bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of human neutrophils by substance P. Effect on oxidative metabolism, exocytosis, cytosolic Ca2+ concentration and inositol phosphate formation.
Authors: Serra M C , Bazzoni F , Della Bianca V , Greskowiak M , Rossi F 
Published: December 2022

Abstract
The neuropeptide substance P (SP), which has been suggested to mediate neurogenic inflammation, induces in human neutrophils the activation of the respiratory burst measured as O2 consumption and H2O2 production, and a cytochalasin B-dependent secretion of specific and azurophilic granules. The SP(4-11) fragment is much more stimulant than the entire molecule, whereas the SP(1-4) fragment is inactive. The respiratory and secretory response to SP are associated with an activation of phosphoinositide turnover, of Ca2+ influx and release from intracellular stores. Pertussis toxin inhibits 70% of the respiratory response and the residual 30% activity remains, even increasing 10-fold the concentration of the toxin. 1-(5-Isoquinolinesulfonyl)-2-methylpiperazine, a putative inhibitor of protein kinase C, does not modify the respiratory response to SP. Cytochalasin B significantly depresses the activation of the respiration by SP, whereas it moderately enhances the activation of phosphoinositide turnover and potentiates the increase of intracellular Ca2+ concentration. The results are discussed in relation to the receptor apparatus involved in SP activity, the signal transduction sequence activated by SP for the stimulation of NADPH oxidase, and the role of cell response to SP in the inflammatory process.
Identification of a T cell subset using a rabbit antibody raised against a T suppressor molecule.
Authors: North J , Weaver M S , Stammers A T , Chu N R , Chan A , Levy J G 
Published: December 2022

Abstract
Rabbit antiserum to a unique component of an Ag-binding Ts-factor was generated by repeated immunization with purified 30-kDa protein isolated from Fd11 Ts factor (11). This antiserum (anti-p30) was shown to recognize cell surface determinants expressed on the Ts hybridomas Fd11 and A10 but not the fusion partner BW5147. Furthermore, this antiserum was shown to bind to approximately 4% of thymocytes and 10% of nylon wool-purified splenic T cells from all strains of mice tested. Sorting nylon wool-purified T cells from DBA/2 mice for the CD4+ and CD8+ subsets revealed both populations contained cells that bound anti-p30. In addition, when CD4-8- thymocytes were examined for anti-p30 labeling, it was found that about 30% of this enriched population also expressed p30 molecules. In a functional study, anti-p30 was able to neutralize the suppressive effects of Fd11 on a specific assay for in vitro antibody synthesis against ferredoxin.
8-Mercaptoguanosine overcomes unresponsiveness of human neonatal B cells to polysaccharide antigens.
Authors: Rijkers G T , Dollekamp I , Zegers B J 
Published: December 2022

Abstract
We have shown previously that pneumococcal polysaccharides behave as human T cell-independent type 2 Ag. When cultured in vitro with type 4 pneumococcal polysaccharides (PS4), human neonatal B cells do not or only marginally respond. Limiting dilution analysis of neonatal B cells polyclonally activated by a combination of phorbol esters, calcium ionophore, and T cells and T cell factors, however, showed that Ag-reactive B cells are present in cord blood. The frequency of anti-PS4 reactive B cells in cord blood is comparable with that of adult peripheral blood. In order to obtain more insight into the activation requirements of these PS4-reactive neonatal B cells, 8-mercaptoguanosine (8MGuo) was added to in vitro cultures. Addition of 0.5 to 1.0 mM 8MGuo resulted in a 3- to 10-fold amplification of the anti-PS4 response. the effect of 8 MGuo was most prominent when added 3 days after initiation of the culture. Based on kinetic studies, we propose that in vitro activated cells are target for 8MGuo. These data further indicate that neonatal unresponsiveness to polysaccharide Ag is not due to the physical absence of Ag-reactive B cells but more likely to be the consequence of different activation requirements as compared with adult B cells.
Autoantibodies of primary biliary cirrhosis recognize dihydrolipoamide acetyltransferase and inhibit enzyme function.
Authors: Van de Water J , Fregeau D , Davis P , Ansari A , Danner D , Leung P , Coppel R , Gershwin M E 
Published: December 2022

Abstract
Autoantibodies against mitochondria occur in the sera of patients with primary biliary cirrhosis (PBC) with characteristic reactivity to an inner membrane protein of approximately 74 kDa. To precisely define these autoantigens, we recently cloned and sequenced a rat liver cDNA (pRMIT) that encodes for all of the epitopes recognized by Ig to the 74-kDa autoantigen. In the present study we have used this recombinant probe as a tool, in addition to purified enzymes, to demonstrate by immunoblotting that the 74-kDa mitochondrial autoantigen is dihydrolipoamide acetyltransferase (EC 2.3.1.12), the core protein of the pyruvate dehydrogenase complex. Furthermore, and of particular interest, inhibition of pyruvate dehydrogenase enzyme activity was demonstrated after incubation with sera from patients with PBC but not from normal volunteers or patients with chronic active hepatitis. Such inhibition was abrogated by absorption of the PBC sera with an expressing subclone of pRMIT, designated pRMIT-603. Identification of dihydrolipoamide acetyltransferase as the target of autoimmunity in PBC provides a reagent that can be used to determine mechanisms by which this molecule is recognized. It will allow study of whether autoimmune reactivity, at the humoral or T cell level, is the basis for the pathogenesis of PBC. Additionally, such data present evidence of functional inhibition of a critical metabolic enzyme. Dihydrolipoamide acetyltransferase is well-known to mitochondrial biochemistry and, similar to identified autoantigens in other autoimmune diseases, is highly conserved in evolution.
Structural basis for the C4d.1/C4d.2 serologic allotypes of murine complement component C4.
Authors: Taillon-Miller P A , Shreffler D C 
Published: December 2022

Abstract
The C4d.1 antigenic specificity was first defined serologically in 1959 as an H-2-associated cellular alloantigen first designated "G," later H-2.7. It was subsequently shown to be an allotype of component C4 of the C system, with the antigenic determinant carried on the C4d proteolytic fragment of the alpha-chain, thus the designation C4d.1. Alloantisera defining an antithetical Ag, C4d.2, were also prepared. Previous studies in our laboratory showed that the structural difference between the two specificities resides in a single tryptic peptide of C4d. As an efficient approach to definition of the amino acid difference(s) involved, genomic clones covering the C4d regions from two H-2 haplotypes of the C4d.1 type have been prepared and sequenced, and compared with two sequences already available for C4d.2-type molecules. The results indicate that the rather striking serologic difference between C4d.1 and C4d.2 is attributable to the single amino acid substitution of arginine in C4d.2 for glutamine in C4d.1. The substituted residue is in a highly hydrophilic region of the C4 molecule, at a position homologous to one that contributes to the Chido/Rodgers serologic difference of human C4 molecules. This substitution also determines a new Pst I site in C4d.1 strains. A HindIII restriction fragment length polymorphism between C4d.1 and C4d.2 has also been observed.
Transformation of prostaglandin D2 to isomeric prostaglandin F2 compounds by human eosinophils. A potential mast cell-eosinophil interaction.
Authors: Parsons W G , Roberts L J 
Published: December 2022

Abstract
PGD2 undergoes extensive isomerization in vivo followed by metabolism by 11-ketoreductase to yield a family of biologically active isomeric PGF2 compounds, including 9, alpha 11 beta-PGF2. Because immunologically activated human mast cells produce substantial quantities of PGD2 and eosinophils accumulate around mast cells at sites of immediate hypersensitivity reactions, the ability of eosinophils to metabolize PGD2 was investigated. Purified human circulating eosinophils from four different donors transformed PGD2 to 9, alpha 11 beta-PGF2 and 12-epi-9 alpha, 11 beta-PGF2 in a time- and concentration-dependent manner. The formation of these compounds increased rapidly during the first 30 min of incubation of eosinophils with PGD2 and tended to plateau at approximately 2 h. Detection and quantification of the formation of 9 beta,11 beta-PGF2 and its 12-epi isomer was accomplished by a negative ion chemical ionization gas chromatography/mass spectrometry assay. On one occasion, eosinophils from one donor also transformed PGD2 to two additional isomeric PGF2 compounds, the stereochemical structures of which were not identified. The ability of eosinophils to produce PGD2 was then investigated. After stimulation with 2 microM A23187, the major cyclooxygenase product formed was thromboxane B2 (2247 pg/10(6) eosinophils) whereas only small quantities of PGD2 were produced (50 pg/10(6) eosinophils). Inasmuch as PGF2 compounds can exert biologic actions that differ from those of PGD2, this ability of eosinophils to transform PGD2 to PGF2 compounds could alter the local biologic effects of PGD2 released from adjacent mast cells and thus may represent a physiologically relevant mast cell-eosinophil interaction.
Lack of cross-reactivity between variant T cell determinants from malaria circumsporozoite protein.
Authors: de la Cruz V F , Maloy W L , Miller L H , Lal A A , Good M F , McCutchan T F 
Published: December 2022

Abstract
The discovery of polymorphism in the T cell determinants of the protein that covers the surface of malaria sporozoites, the circumsporozoite protein (CSP), may have a negative effect on the course of development of a sporozoite-derived anti-malaria vaccine. Comparison of CSP gene sequences from Plasmodium falciparum suggests, based on the lack of silent (i.e., synonymous) substitutions, that polymorphism is being biologically selected for in the field. Thus, variation in T cell determinant sequences may actually be a means of immune evasion. The central question addressed here is whether or not the natural polymorphisms found in three identified T cell determinants in the CSP gene of P. falciparum are immunologically significant with regard to T cell stimulation. In support of the immune evasion hypothesis, we show here that animals immunized with peptides based on one sequence (i.e., the 7G8 isolate) will not significantly respond when challenged with variant peptides based on other CSP sequences (i.e., the LE5 and We1 isolates). Polymorphism in T cell determinants thus indicates that infection with sporozoites will not necessarily boost immune (antibody help and/or proliferative) responses stimulated by prior infections or by a particular vaccine construct based on these determinants. The implications of these findings in regard to vaccine development are discussed.
Molecular events during B lymphocyte differentiation. Induction of endogenous mouse mammary tumor proviral envelope transcripts after B cell stimulation.
Authors: Sharma S , King L B , Corley R B 
Published: December 2022

Abstract
We have identified a gene whose expression appears to be associated with a late stage in the differentiation of B lymphocytes into antibody secreting cells, as shown by using the inducible B cell lymphoma, CH12. Restriction mapping and partial sequencing of a cDNA clone isolated by subtraction analysis demonstrated that the clone, SC34, represents an envelope (env) gene transcript of a mouse mammary tumor virus (MMTV). In CH12 cells and in normal B cells, levels of MMTV RNA were increased after stimulation with LPS. The env transcript was the predominant MMTV RNA species and increased more dramatically than did levels of the genomic transcript. In differentiating CH12 cells, env transcripts increased as much as 20-fold above levels found in replicating, antibody nonsecreting CH12 cells. The major increase in expression appeared to be associated with B cell differentiation and not replication. By Southern blot analysis, only bands characteristic of endogenous proviruses were found in CH12, indicating that viral sequences were not amplified in this cell line. Restriction mapping indicated that the SC34 cDNA clone was a product of the Mtv-9 locus. Mtv-9 previously was shown to encode a complete MMTV provirus on chromosome 12, on which Ig heavy chain genes also are located. Increases in MMTV transcripts followed distinct kinetics and were quantitatively different from changes in immunoglobulin gene products. The expression of env RNA appears to more accurately reflect differentiation to antibody secretion in CH12 cells than does the expression of immunoglobulin gene transcripts.
Suppressor cell-inducing factor: a new lymphokine secreted by a natural suppressor cell line with natural cytotoxic activity. I. Purification to apparent homogeneity and initial characterization of suppressor cell-inducing factor.
Authors: Almawi W Y , Dolphin P J , Thies R L , McMaster W R , Levy J G , Pope B L 
Published: December 2022

Abstract
The lymphokine suppressor cell-inducing factor (SIF), obtained from 15 liters of serum-free culture supernatants of the natural suppressor cell line, M1-A5, has been purified to apparent homogeneity by a combination of gel filtration, ion exchange chromatography, and reverse-phase-HPLC. Purity of SIF was assessed by the migration of the factor as a single band on SDS-PAGE, and the elution from reverse-phase-HPLC column as a single and sharp peak. SIF activity was retained after both procedures. Two protein factors with SIF activity were isolated from M1-A5 culture supernatants. The first protein factor (SIF alpha) had a Mr of 43 kDa, and the second protein factor (SIF beta) had a Mr of 6 kDa. Final purification of SIF alpha yielded 5 micrograms protein with specific activity of 4 x 10(6) U/mg protein. Final purification of SIF beta yielded 40 micrograms protein with specific activity of 7.5 x 10(7) U/mg protein. The relationship between SIF alpha and SIF beta, as well as the relationship with other suppressor factors, will be addressed.
CR2 ligands modulate human B cell activation.
Authors: Bohnsack J F , Cooper N R 
Published: December 2022

Abstract
A considerable body of evidence from this and other laboratories indicates that complement receptor type 2 (CR2) modulates B cell activation and growth. In the present studies we have examined the effects of three different types of CR2 ligands, i.e., monomeric, aggregated, and latex-bound C3dg; mAb to different CR2 epitopes; and UV-inactivated, non-transforming EBV (EBVUV) for their actions on highly purified, high density resting tonsil B cells. Although none of these ligands induced B cells to enter the cell cycle or synergized with either anti-mu or low m.w. B cell growth factor in triggering B cell mitogenesis, aggregated C3dg, latex-bound C3dg, the OKB7 anti-CR2 mAb, and EBVUV-enhanced thymidine incorporation by phorbol ester-activated tonsil B cells. Such enhancement was not T cell or monocyte dependent. The major action of the CR2 ligands thus seems to be to enhance the transition of B cells activated by certain stimuli from the G1 to the S phase of the cell cycle. In contrast to the action of aggregated and latex-bound C3dg, monomeric C3dg was inhibitory for phorbol ester and aggregated C3dg-induced B cell activation. The HB-5 anti-CR2 mAb, which reacts with a different epitope on CR2 from that of OKB7, did not synergize with PMA in B cell activation. These data provide additional evidence for a role for the CR2 in the control of B cell growth and provide a useful model for studying the CR2-mediated signals that affect the growth of B cells.
In vivo restoration of T cell functions by human IL-1 beta or its 163-171 nonapeptide in immunodepressed mice.
Authors: Frasca D , Boraschi D , Baschieri S , Bossu P , Tagliabue A , Adorini L , Doria G 
Published: December 2022

Abstract
The immunorestorative capacities of human (hu) IL-1 beta or its synthetic fragment 163-171 (VQGEESNDK) were assessed in vivo in mice immunodepressed by aging, sublethal irradiation, or both. Subcutaneous administration of hu rIL-1 beta into immunodepressed animals immediately after carrier (horse red blood cells, HRBC) priming could restore to normal levels Th cell activity. This was measured as the ability of spleen cells from HRBC-primed mice to induce a hapten-specific antibody response in spleen cells from nonimmune mice in vitro stimulated with the hapten-carrier conjugate TNP-HRBC. In parallel, the ability of spleen cells from hu rIL-1 beta-treated immunodepressed animals to produce T cell growth factor activity upon in vitro mitogen stimulation was also increased significantly as compared to that of untreated mice and approached that of immunocompetent controls. The immunorestorative activity of hu rIL-1 beta on Th cell activity and T cell growth factor production could be mimicked by the synthetic nonapeptide 163-171 which, at the doses used, produced in most instances even greater effects than the whole protein. Although the optimal immunorestorative doses of the 163-171 peptide were several orders of magnitude higher than those of hu rIL-1 beta, the complete lack of IL-1-like inflammatory and toxic effects suggests that the synthetic hu IL-1 beta fragment may be successfully used as immunomodulating agent in the therapy of T cell immunodeficiencies.
Genetic restriction and fine specificity of human T cell clones reactive with rabies virus.
Authors: Celis E , Karr R W , Dietzschold B , Wunner W H , Koprowski H 
Published: December 2022

Abstract
Rabies virus-specific T cell clones isolated from a human vaccine recipient were studied for their fine specificity and genetic restriction using synthetic peptides of the viral Ag and mouse fibroblasts transfected with human MHC genes. Two clones were found to react with an epitope present in the rabies glycoprotein, which was presented by the HLA-DR7 molecule. Other T cell clones recognized synthetic epitopes corresponding to the rabies nucleoprotein in association with the HLA-DR7 or HLA-DQw3 molecule, and one clone responded to the viral nucleocapsid Ag in the presence of HLA-DPw4. T cell clones that exhibited different cross-reactivity patterns among several virus strains were found to recognize closely situated epitopes (within 15 amino acid residues), which were presented in the context of the same MHC molecule. The lack of recognition of a particular virus strain by a T cell clone was attributable in some cases to amino acid variations of the Ag that appear to affect the T cell's receptor for Ag specificity and not the ability of that epitope to associate with the corresponding MHC molecule. Comparisons of the T cell cross-reactivity patterns with various rabies and rabies-related viruses, the fine antigenic specificity, and MHC restriction may aid in understanding the role of individual amino acid variations among virus strains in the induction of cross-protective immunity.
Isolation of a cDNA encoding CD33, a differentiation antigen of myeloid progenitor cells.
Authors: Simmons D , Seed B 
Published: December 2022

Abstract
A cDNA clone encoding the human myeloid Ag CD33 was isolated from a U937 cDNA library after three rounds of transient expression in COS cells and enrichment by panning. COS cells transfected with the isolated clone expressed a surface protein recognized by the anti-CD33 mAb MY9, L1B2, and L4F3, having mass similar to but slightly smaller than the mass of CD33 expressed on myeloid cells. CD33 transcripts were found constitutively expressed in several myeloid progenitor cell lines. The cDNA sequence predicts a 40-kDa polypeptide with the typical features of a glycosylated integral membrane protein. The extracellular part of CD33 contains two Ig-like domains which are highly related to the first two domains of the neural cell myelin-associated glycoprotein and the B cell Ag CD22.
Obligatory role of IFN-gamma in induction of lymphokine-activated and T lymphocyte killer activity, but not in boosting of natural cytotoxicity.
Authors: Giovarelli M , Santoni A , Jemma C , Musso T , Giuffrida A M , Cavallo G , Landolfo S , Forni G 
Published: December 2022

Abstract
The biological role of the murine IFN-gamma endogenously secreted during cell activation has been probed by the use of a rat mAb (AN18) that specifically neutralizes its activity. When An18 mAb is added to the cultures of BALB/c and C57BL/6 nylon nonadherent spleen cells (naSpc) stimulated for 18 h with 1000 U of IL-2, the normally released IFN-gamma can no longer be detected in the supernatants and the IL-2-induced proliferative response is markedly reduced as compared with control cultures set up in the presence of an unrelated rat mAb. By contrast, the increased natural cytotoxicity is not affected. The 96-h culture of both BALB/c and C57BL/6 naSpc in the presence of 1000 U of IL-2 resulted in marked lymphocyte proliferation and generation of lymphokine-activated killer activity. The presence of An18 mAb strongly inhibited both functions. Similarly, when naSpc were stimulated with mitomycin C-inactivated allogeneic leukocytes in the presence of An18 mAb, the normal proliferative response and specific cytotoxicity were almost abolished, whereas the secretion of IL-2 was in no way affected. Lymphocytes recovered from 3-day cultures stimulated by IL-2 or allogeneic cells in the presence of An18 mAb displayed a decrease of the expression of the p55 chain of IL-2R, as shown by flow cytofluorimetry. Moreover, binding experiments with 125I-labeled IL-2 showed that lymphocytes from allostimulated cultures set up in the presence of An18 mAb display a decreased number of low affinity and almost no high affinity IL-2R as compared with control cultures. These data show that endogenous IFN-gamma plays an obligatory role for the de novo induction of cytolytic activity in lymphokine-activated killer cells and CTL, most probably by affecting the membrane expression of high affinity IL-2R.
Plasticity of T cell function. Cloned EL-4 lymphoma cells may help or suppress a primary antibody response depending on their own concentration and the assay system.
Authors: Melchers I , Rzepka R 
Published: December 2022

Abstract
Cloned EL-4 lymphoma T cells were tested in limiting dilution experiments for their capacity to suppress or to help the primary humoral immune response of spleen cells (or T cell-depleted spleen cells) to the Ag SRBC and 4-hydroxy-3-iodo-5-nitro-phenyl-keyhole limpet hemocyanin. EL-4 clones are able to suppress up to 80% of the total IgM responses in both systems, as well as to help. Suppression and help fluctuate between high and low levels with the numbers of EL-4 cells placed into tissue cultures. In Poisson plots, this is reflected as a "typical curve": usually one or two frequencies are estimated (e.g., integral of 1/4 and approximately 1/1000 for suppression and approximately 1/6 and approximately 1/200 for help), which appear regulated with increasing numbers of cells seeded. Control experiments showed that EL-4 cells need to be alive to exert the effects. EL-4 cells do not serve as additional antigen, do not induce an isotype switch and are not cytotoxic. Help and suppression are not restricted by the MHC. Help requires the presence of a small number of normal T cells in the assay system, indicating that EL-4 cells do not replace specific helper T cells. When a number of control cell lines were analyzed under identical circumstances, similar effects were observed with most long term T cell lines or clones expressing a T cell receptor, whereas cells of non-T lineages and T cells not expressing a T cell receptor did not show the phenomena. The results suggest a functional plasticity of T cells, dependent on cell numbers and the assay system used, and expressed via T cell communication.