bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dominance of resistance to the cytocidal effect of tumor necrosis factor in heterokaryons formed by fusion of resistant and sensitive cells.
Authors: Nophar Y , Holtmann H , Ber R , Wallach D 
Published: December 2022

Abstract
The mechanisms underlying differences in vulnerability to the cytocidal effect of TNF, among various cell lines and strains, were explored by examining the response to TNF of heterokaryons formed by fusing TNF-resistant and -sensitive cells. Several combination pairs of human and murine cells, differing significantly in response to TNF toxicity, yet expressing a similar level of TNF receptors, were examined. In all combinations tested, the heterokaryons exhibited resistance to TNF toxicity, comparable, in extent, to that of the more resistant of the two parental cell lines. This dominance of resistance suggests that differences in vulnerability to TNF toxicity reflect activities which are expressed by resistant cells and are deficient in vulnerable ones, activities which perhaps protect the cell against the cytocidal effect of TNF.
Modulation of human polymorphonuclear leukocyte IgG Fc receptors and Fc receptor-mediated functions by IFN-gamma and glucocorticoids.
Authors: Petroni K C , Shen L , Guyre P M 
Published: December 2022

Abstract
Human polymorphonuclear neutrophils (PMN) normally express two distinct types of IgG Fc gamma R, the 40-kDa Fc gamma R referred to as Fc gamma RII and the low affinity 50- to 70-kDa Fc gamma R designated Fc gamma RIII. A third type of Fc gamma R, the 72-kDa high affinity receptor known as Fc gamma RI, is also detectable on PMN that have been activated by IFN-gamma. Using mAb that discriminate among the three known types of Fc gamma R, we examined the effects of IFN-gamma and glucocorticoids on human PMN Fc gamma R expression. We also studied effects of IFN-gamma and the synthetic glucocorticoid dexamethasone (DEX) on antibody-dependent cytotoxicity (ADCC) of chicken erythrocytes and phagocytosis of IgG-coated ox RBC by human PMN. In 20 donors studied, we found that treatment of PMN with 400 U/ml IFN-gamma induced a 9- to 20-fold increase in the number of Fc gamma RI sites per cell, and DEX inhibited this induction of Fc gamma RI by 39 to 73%. Similarly, DEX significantly reduced the IFN-gamma stimulation of ADCC and phagocytosis. IFN-gamma had no effect on expression of Fc gamma RII or Fc gamma RIII. Fc gamma RI and Fc gamma RII expression was unaltered by 24 h of treatment with DEX alone, but Fc gamma RIII expression was sometimes increased by about 20% on PMN cultured with DEX. Nevertheless, we found a small but significant inhibition of ADCC and phagocytosis by 200 nM DEX. Our results indicate that Fc gamma RI plays a major but not exclusive role in the regulation of ADCC and phagocytosis by IFN-gamma and DEX.
Shared idiotypes on anti-DNA and anti-poly (ADP-ribose) antibodies.
Authors: Sibley J T , Latimer L J , Lee J S 
Published: December 2022

Abstract
Hed 10 is a ssDNA-specific mAb derived from an NZB/W autoimmune mouse. ADP 1 is a poly(ADP-ribose)-specific mAb derived from a C57BL/6 mouse. Rabbit anti-idiotypic sera were raised against Hed 10 and ADP 1. By affinity chromatography it was shown that at least 20 to 30% of DNA-binding antibodies contained these idiotypes. The sera were also used to evaluate idiotypic cross-reactivity among 26 diverse, predominantly anti-nucleic acid, murine mAb. Each serum bound directly to several mAb and in addition inhibited the binding of several antibodies to their appropriate Ag. The anti-Hed 10 serum detected an idiotype which was restricted to antibodies that bound to poly(dT) and/or poly(ADP-ribose). The anti-ADP 1 serum detected a more widely distributed idiotype contained in antibodies which bound to a variety of nucleic acids. Although both sera bound directly to Hed 10, only the anti-Hed 10 serum could compete for the binding of Hed 10 to poly(dT). On the other hand, both sera could compete for the binding of ADP 1 to poly(ADP-ribose) as well as bind directly to ADP 1. In addition anti-ADP 1 serum appeared to enhance, rather than inhibit, the binding of one mAb to native calf thymus DNA and poly[d(AT)] but had no effect on the binding to several ssDNA. These results demonstrate that many antibodies which recognize DNA and poly(ADP-ribose) have shared idiotypes. This may be of relevance to the development of autoimmunity because poly(ADP-ribose) is ubiquitous and immunogenic.
Studies of two antigenic forms of Ld with disparate beta 2-microglobulin (beta 2m) associations suggest that beta 2m facilitate the folding of the alpha 1 and alpha 2 domains during de novo synthesis.
Authors: Hansen T H , Myers N B , Lee D R 
Published: December 2022

Abstract
Sequential precipitation analysis of BALB/c Ag revealed two distinct antigenic forms of the Ld molecule distinguished by their reactivity with mAb 30-5-7. A similar analysis of Ag from the Ld transfectant T1.1.1 confirmed that both forms of Ld are products of the Ld gene. The 30-5-7+ form of Ld was found to be capable of association with beta-2 microglobulin (beta 2m) but could also exist as a free H chain, whereas the 30-5-7- form of Ld was incapable of beta 2m association. Unexpectedly, this latter form of Ld showed oligosaccharide maturation as well as cell surface expression, although less efficiently than the 30-5-7+ form of Ld. Pulse-chase experiments demonstrated that these two forms of Ld do not share a precursor-product relationship, but rather their distinguishing structures are fixed during de novo synthesis in the endoplasmic reticulum and remain constant throughout maturation and expression. Thus, beta 2m association is not an absolute requirement for intracellular transport and expression on the plasma membrane even in beta 2m+ cell types. Furthermore, in the context of other recent studies of Ld and Db, our results suggest that beta 2m plays a key role in folding the outer domains of class I molecules during de novo synthesis. It is speculated that beta 2m may provide a support structure analogous to a class II second domain, on which the class I binding site can be properly formed.
Pulmonary leukocytic responses are linked to the acquired immunity of mice vaccinated with irradiated cercariae of Schistosoma mansoni.
Authors: Aitken R , Coulson P S , Wilson R A 
Published: December 2022

Abstract
Pulmonary cellular responses in C57BL/6 mice exposed to Schistosoma mansoni have been investigated by sampling cells from the respiratory airways with bronchoalveolar lavage. Mice exposed to cercariae attenuated with 20 krad gamma-radiation developed stronger and more persistent pulmonary leukocytic responses than animals exposed to equal numbers of normal parasites. Although vaccination with irradiated cercariae also stimulated T cell responses of greater magnitude and duration than normal infection, the lymphocytic infiltrate elicited by each regimen did not differ substantially in its composition, 5 wk after exposure. Studies with cercariae attenuated by different treatments established that a link exists between the recruitment of leukocytes to the lungs of vaccinated mice and resistance to reinfection. There was a strong association between pulmonary leukocytic responses and the elimination of challenge infections by vaccinated mice. Animals exposed to irradiated cercariae of S. mansoni were resistant to homologous challenge infection but were not protected against Schistosoma margrebowiei. Homologous challenge of vaccinated mice stimulated anamnestic leukocytic and T lymphocytic responses in the lungs, 2 wk postinfection, but exposure of immunized animals to the heterologous species failed to trigger an expansion in these populations of cells. Our studies indicate that pulmonary leukocytes and T lymphocytes are intimately involved in the mechanism of vaccine-induced resistance to S. mansoni. It remains unclear whether these populations of cells initiate protective inflammatory reactions against challenge parasites in the lungs, or accumulate in response to the activation of the protective mechanism by other means.
Different induction patterns of mRNA for IFN-alpha and -beta in human mononuclear leukocytes after in vitro stimulation with herpes simplex virus-infected fibroblasts and Sendai virus.
Authors: Gobl A E , Funa K , Alm G V 
Published: December 2022

Abstract
Human peripheral blood mononuclear leukocytes (PBL) were stimulated in vitro by HSV type 1-infected glutaraldehyde-fixed fibroblasts, or Sendai virus (SV). The PBL containing mRNA for IFN-alpha 2 or -beta 1 were clearly identified by RNA-RNA in situ hybridization by using 35S-labeled alpha 2- and beta 1-probes. Although the two inducers gave similar levels of IFN in the culture medium (about 20 U/10(4) PBL), the patterns of expression of mRNA at the cellular level differed. The HSV induced only IFN-alpha mRNA in the PBL, with a lag of 1 to 2 h, and with a peak frequency of about 10 labeled cells/10(4) PBL at 6 h. Grain counts were high, the majority of cells having more than 50 grains. They were morphologically medium to large lymphocytes. The HSV-infected glutaraldehyde-fixed fibroblasts therefore induce IFN-alpha 2 mRNA in infrequent but highly efficient PBL, each cell capable of producing as much as 2 antiviral units of IFN-alpha. In contrast, SV induced both IFN-alpha 2 and -beta 1 mRNA in PBL, and without clear lags. IFN-beta 1 mRNA-positive PBL peaked somewhat earlier (4 h) than cells containing IFN-alpha 2 mRNA (6 h), and their mean frequencies were approximately 80 and 60/10(4) PBL, respectively, in a panel of PBL from six blood donors. Grain counts were lower than with the HSV inducer, the majority of cells having less than 50 grains, and most labeled cells were morphologically monocytes. The frequency of labeled PBL rapidly decreased with increasing culture time with both the SV and HSV inducers, was low at 12 h and almost absent at 24 h.
The human MHC-restricted cellular response to herpes simplex virus type 1 is mediated by CD4+, CD8- T cells and is restricted to the DR region of the MHC complex.
Authors: Schmid D S 
Published: December 2022

Abstract
The nature of the in vitro human cytotoxic T-cell responder population to HSV type 1 (HSV-1) was studied. In 5-day HSV-1-stimulated cultures that contained MHC-restricted activity, two phenotypically distinct populations of cells were present that were capable of lysing HSV-1-infected B cell lines in a 5-h 51Cr-release assay. The first was CD4+, CD8-, CD16- cell typical of class II-restricted T cells, whereas the other population bore a CD4-, CD8-, CD16+ NK-cell phenotype. Elimination of the NK cell fraction from bulk cultures by using anti-CD16 plus C frequently resulted in cell populations that killed in an Ag-specific, HLA-DR-restricted fashion. In some cases the anti-CD16-pretreated cultures retained a killing population that was unrestricted to MHC products. In no instance were any cytotoxic T cells that were restricted to class I Ag in evidence. Limiting dilution analysis of precursor frequency indicated that about 1 in 4000 to 1 in 8000 cells from peripheral blood are specific for HSV-1 in seropositive individuals. Comparisons of HLA class I-matched and HLA class II-matched targets with the autologous target by using limiting dilution analysis yielded results entirely consistent with those obtained in the bulk culture assay system.
T cell recognition of nonpolymorphic determinants on H-2 class I molecules.
Authors: Goldstein S A , Mescher M F 
Published: December 2022

Abstract
Recognition of polymorphic determinants on class I or class II MHC Ag is required for T lymphocyte responses. Using cell-size artificial membranes (pseudocytes) bearing H-2 class I Ag it is demonstrated that T cells can, in addition, recognize nonpolymorphic determinants on class I proteins. Pseudocytes bearing class I alloantigen stimulate in vitro generation of secondary allogeneic CTL responses. At a suboptimal alloantigen surface density, incorporation of class I molecules identical to those of the responder cells (self-H-2) or from third-party cells resulted in dramatically enhanced responses, whereas incorporation of class II proteins had no effect. The receptor that mediates recognition of conserved class I determinants has not been identified, but results of antibody blocking studies are consistent with the Lyt-2/3 complex of CTL having this role. Thus, class I proteins on Ag-bearing cells can have two distinct roles in T cell activation, one involving recognition of polymorphic determinants by the Ag-specific receptor and the other involving recognition of conserved determinants.
Protective, restorative, and therapeutic properties of recombinant human IL-1 in rodent models.
Authors: Castelli M P , Black P L , Schneider M , Pennington R , Abe F , Talmadge J E 
Published: December 2022

Abstract
Human rIL-1 alpha and -1 beta are shown to increase significantly the CFU-culture activity in the spleen as well as at other sites after i.v. or i.p. administration. IL-1 can also significantly increase survival and can "rescue" a number of animals if administered either before or after lethal doses of cyclophosphamide or gamma-irradiation. The protective and reconstitutive activities of the rIL-1 are shown to correlate with increased CFU-culture frequency and total number, as well as increased cellularity in the bone marrow and peripheral blood, suggesting that this is one of their mechanisms of action. The sequence and timing of administration of human rIL-1 is critical for the protection or rescue of animals receiving DNA-damaging agents; maximal activity is achieved when IL-1 is given 20 h before insult or 48 h after alkylating agent administration. Minimal therapeutic activity is observed with IL-1 as a single agent for the treatment of metastatic disease compared with other biologic response modifiers including IFN-gamma.
Further characterization of the membrane anchor found on the tissue-specific class I molecule Qa2.
Authors: Soloski M J , Lattimore A , Hereld D , Krakow J L , Low M G , Einhorn G 
Published: December 2022

Abstract
Previous studies have determined that various Qa2 serologic determinants can be removed from the surface of spleen cells by treatment with a phospholipase C. Our studies have determined that the class I molecule Qa2, expressed on the surface of spleen cells and activated T cells, behaves as an integral membrane protein based on its ability to associate with detergent micelles. Studies utilizing two purified phospholipase C have revealed that although most (90 to 95%) of the Qa2 molecules expressed on the surface of resting spleen cells are released as intact 40-kDa polypeptides associated with beta 2-microglobulin, activated T cells contain a major cell subpopulation expressing lipase-resistant Qa2 molecules. Flow cytometric analysis revealed that L3T4+-activated T cells expressed lipase-sensitive Qa2 molecules, whereas Lyt-2+ cells express lipase-resistant forms of the Qa2 molecule. The relationship between the secreted form of the Qa2 molecule and the lipase-generated soluble Qa2 molecule was investigated. Based on SDS-PAGE analysis, the secreted Qa2 molecules has a Mr of 39 kDa whereas the cell surface form released from either resting spleen or activated T cells by phosphatidylinositol-specific phospholipase C has a Mr of approximately equal to 40 kDa. Furthermore, the secreted Qa2 molecule lacks an epitope, cross-reacting determinant, often present on lipase-solubilized cell surface molecules. Thus, based on serologic and biochemical criteria, the soluble Qa2 molecules generated by an exogenous phospholipase C and the secreted Qa2 molecule are structurally distinct.
Activation of the alternative complement pathway by EBV and the viral envelope glycoprotein, gp350.
Authors: Mold C , Bradt B M , Nemerow G R , Cooper N R 
Published: December 2022

Abstract
The EBV-producing B lymphoblastoid cell line B95-8 was found to efficiently activate the alternative C pathway whether assessed with Mg-EGTA-treated human serum or with mixtures of the purified proteins of the pathway (PAP). The ability of the cells to activate was markedly increased after stimulation of EBV replication by treatment of the cells with a phorbol ester, and decreased by treatment of the cells with a viral polymerase inhibitor. Alternative pathway activation was dependent on the presence of either properdin or EBV-immune IgG; the addition of either alone to the PAP led to the deposition of 200,000 C3 molecules/cell. The addition of both properdin and immune IgG to the PAP markedly increased C3 binding to a level of 800,000 molecules/cell. Several lines of evidence indicate that the major external glycoprotein of EBV, gp350, mediates alternative pathway activation by B95-8 cells. First, the ability to activate C positively correlated with gp350 expression on the surface of the EBV-producing cells and gp350- cells failed to activate; second, the anti-EBV antibody in immune human sera which enhanced activation specifically immunoprecipitated gp350 from membranes of B95-8 cells; third, a significant proportion of the C3 which became bound to the cells during activation was attached either to gp350 or to the anti-gp350 antibody found in immune human sera; and fourth, purified gp350, as well as EBV, efficiently activated the alternative pathway. These results indicate that gp350, an EBV envelope glycoprotein, is an efficient alternative pathway activator and its expression on cell membranes is associated with the ability to activate C.
IgG subclass-associated affinity differences of specific antibodies in humans.
Authors: Persson M A , Brown S E , Steward M W , Hammarström L , Smith C I , Howard C R , Wahl M , Rynnel-Dagöö B , Lefranc G , Carbonara A O 
Published: December 2022

Abstract
Human IgG subclasses differ in their biologic functions and are restricted as specific antibodies to certain Ag. The basis for this restriction is unknown but in order to characterize it further, we obtained serum preparations containing one single subclass by using subclass-specific mAb in affinity chromatography. Subsequently we determined the affinity of antibodies in the four IgG subclasses for gp30/p25, a hepatitis B surface Ag (HBsAg) complex, for a nine-amino acid cyclical peptide representing residues 139 to 147 of HBsAg, and for a peptide representing residues 126 to 140 of the hepatitis B virus pre-S2 region and the relative avidity of IgG1 and IgG2 antibodies for purified pneumococcal polysaccharide type 3. Affinities to the HBsAg showed a clear pattern of decreasing affinity in the order IgG1 greater than IgG2 greater than IgG3 greater than IgG4 both in sera from vaccinated and from naturally infected individuals. The relative avidities of antibodies to the polysaccharide Ag had a reverse pattern, IgG2 greater than IgG1. In individuals with or without Ig H chain gene deletions where the anti-HBsAg response was restricted to one subclass, the affinity was similar to that observed for the same subclass in sera from individuals who in addition possessed high or low affinity antibodies of other subclasses.
Ig isotypes produced by EBV-transformed B cells as a function of age and tissue distribution.
Authors: Miyawaki T , Kubagawa H , Butler J L , Cooper M D 
Published: December 2022

Abstract
EBV can transform human B cells giving rise to lymphoblastoid cell lines that produce and secrete Ig. Herein B cells from various tissues of newborns and adults were transformed by EBV and their Ig products were analyzed with isotype-specific mAb. Although IgG- and IgA-bearing B cells were present in the newborn, EBV transformed IgM-producing cells almost exclusively in both newborn blood and breast milk. IgM-secreting cells were derived from IgM+ B cells and IgM- pre-B cells present in neonatal blood, but only from IgM+ cells in adult blood. Whereas in adults most EBV-transformed cells produced IgM, producers of IgG and of IgA were present in frequencies that varied according to the tissue source. Precursors of IgG-producing cells were relatively abundant in blood, spleen, and tonsil, and relatively infrequent in bone marrow and appendix. EBV-inducible IgA producers were relatively concentrated in the appendix and to a lesser extent in tonsils and blood. Differences in the subclass composition of EBV-transformed populations of IgG- and IgA-producers were also observed for the various adult lymphoid tissues. IgG1-producing cells predominated in most tissues, and precursors of IgG2 were largely confined to the circulation. Whereas IgA1-producing cells were predominant in all tissues, a marked enrichment in IgA2-producers was observed in the appendix. These results indicate a remarkable heterogeneity in the isotype distribution pattern of EBV-transformable B cells that is determined both by developmental age and tissue localization. We propose that EBV selectively transforms primed B cells, the isotype commitment of which varies according to tissue origin and age.
A novel natural inhibitor from Candida albicans hyphae causing dissociation of the neutrophil respiratory burst response to chemotactic peptides from other post-activation events.
Authors: Smail E H , Melnick D A , Ruggeri R , Diamond R D 
Published: December 2022

Abstract
Previous work established that Candida albicans hyphae release several inhibitors of human neutrophil function. We now report that the crude hyphal inhibitory product (CHIP) inhibits superoxide anion (O2-) production stimulated by FMLP in a dose-related manner with an EC50 of approximately 2 micrograms/ml. CHIP also inhibited O2- production stimulated by A23187 and by opsonized zymosan, although this effect could be overcome by increasing the concentration of agonist. No inhibition of the PMA-stimulated burst was seen at any concentration of PMA tested, indicating that CHIP neither affected polymorphonuclear neutrophil viability nor quenched superoxide anion detection. A saturating dose of inhibitor had no effect on chemotaxis stimulated either by 0.1 to 100 nM FMLP or by zymosan-activated serum. Peak inositol trisphosphate levels stimulated by FMLP were not inhibited by a dose of CHIP producing maximum inhibition of FMLP-induced superoxide production. Peak changes in cytosolic free calcium levels (as measured by indo-1 fluorescence) stimulated by 50 nM or greater FMLP were unaffected by CHIP, although for subsaturating doses of FMLP a more rapid decline from peak calcium levels was seen in CHIP-exposed cells. Taken together, these data suggest that the common fungal pathogen C. albicans releases a substance that selectively impairs the neutrophil respiratory burst. It appears to do so without inhibiting the fully assembled NADPH oxidase and with minimal or no effect on events tightly coupled to FMLP-R/G protein activation, suggesting that these events may be uncoupled from activation of the burst. In addition, the absence of effect of CHIP on chemotaxis despite profound inhibition of the respiratory burst suggests these neutrophil functions may be mediated by divergent transduction pathways.