bluuebunny/crossref_metadata_2025_split huggingface dataset:
A fish oil diet rich in eicosapentaenoic acid reduces cyclooxygenase metabolites, and suppresses lupus in MRL-lpr mice.
Authors: Kelley V E , Ferretti A , Izui S , Strom T B 
Published: January 2023

Abstract
Dietary supplementation of fish oil as the exclusive source of lipid suppresses autoimmune lupus in MRL-lpr mice. This marine oil diet decreases the lymphoid hyperplasia regulated by the lpr gene, prevents an increase in macrophage surface Ia expression, reduces the formation of circulating retroviral gp70 immune complexes, delays the onset of renal disease, and prolongs survival. We show that a fatty acid component uniquely present in fish oil but not in vegetable oil decreases the quantity of dienoic prostaglandin E, thromboxane B, and prostacyclin normally synthesized by multiple tissues, including kidney, lung, and macrophages, and promotes the synthesis of small amounts of trienoic prostaglandin in autoimmune mice. We suggest that this change in endogenous cyclooxygenase metabolite synthesis directly suppresses immunologic and/or inflammatory mediators of murine lupus.
Nonphagocytic dendritic cells are effective accessory cells for anti-mycobacterial responses in vitro.
Authors: Kaye P M , Chain B M , Feldmann M 
Published: January 2023

Abstract
The accessory cell requirements for a given T cell response may be examined in vitro by using highly purified lymph node T cells. We have examined the capacity of different antigen-presenting cells to stimulate proliferation of Mycobacterium tuberculosis-primed T cells when the antigenic challenge is either soluble or particulate in nature. By titrations of cell number and antigen concentration, it was shown that dendritic cells are not only extremely efficient at presenting soluble mycobacterial antigen compared with various macrophage populations, but also that they are capable of presenting whole mycobacteria. Because phagocytosis of mycobacteria does not occur with these cells, we suggest that processing of antigen by dendritic cells may be initiated at the plasma membrane. Because macrophages are not essential for this in vitro response, a role for dendritic cells in antibacterial immunity in vivo is implicated.
Human mononuclear phagocyte antiprotozoal mechanisms: oxygen-dependent vs oxygen-independent activity against intracellular Toxoplasma gondii.
Authors: Murray H W , Rubin B Y , Carriero S M , Harris A M , Jaffee E A 
Published: January 2023

Abstract
To determine if the oxygen-dependent and -independent antiprotozoal mechanisms with which the human mononuclear phagocyte is equipped to act against Leishmania donovani operate against other intracellular parasites, oxidatively intact and deficient cells were challenged with Toxoplasma gondii. Fresh monocytes and lymphokine- or gamma-interferon (IFN-gamma)-activated macrophages from normal individuals killed 35% and 50% of T. gondii within 6 hr, respectively, and each of these cell populations inhibited the replication of surviving parasites 20 hr after infection. This activity was associated with the capacity to release large amounts of H2O2 (572 to 971 nmol/mg) and to respond to toxoplasma ingestion with respiratory burst activity. Impairing the ability to generate oxygen intermediates by glucose deprivation or treatment with superoxide dismutase, catalase, or mannitol inhibited toxoplasmacidal activity by greater than 80% and permitted a 2.6- to 4.3-fold increase in the number of intracellular toxoplasmas. In contrast to normal cells, fresh monocytes from patients with chronic granulomatous disease (CGD) killed less than 8% of toxoplasmas and exerted 50% less toxoplasmastatic activity. However, although associated with the induction of only modest toxoplasmacidal effects (18 to 20% killing), lymphokine stimulation did induce CGD monocytes and macrophages as well as oxidatively inactive human endothelial cells to display near normal levels of toxoplasmastatic activity. Similar to oxygen-dependent mechanisms, the enhancement of oxygen-independent activity by crude lymphokines could be abolished by a monoclonal anti-IFN-gamma antibody and could be achieved by treatment with recombinant IFN-gamma alone. Unstimulated CGD monocytes, however, were found to lose all antitoxoplasma activity after two days in culture, whereas normal cells continued to effectively inhibit T. gondii replication, suggesting that oxygen-independent responses may not actually be required for the normal monocyte to act against T. gondii. Taken together with previous findings with L. donovani, these results indicate that the human mononuclear phagocyte possesses an oxygen-independent antiprotozoal mechanism and that its effects can be enhanced by lymphokines (IFN-gamma), but that nevertheless this cell's primary response to intracellular protozoa is largely oxygen dependent.
The generation of major and minor idiotype-bearing families of anti-p-azophenylarsonate antibodies; stochastic utilization of VH gene segments.
Authors: Near R I , Manser T , Gefter M L 
Published: January 2023

Abstract
An average of 50% of anti-p-azophenylarsonate (Ars) antibodies bear a cross-reactive idiotype, IdCR, and an average of 15% bear a relatively minor idiotype, Id, in A/J mice. To begin to investigate the processes that influence the expressed levels of these idiotype-bearing antibodies in serum, we have examined the frequency among preimmune B cells of cells that utilize the heavy chain variable region gene segment (VH) needed for IdCR and that which is needed for Id anti-Ars antibody expression. Our results indicate these VH gene segments are functionally rearranged at frequencies one would expect for random usage. The frequency of VH gene segment utilization is similar to, if not higher than, that of VHCR, arguing that the predominance of IdCR-over Id-bearing antibodies is not due to preferential usage of the VHCR gene segment. In addition to the analysis of Ars-immune sera pooled from several mice, we have examined 20 individual A/J mice to determine whether the relative serum levels of IdCR- and Id-bearing antibodies are strictly regulated relative to each other. Among individuals, we find that IdCR and Id antibody levels fluctuate over a 28-fold and a 120-fold range, respectively. The ratio of IdCR to Id antibody levels was found not to be strictly regulated, varying over a 300-fold range. Linear regression analysis of IdCR relative to Id concentrations shows a correlation coefficient of only 0.093. Indeed, rare mice can be found that generate greater levels of Id-bearing antibodies than those bearing IdCR. These results are indicative of a stochastic process involved during the generation of these IdCR-and Id-bearing antibody families. Models accounting for the generation of this highly variable serologic response derived from a preimmune repertoire in which VH gene segments are equivalently utilized are discussed.
Human monocyte-mediated lysis of antibody-coated tumor cells: the role of the cytoskeleton in monocytes.
Authors: Espevik T 
Published: January 2023

Abstract
Human monocytes (M phi) show high cytolytic activity towards antibody-coated tumor cells (AbK562). In this report, the relationship between the cytoskeleton in the M phi and the M phi cytolytic activity has been investigated. The actin filament inhibitors cytochalasin B and dihydrocytochalasin B (H2CB) both reduced M phi-mediated lysis of AbK562 cells by approximately 50% at a concentration of 1 microM. This concentration of H2CB did not inhibit the number of target cells bound to M phi. Dihydrocytochalasin B did not inhibit the M phi ability to release cytotoxic protein factors, suggesting that H2CB does not inhibit lysis by inhibiting release of cytotoxic protein factors. Immunofluorescence microscopy showed a rapid accumulation of actin filaments towards the contact area in more than 80% of the examined M phi-AbK562 conjugates. Exposure to H2CB did not prevent this accumulation, but caused aggregation of the accumulated actin filaments in the contact area with the target cell. Accumulation of actin filaments did not occur toward tumor cells not coated with antibodies. Scanning and thin section electron microscopy demonstrated large M phi pseudopodia directed toward the AbK562 cells, with close apposition of the effector and target cell membranes with interdigitations. The formation of the M phi pseudopodia was inhibited by exposure to H2CB. These observations indicate that M phi membrane motility toward AbK562 cells is closely related to M phi-mediated lysis of AbK562 cells. Immunofluorescence microscopy of the microtubule-organizing center (MTOC) and the Golgi apparatus revealed that both the MTOC and the Golgi apparatus in M phi reoriented towards the bound AbK562 cells in approximately 45% of the examined M phi-AbK562 conjugates. The microtubule-depolymerizing drugs colchicine and vinblastine did not inhibit M phi-mediated lysis of AbK562 cells at concentrations which disrupted the microtubule arrays in the M phi. The carboxylic ionophore monensin, which blocks Golgi-derived secretion, inhibited M phi-mediated lysis of AbK562 to a lesser extent as compared to H2CB. These results suggest that microtubule functions are of less importance in M phi-mediated lysis of AbK562 cells as compared to actin filament functions. However, the MTOC and the Golgi apparatus could participate in M phi-mediated lysis of AbK562 cells by mechanisms related to secretion of cytotoxic molecules.
Cell surface comodulation of CD4 and T cell receptor by anti-CD4 monoclonal antibody.
Authors: Cole J A , McCarthy S A , Rees M A , Sharrow S O , Singer A 
Published: January 2023

Abstract
In our study we have used anti-CD4 mAb to investigate the cell surface association between CD4 and the Ag-specific TCR complex on mature peripheral T cells. Anti-CD4 mAb was administered in vivo and in vitro and its effects on CD4 and CD3 cell surface expression were determined. In vivo, anti-CD4 mAb reduced cell surface expression of its ligand, CD4, and secondarily also reduced cell surface expression of CD3/TCR on CD4+ splenic T cells. In vitro, multivalent cross-linking of CD4 by anti-CD4 mAb and either FcR+ cells or anti-Ig mAb also resulted in decreased surface expression of CD4 and specific comodulation of CD3/TCR. The secondary reduction in cell surface CD3/TCR expression induced by CD4 cross-linking could be pharmacologically disrupted by high doses of PMA, indicating that the comodulation of CD3 with CD4 was dependent upon intracellular mediators, possibly including protein kinase C. These results demonstrate that, in the presence of anti-CD4 mAb, CD4 is functionally associated with the CD3/TCR complex, and that this association is dependent upon the activity of intracellular mediators. Such intracellular mediators might induce the coordinate down-modulation of physically unassociated CD4 and CD3/TCR molecules, or, alternatively, might promote a physical interaction between CD4 and CD3/TCR molecules.
Murine natural suppressor cells in the newborn, in bone marrow, and after cyclophosphamide. Genetic variations and dependence on IFN-gamma.
Authors: Maier T , Holda J H , Claman H N 
Published: January 2023

Abstract
Natural suppressor (NS) cells are potent, Ag nonspecific, MHC-unrestricted inhibitors of immune responses. Murine NS activity is found in several situations, including adult bone marrow (BM) and neonatal/newborn spleen, and spleen following total lymphoid irradiation, after BM transplantation and after cyclophosphamide (CY) treatment. Using three of these situations (adult BM, newborn spleen, and spleen after CY treatment), the strain distribution of NS cell activity was assessed. A wide variation in potency is seen in both naturally occurring (adult BM and newborn spleen) and induced (after CY treatment) NS cell activity. Up to 10-fold differences in NS activity are seen between high and low NS strains. This reflects an intrinsic genetic variation between mouse strains in both naturally occurring and CY-induced NS cell activity. Thus, a strain with high NS activity at birth, has high NS activity in its BM as an adult and in its spleen after CY treatment. Of the strains tested, B10.D2 has the highest NS cell activity while BALB/c has the lowest, and the F1 between these two strains is intermediate in NS activity. Finally, the NS cell activity from all strains tested required IFN-gamma for expression of its inhibitory activity.
The Fc binding site for streptococcal protein G is in the C gamma 2-C gamma 3 interface region of IgG and is related to the sites that bind staphylococcal protein A and human rheumatoid factors.
Authors: Stone G C , Sjöbring U , Björck L , Sjöquist J , Barber C V , Nardella F A 
Published: January 2023

Abstract
The isolated 35 kDa fragment of protein G obtained by papain digestion of group G streptococci was found to bind solid phase intact IgG, Fc (2C gamma 2 + 2C gamma 3 domains), F(ab')2 and F(acb)2 (F(ab')2 + 2C gamma 2 domains) fragments but not pFc' (2C gamma 3 domains) fragments. The level of binding to rabbit F(acb)2 and rabbit F(ab')2 fragments was similar. Protein G binding to solid phase Fc fragments was inhibited by IgG, Fc, staphylococcal protein A and its monovalent fragment D, but was enhanced by F(ab')2 fragments. Chemical modification of tyrosine but not histidine residues of IgG abrogated its ability to inhibit the binding of protein G to solid phase Fc fragments. Protein G was found to strongly inhibit the binding of a monoclonal and a polyclonal human rheumatoid factor to IgG. These findings indicate that protein G binds with separate sites to the Fc and F(ab')2 fragments of IgG, that the interaction with the Fc fragment occurs at the C gamma 2-C gamma 3 domain interface region and that tyrosine but not histidine residues in this area are likely involved. The relationship of the Fc fragment-binding site specificity of protein G to that of other microbial IgG binding proteins and human rheumatoid factors is discussed.
The LFA-1 ligand ICAM-1 provides an important costimulatory signal for T cell receptor-mediated activation of resting T cells.
Authors: Van Seventer G A , Shimizu Y , Horgan K J , Shaw S 
Published: January 2023

Abstract
Functional studies demonstrate that T cell activation often requires not only occupancy of the TCR but costimulatory interactions of other molecules, which remain largely undefined. We have tested the hypothesis that LFA-1 interaction with its ligand intercellular adhesion molecule 1 (CD54) (ICAM-1) is such a costimulatory interaction in a model system using biochemically purified ICAM-1 and TCR cross-linking by anti-CD3 mAb OKT3 immobilized on plastic. Resting T cells do not respond to OKT3 mAb immobilized on plastic. However ICAM-1 deposited on plastic together with the nonmitogenic immobilized OKT3 results in a potent activating stimulus. This costimulation cannot be readily accounted for by ICAM-1-mediated adhesion but is consistent with a role in signaling, which is observed in ICAM-1-mediated augmentation of activation induced by PMA/ionomycin. The ability of ICAM-1 to costimulate with immobilized CD3 contrasts with minimal costimulatory activity of cytokines IL-1 beta, IL-2, and IL-6. The proliferative response to co-immobilized OKT3 and ICAM-1 is dependent on the IL-2R, which is induced only in the presence of both OKT3 and ICAM-1. The present data demonstrate that LFA-1/ICAM-1 interaction is a potent costimulus for TCR-mediated activation; this observation, interpreted in light of previous reports, suggests that LFA-1/ICAM-1 is of major physiologic importance as a costimulatory signal.
IL-1 activity is reduced in psoriatic skin. Decreased IL-1 alpha and increased nonfunctional IL-1 beta.
Authors: Cooper K D , Hammerberg C , Baadsgaard O , Elder J T , Chan L S , Sauder D N , Voorhees J J , Fisher G 
Published: January 2023

Abstract
IL-1 may influence or be influenced by a number of abnormalities present in psoriasis; including keratinocyte proliferation, eicosanoid production, fibroblast activation, endothelial cell adhesiveness, T cell infiltration and activation, cyclic nucleotide metabolism, and transmembrane signal transduction mechanisms. We assessed IL-1 regulation in normal, uninvolved, and involved skin of psoriatic patients using immunofluorescence microscopy, a sensitive ELISA method to quantitate immunoreactive IL-1 beta and IL-1 alpha protein levels, the thymocyte proliferation costimulation assay, costimulation of the LBRM.33 IL-1-sensitive cell line, and Northern blotting of cellular RNA to quantitate IL-1 alpha and beta mRNA. IL-1 beta was easily detectable by immunofluorescence microscopy and found to be localized predominantly in epidermal keratinocytes, whereas IL-1 alpha was not detectable with this method. Immunoreactive IL-1 beta was found to be elevated in cytosolic extracts derived from involved psoriatic keratomes relative to keratomes of normal skin. The elevated IL-1 beta protein was accompanied by elevated levels of IL-1 beta mRNA in psoriatic skin relative to normal skin. In contrast, immunoreactive IL-1 alpha levels were markedly reduced in lesional psoriatic skin. In functional assays using both the thymocyte proliferation assay and the LBRM.33 cell line, IL-1 activity from psoriatic involved skin keratomes was markedly reduced relative to that of uninvolved psoriatic keratomes and normal skin. All activity of both normal and psoriatic skin was attributable to IL-1 alpha. The elevated IL-1 beta immunoreactive protein present in psoriatic skin was found to be functionally inactive in these assays. The inactivity of the IL-1 beta was not due to an artifact of the cytosolic method of preparation because IL-1 beta released by psoriatic skin into the media was also nonfunctional. This was in keeping with the demonstration that the IL-1 beta was nonfunctional despite existing as a processed molecule. Taken together, these data demonstrate uncoordinated regulation of IL-1 alpha and Il-1 beta in psoriasis. The profound and complex changes in this system suggest IL-1 dysregulation may be integrally involved in the inflammatory, biochemical, and proliferative processes involved in the pathophysiology of psoriasis.
The expression of c-fos, c-jun, and c-myc genes is regulated by heat shock in human lymphoid cells.
Authors: Bukh A , Martinez-Valdez H , Freedman S J , Freedman M H , Cohen A 
Published: January 2023

Abstract
The effect of heat shock on the expression of the nuclear protooncogenes c-fos, c-jun, and c-myc was studied in human lymphoid cells. Heat shock caused an increase in c-fos and c-jun mRNA levels and a decrease in c-myc mRNA levels in pre-B (Hyon) and T (DND-41) cell lines as well as in freshly isolated normal human thymocytes. The changes in the mRNA levels of these protooncogenes in Hyon cells were most pronounced at 42 and 43 degrees C; kinetic analysis demonstrated that the changes could be detected within 30 min of heat shock. Altered transcription of c-fos and c-myc genes was the primary effect of heat shock. Secondarily, heat shock of Hyon cells stabilized the c-myc mRNA level by increasing its half-life from 24 to 45 min. The overall effect of heat shock on c-myc mRNA level, however, was a marked inhibition of its transcription. These results demonstrate that the transcription of nuclear protooncogenes is regulated by heat shock indicating a role for nuclear protooncogenes in the stress response of lymphoid cells.
Contributions of the CD2 and CD28 T lymphocyte activation pathways to the regulation of the expression of the colony-stimulating factor (CSF-1) gene.
Authors: Cerdan C , Razanajaona D , Martin Y , Courcoul M , Pavon C , Mawas C , Olive D , Birg F 
Published: January 2023

Abstract
The T cell adhesion molecule CD28 provides a costimulatory signal, in combination with either CD2 or CD3 mAb. CD28 appears to regulate the expression, by T cells, of cytokines normally produced by accessory cells, namely IL-1 alpha, TNF-alpha, and CSF-1. The CSF-1 gene is expressed as a 4.0-kb transcript by human T cells activated with mAb directed against CD2 and CD28, alone or in combination. A kinetic analysis of its expression showed low steady-state levels of the transcript after CD2 stimulation, and a transient rise after CD28 stimulation. In contrast, a mean fivefold increase in the levels of the transcript was detected in CD2 plus CD28-stimulated cells. The potential mechanisms regulating this increase were investigated. The half-life of the CSF-1 transcript was identical in cells activated with either CD28 or CD2 plus CD28. Transcription of the CSF-1 gene appeared to undergo attenuation in resting cells as well as in cells activated via a single pathway; this attenuation was relieved in part by the combined CD2 plus CD28 stimulation. Thus in vitro costimulation via the CD2 and CD28 molecules regulates the expression of the CSF-1 gene mainly at the transcriptional level.
Identification and distribution of the costimulatory receptor CD28 in the mouse.
Authors: Gross J A , Callas E , Allison J P 
Published: January 2023

Abstract
T cell activation requires Ag-specific stimulation mediated by the TCR as well as an additional stimulus provided by Ag presenting cells. On human T cells, it has been shown that antibodies to the Ag CD28 can provide a potent amplification signal for cytokine production and proliferation. Here we describe the production of a mAb to the murine homologue of CD28, and the use of this antibody to examine the function and distribution of CD28 in the mouse. Anti-murine CD28 synergizes with TCR-mediated signals to greatly enhance lymphokine production and proliferation of T cells, and the CD28 signal is not blocked by cyclosporin A. In the peripheral lymphoid organs and in the blood of the mouse, all CD4+ and CD8+ T cells express CD28. In the thymus, CD28 expression is highest on immature CD3-, CD8+ and CD4+8+ cells, and on CD4-8- cells that express alpha beta and tau delta TCR. The level of CD28 on mature CD4+ and CD8+ alpha beta TCR+ thymocytes is two- to fourfold lower than on the immature cells. The potent costimulatory function of CD28 on mature T cells, together with the high level of expression on CD4+8+ thymocytes, suggest that this costimulatory receptor might play an important role in T cell development and activation.
Lectin specificity and binding characteristics of human C-reactive protein.
Authors: Köttgen E , Hell B , Kage A , Tauber R 
Published: January 2023

Abstract
C-reactive protein (CRP) is thought to play an important role in immunomodulation. The exact biologic function of this pentraxin protein is, however, still unclear. Here we report experiments designed to further characterize the binding properties of CRP. Using purified human CRP it could be shown that CRP immobilized onto polystyrene surfaces or onto latex beads binds distinct plasma glycoproteins including IgG, asialofetuin, asialo-beta 2-glycoprotein I and, likewise, synthetic glycoproteins as a lectin, exhibiting binding specificity for terminal galactosyl residues of the glycoprotein glycans. Binding of CRP to IgA, IgM, IgG, asialofetuin, asialo-beta 2-glycoprotein I and to synthetic glycoproteins requires immobilization onto surfaces of both CRP and the ligand. Fibronectin and fibrinogen are bound by surface-immobilized CRP also in soluble phase. Comparing various mono-, di-, and trisaccharides as competitive inhibitors of the lectin binding activity of CRP, only beta-D-Gal-(1-3)-D-GalNAc, beta-D-Gal-(1-4)-D-GalNAc, and beta-D-Gal-(1-4)-beta-D-Gal-(1-4)-D-GlcNAc had significant inhibitory power at a concentration of 8 mmol/liter. Binding activity of CRP was pH-dependent with an optimum at pH 5 to 6 and was reduced by 90% when pH was shifted from 6 to the physiologic pH value of 7.4. CRP exhibited lectin-like properties with binding specificity for galactosyl residues also when bound to K-562 erythroleukemia cells. It is therefore suggested that CRP immobilized onto surfaces exhibits lectin activity toward galactosyl groups preferentially in a mildly acidic environment as present at sites of inflammation.