 7. Nucleotide sequencing of the beta-chain genes showed that clones that used a given V beta were identically rearranged even when they were derived from independent cloning procedures. In the case of V beta 7 and V beta 15 all nucleotides in the V-D-J joining region were in the germ line configuration without N region additions. Rearrangements of the V beta 7, V beta 9, and V beta 15 genes were functional. Each V beta 15 clone also had a homogeneous rearrangement of the V beta 13 gene, which was nonfunctional. The predicted amino acid sequence of the joining regions of the V beta 7, V beta 9, and V beta 15 rearrangements showed homology in four of seven amino acids in the peptide contact region.
Binding of peptides lacking consensus anchor residue alters H-2Ld serologic recognition.
Authors: Solheim J C , Carreno B M , Smith J D , Gorka J , Myers N B , Wen Z , Martinko J M , Lee D R , Hansen T H 
Published: December 2022

Abstract
CTL recognize class I MHC/peptide complexes on the surface of target cells. Crystallographic and serologic data have indicated that peptide ligands can influence the conformation of class I molecules and hence T cell recognition. How the binding of peptides with disparate sequence motifs affects the conformation of distinct regions within a class I molecule remains unknown. A series of site-directed mutants of the murine class I molecule H-2Ld was studied to address this question. These mutants were generated by in vitro mutagenesis and used to map the serologic epitopes recognized by a panel of Ld-reactive mAb. The influence of six different ligands on serologic recognition by these mAb was then examined. Of 12 mAb tested, only one, B22/249, was found to be significantly influenced by the bound peptide. Peptide discrimination by B22/249 was observed at the cell surface and in immunoprecipitates of Ld after incubation with two of the six ligands. The two peptides that caused suboptimal B22/249 recognition of Ld/peptide lack a proline at position 2, which is present in the other four peptides and has previously been defined as an anchor residue for Ld ligands. The epitope on Ld detected by mAb B22/249 includes residues 63 to 70 on the alpha 1 domain helix. Two of these residues are in pocket B, which computer modeling predicts to be in contact with the second residue of Ld-binding peptides. Therefore, these data imply that a mAb to a class I molecule can distinguish peptides with different motifs, possibly reflecting peptide-dependent conformational changes in the class I molecule.
Effect of granulocyte/macrophage colony-stimulating factor on human monocytes infected with influenza A virus. Enhancement of virus replication, cytokine release, and cytotoxicity.
Authors: Bender A , Amann U , Jäger R , Nain M , Gemsa D 
Published: December 2022

Abstract
The activating properties of granulocyte/macrophage (GM)-CSF were studied in vitro with human monocytes infected by influenza A virus. When monocytes were pretreated for 8 h with GM-CSF (100 U/ml) and then exposed to influenza A virus, de novo virus protein synthesis was enhanced, more virus particles were released, and cells were killed at a higher rate. In virus-infected monocytes, GM-CSF induced a more rapid IFN-alpha release and potentiated production of TNF-alpha, IL-1 beta, and IL-6. Although GM-CSF or influenza A virus were each capable of independently activating TNF-alpha, IL-1 beta, and IL-6 gene transcription, a combination of both induced a massive cytokine mRNA accumulation which was readily translated into bioactive protein. Thus, GM-CSF may display a Janus-like action by accelerating virus infection but also by priming monocytes for elevated cytokine production. Whether the facilitated influenza A virus replication caused by GM-CSF may be counterbalanced by an improved cytokine response remains to be studied under more complex in vivo conditions.
70 kDa heat shock cognate protein is a transformation-associated antigen and a possible target for the host's anti-tumor immunity.
Authors: Tamura Y , Tsuboi N , Sato N , Kikuchi K 
Published: December 2022

Abstract
We previously investigated a novel heat-inducible transformation-associated cell surface Ag that is expressed on the activated H-ras oncogene-transformed rat fibrosarcoma W31, but not its parental nontransformed fibroblast WFB. This Ag was detected by mAb 067. Herein, we characterized the molecular nature of the Ag by using anti-heat shock protein (HSP) mAb. The accumulated data indicated that the cell surface expression of Ag was clearly enhanced by several stressors, such as TNF, L-azetidine-2-carboxylic acid, and sodium arsenite. The immunoprecipitate made with mAb 067 and W31 cell lysates reacted with anti-rat 70 kDa heat shock cognate (HSC) mAb, TG5E, indicating that 067-defined Ag may be a rat 70 kDa HSC. Because this Ag seemed to be one of the transformation-associated Ag of WFB, we further studied whether it could play an important role in the host's anti-tumor immunity. Peripheral T cells of rats primed with live BCG showed cytotoxicity to W31 but not to WFB. Because the possibility existed that HSP may interact with certain populations of T cells, we focused on the reactivity of CD4-CD8- double negative T (DNT) cells against 067-defined molecule. DNT cells from spleen and PBL of live BCG-primed rats showed the cytotoxicity against W31 cells. This cytotoxicity was completely blocked by mAb 067 and anti-CD3 mAb. However, it was not blocked by mAb R48B1 and 109, which detect the MHC class I nonpolymorphic determinant and a target molecule of the cytolysis by poly I:C-induced NK cells, respectively. Furthermore, brefeldin A was able to block the cytotoxicity against W31 targets by DNT cells, but not by NK cells. These data suggest that 70 kDa HSC may be a tumor Ag and may act as a presenting molecule perhaps complexed with cellular peptides to certain DNT cells.
Protein Fv produced during vital hepatitis is a novel activator of human basophils and mast cells.
Authors: Patella V , Bouvet J P , Marone G 
Published: December 2022

Abstract
Protein Fv is found in the normal liver and is released in the stools of patients suffering from viral hepatitis. Protein Fv isolated from five patients stimulated the release of histamine and sulfidopeptide leukotriene C4 from purified and unpurified peripheral blood basophils. Protein Fv absorbed with protein A-Sepharose coated with polyclonal IgG did not induce histamine secretion, whereas removal of putative contaminating Ig did not modify the releasing activity. The characteristics of the release reaction were similar to those of rabbit IgG anti-Fc fragment of human IgE (anti-IgE). There was an excellent correlation (Spearman rank coefficient (rs) = 0.83; p &lt; 0.001) between the maximal percent histamine release induced by protein Fv and that induced by anti-IgE from basophils. Preincubation of basophils with either protein Fv or anti-IgE resulted in complete cross-desensitization to a subsequent challenge with heterologous stimulus. Basophils from which IgE had been dissociated by brief exposure to lactic acid no longer released histamine in response to anti-IgE and protein Fv. A monoclonal IgE purified from a myeloma patient (patient ADZ) blocked both anti-IgE- and protein Fv-induced releases, whereas human polyclonal IgG and a monoclonal IgG purified from another myeloma patient (patient ZEG) selectively blocked protein Fv-induced secretion. Protein Fv also induced the release of preformed (histamine and tryptase) and de novo synthesized mediators (sulfidopeptide leukotriene C4 and/or PGD2) from mast cells purified from human lung parenchyma and skin tissues. There was a significant correlation between the maximal percent histamine release induced by protein Fv and anti-IgE from skin mast cells (rs = 0.63; p &lt; 0.01). There was also an excellent correlation between histamine and tryptase release caused by protein Fv from both lung (rs = 0.80; p &lt; 0.001) and skin mast cells (rs = 0.70; p &lt; 0.01). Thus, we established that protein Fv acts as a novel activator of human basophils and mast cells presumably by interacting with the VH domain of the IgE.
Age-associated changes in binding of human B lymphocytes to a VH3-restricted unconventional bacterial antigen.
Authors: Silverman G J , Sasano M , Wormsley S B 
Published: December 2022

Abstract
We have recently demonstrated that there is a site on Staphylococcal protein A (SpA) that interacts with B cell Ig receptors in a manner comparable with known T cell superantigens, because this binding specificity is restricted to Fab with VH3 H chains and most VH3 Ig bind SpA. In the present studies, SpA was used as a phenotypic marker for VH3 expression by human lymphoid cells. As expected, this Fab-mediated binding specificity was completely inhibited by certain VH3 antibodies but not by antibodies from other VH families. In multiparameter flow cytometric analyses, this binding activity was demonstrated to be highly prevalent among B cells (14 to 54%), and was more common among IgM-bearing B cells compared with IgG-bearing B cells. In all studies, Fab-mediated binding of SpA was uniformly expressed by a greater proportion of CD5-positive B cells than CD5-negative B cells. The proportion of B lymphocytes with this VH3-restricted binding capacity was found to undergo age-associated changes, because a large proportion of the peripheral B cells of neonates (mean +/- SD, 46.0 +/- 2.9%) bind this site, but two 10-mo-old subjects and older children had significantly lower binding levels (29.0 +/- 3.5%) that were the same as binding levels by adult peripheral B lymphocytes (30.2 +/- 3.3%). In immunohistochemical studies, tonsilar B cells that bind this site on SpA were shown to be common in mantle zones and germinal centers of secondary follicles. We speculate that Fab-mediated SpA binding represents a fundamental and primitive binding capacity that is part of the human preimmune repertoire, and we discuss the implications for the observed age-dependent shift in Fab-mediated binding of SpA by peripheral blood B cells.
Androgen-induced expression of the peripheral blood gamma delta T cell population in the chicken.
Authors: Arstila T P , Lassila O 
Published: December 2022

Abstract
Unlike alpha beta T cells, the physiologic significance of gamma delta T cells has remained elusive. In avian species they comprise a large circulating T cell subset. Here we report that in chicken around the time of sexual maturation (4 to 6 mo of age) a significant increase of the gamma delta T cells takes place in male but not in female chickens. The frequency of gamma delta T cells increases both in peripheral blood and spleen, but not in intestinal epithelium. This expansion is independent of MHC haplotype, being observed in various inbred and MHC-recombinant strains. Furthermore, administration of testosterone to young female chickens induces an equivalent increase in the frequency of gamma delta T cells in peripheral blood. These results indicate that sex, through androgens, has an effect on the gamma delta T cell numbers in a species, in which these cells form a major subset of peripheral lymphocytes.
Predominant role of tumor necrosis factor-alpha in human monocyte IL-10 synthesis.
Authors: Wanidworanun C , Strober W 
Published: December 2022

Abstract
In previous studies it has been shown that the bacterial endotoxin LPS induces an initial burst of inflammatory cytokine synthesis in human monocytes, which is followed by substantial IL-10 production; the IL-10 then down-regulates the inflammatory cytokine production as well as IL-10 production itself. Herein we tested the hypothesis that IL-10 production in human monocytes is under control of one of the cytokines induced by LPS. Accordingly, we cocultured purified human peripheral blood monocytes with a panel of cytokines including TNF-alpha, IL-1 alpha, IL-1 beta, IL-6, granulocyte macrophage-CSF, transforming growth factor-beta, and IFN-alpha and then measured IL-10 mRNA production using a semiquantitative reverse transcription-polymerase chain reaction technique. We found that TNF-alpha had a major effect on IL-10 mRNA production, inducing a 20- to 120-fold increase over baseline production. In contrast, IL-1 alpha, IL-1 beta, IL-6, granulocyte macrophage-CSF, transforming growth factor-beta, and IFN-alpha had little effect (&lt; 3-fold). The induction of IL-10 mRNA by TNF-alpha in monocytes was dose dependent and began between 8 and 24 h after the addition of TNF-alpha; this suggests that the increased IL-10 mRNA level was due to de novo mRNA synthesis rather than mRNA stabilization; this latter finding was corroborated by actinomycin-D time course studies, which showed that the half-life of IL-10 was less than 1 h and was not significantly altered by TNF-alpha. These studies concerning IL-10 mRNA induction by TNF-alpha were corroborated by studies of IL-10 protein secretion: TNF-alpha alone, but not IL-1 alpha, IL-1 beta, or IL-6 induces substantial IL-10 secretion. Furthermore, LPS induces a large amount of IL-10 secretion that is largely inhibited (50 to 75%) by anti-TNF-alpha but not by antibodies to other inflammatory cytokines. Finally, TNF-alpha augments LPS-induced IL-10 secretion. Taken together, these findings suggest that TNF-alpha is unique among the inflammatory cytokines in its role as an inducer of IL-10 in human monocytes, as such, it induces a molecule that provides negative feedback to its own production.
Class II MHC transcriptional mutants are defective in higher order complex formation.
Authors: Riley J L , Boss J M 
Published: December 2022

Abstract
Human class II MHC genes are regulated in part by a series of conserved upstream sequence elements termed the X1, X2, and Y boxes. Class II MHC transcriptional mutant B cell lines have been defined that differ with regard to the presence of RFX, an X1 box DNA-binding activity. To further characterize these mutant cell lines, we tested the ability of these conserved upstream elements to respond to the presence of known transcriptional activation domains. A series of HLA-DRA promoter reporter constructions carrying Gal4 binding sites and GAL4 fusion protein expression vectors were cotransfected into both wild type B cells and mutant B cells representing the two RFX phenotypes. Regardless of RFX or class II phenotype, the activation domains of GAL4-VP16 and GAL4-E1a could synergistically stimulate expression of constructions containing both the X2 and Y boxes. GAL4-VP16- and GAL4-E1a-mediated expression was inhibited by the presence of the X1 box in cells that contained RFX. In mutant cells that lacked RFX, GAL4-VP16 activation was not inhibited. In the RFX-positive class II mutant cell line RJ2.2.5, the X1 box inhibitory activity could be overcome by separating the Gal4 site from the X1 box by two additional helical turns, suggesting that the RFX factor is bound at the X1 site and sterically interferes with activation. This was not the case in wild type B cells, suggesting that a stable higher order complex forms in wild type cells and not in the mutant cells.
Granuloma eosinophils enhance IL-5 production by lymphocytes from mice infected with Schistosoma mansoni.
Authors: Metwali A , Elliott D , Blum A M , Weinstock J V 
Published: December 2022

Abstract
IL-5 is essential for granuloma eosinophilia in mice infection with schistosomiasis. The granulomas constitutively make IL-5 that originates from granuloma CD4+ T lymphocytes. This observation prompted us to learn whether non-T cell elements in the granuloma can promote constitutive IL-5 production. Neither granuloma eosinophils nor spleen cells from infected mice constitutively produced detectable levels of IL-5. Yet, mixing spleen cells with granuloma eosinophils resulted in spontaneous IL-5 secretion without promoting IL-4 production. Moreover, the admixed cultures were more responsive to anti-CD3 or soluble egg Ag than were cultures containing spleen cells alone. IL-5 ELISPOT assays in Transwell chambers showed that the cellular origin of IL-5 in the admixed cultures was the spleen cells, and that the phenomenon did not require cell-to-cell contact with granuloma eosinophils. Also, admixed cultures of granuloma eosinophils and spleen cells released less IL-5 in the presence of mAb that specifically blocked the biologic activity of either IL-2, IL-2R, or IAk. However, adding rIL-2 to spleen cell cultures at concentrations up to 100 U/ml could not stimulate secretion of IL-5. Because eosinophil supernatants contained no IL-2 as assessed by CTLL-2 bioassay, the release of IL-5 in response to eosinophils was not likely secondary to eosinophil secretion of IL-2. Thus, it appears that eosinophils produce a soluble substance that, with IL-2 and ongoing class II MHC/TCR interaction, enhances lymphocyte IL-5 output.
Mycobacteria-macrophage interactions. Macrophage phenotype determines the nonopsonic binding of Mycobacterium tuberculosis to murine macrophages.
Authors: Stokes R W , Haidl I D , Jefferies W A , Speert D P 
Published: December 2022

Abstract
During tuberculosis, host defenses may be determined, in part, by the capacity of resident, elicited, and activated macrophages to bind and ingest Mycobacterium tuberculosis. We have investigated the mechanism by which macrophages bind M. tuberculosis and other mycobacteria in a serum-free system. The extent of binding of M. tuberculosis to macrophages was dependent on the phenotype of the macrophage; thioglycollate-elicited and immune-activated macrophages bound mycobacteria poorly, whereas resident macrophages bound mycobacteria efficiently. Within 'freshly' explanted macrophage populations (from 2 to 24 h in vitro) poor binding of mycobacteria correlated with poor binding of C3bi-coated particles, but not with variations in the level of complement receptor 3 (CR3) expression. Induction of C3bi-coated particle binding in thioglycollate-elicited macrophages by PMA was not accompanied by enhanced M. tuberculosis binding. Inhibition of M. tuberculosis binding by resident macrophages could only be achieved using a mAb recognizing an epitope within CR3 distinct from that which recognizes C3bi. Our results suggest that nonopsonic binding of M. tuberculosis is mediated by a site within CR3, which is distinct from the C3bi binding site. In addition, we show a variation in the capacity of different macrophage phenotypes to bind mycobacteria nonopsonically. These data suggest that heterogeneity in macrophage-mediated clearance of M. tuberculosis may be a significant factor in the progression of tuberculosis.
Regulation of integrin-mediated myeloid cell adhesion to fibronectin: influence of disulfide reducing agents, divalent cations and phorbol ester.
Authors: Davis G E , Camarillo C W 
Published: December 2022

Abstract
Three different agents, dithiothreitol (DTT), Mn2+, and phorbol ester (TPA), were found to induce HL-60 cell adhesion to fibronectin through distinct mechanisms. The binding of HL-60 cells to fibronectin and a 120-kDa fibronectin fragment is completely dependent on the alpha 5 beta 1 integrin, the adhesion activators, and appropriate divalent cations such as Mg2+. Mn2+ alone was able to induce maximal adhesion in the absence of these other activators. With any of the three activators, Ca2+ inhibited adhesion to fibronectin substrates by inhibiting alpha 5 beta 1-fibronectin binding. DTT and Mn2+ were both found to enhance the binding of fibronectin to purified alpha 5 beta 1, which suggests that both agents can directly stimulate the integrin-ligand binding reaction. TPA acts by inducing intracellular phosphorylation whereas neither DTT nor Mn2+ induced protein phosphorylation. TPA-treated HL-60 cells adhere and spread on fibronectin substrates, whereas DTT- and Mn(2+)-treated cells adhere but do not spread. The actin cytoskeletal inhibitor, cytochalasin B, markedly blocks TPA-induced adhesion, has an intermediate effect on DTT-induced adhesion, and has a minimal effect on Mn(2+)-induced adhesion. Collectively, the data suggest that TPA seems to act by inducing phosphorylation events that lead to cytoskeletal changes and alpha 5 beta 1 integrin activation. In contrast, DTT and Mn2+ seem to act primarily by directly influencing the alpha 5 beta 1-fibronectin binding reaction. These studies characterize in detail a regulatory system for studying leukocyte alpha 5 beta 1-fibronectin adhesion and identify DTT as a novel activator of alpha 5 beta 1-fibronectin binding.
Modulation of murine macrophage function by IL-13.
Authors: Doherty T M , Kastelein R , Menon S , Andrade S , Coffman R L 
Published: December 2022

Abstract
Activated macrophages are important effector cells for immune response to many parasites and immune responses are strongly modulated in part by the effect of Th cell-derived cytokines on macrophages. Th1-derived cytokines such as IFN-gamma are strong stimulators of macrophage activation, while cytokines produced by Th2 cells, including IL-4 and IL-10, have been shown under some conditions to inhibit macrophage activities associated with inflammatory responses. IL-13, a recently described cytokine produced by Th2 cells, is also capable of down-modulating macrophage activity in a manner similar to that previously described for IL-4. Treatment of activated macrophages with IL-13 reduces the production of inflammatory monokines in response to IFN-gamma or LPS, both potent stimulators of these factors. In addition, IL-13 decreases the production of nitric oxide by activated macrophages. Nitric oxide has been implicated in both macrophage cytotoxicity and macrophage-associated immunosuppression. The suppression of nitric oxide by IL-13 leads to a decrease in parasiticidal activity by activated macrophages. However, our data indicate that IL-13 has pleiotropic effects, while the inflammatory potential of activated macrophages is significantly reduced, the potential of other macrophage subsets is unimpaired. These data indicate that IL-13 could be a potent modulator of immune responses in vivo, with effects that may embrace both macrophage suppressive and macrophage potentiating functions.
Nitric oxide signaling: a possible role for G proteins.
Authors: Lander H M , Sehajpal P K , Novogrodsky A 
Published: December 2022

Abstract
We have previously reported various inductive effects of nitric oxide on human PBMC. We describe a novel and potentially important mechanism of nitric oxide signaling-through direct activation of guanine nucleotide-binding proteins (G proteins). We have found that nitric oxide treatment of membranes isolated from fresh human PBMC enhances the ability of these membranes to hydrolyze [gamma-32P]GTP and bind [gamma-35S]GTP. In addition, treatment of whole cells with nitric oxide yielded membranes with enhanced GTPase activity. Furthermore, the GTPase activity of pure, recombinant Gs alpha, Gi alpha 1, and p21ras was greatly enhanced by nitric oxide. In support of the existence of this pathway in whole cells, we found that the G protein inhibitor, GDP-beta-S, blocked NF-kappa B translocation induced by nitric oxide or LPS in permeabilized cells. In addition, nitric oxide greatly reduced the pertussis toxin-mediated ADP-ribosylation of 45- and 41-kDa proteins in membranes of these cells. Because G proteins play a central role in many diverse signaling systems, activation by an endogenous and inducible oxidant may represent a novel signaling pathway.