bluuebunny/crossref_metadata_2025_split huggingface dataset:
Demonstration of NK cell-mediated lysis of varicella-zoster virus (VZV)-infected cells: characterization of the effector cells.
Authors: Tilden A B , Cauda R , Grossi C E , Balch C M , Lakeman A D , Whitley R J 
Published: December 2022

Abstract
Infection with varicella-zoster virus (VZV) rendered RAJI cells more susceptible to lysis by non-adherent blood lymphocytes. At an effector to target ratio of 80:1 the mean percentage of 51Cr release of VZV-infected RAJI cells was 41 +/- 12%, whereas that of uninfected RAJI cells was 15 +/- 6%. The increased susceptibility to lysis was associated with increased effector to target conjugate formation in immunofluorescence binding assays. The effector cells cytotoxic for VZV-infected RAJI cells were predominantly Leu-11a+ Leu-4- granular lymphocytes as demonstrated by fluorescence-activated cell sorting. The effector cell active against VZV-infected RAJI cells appeared similar to those active against herpes simplex virus (HSV)-infected cells, because in cold target competition experiments the lysis of 51Cr-labeled VZV-infected RAJI cells was efficiently inhibited by either unlabeled VZV-infected RAJI cells (mean 71% inhibition, 2:1 ratio unlabeled to labeled target) or HSV-infected RAJI cells (mean 69% inhibition) but not by uninfected RAJI cells (mean 10% inhibition). In contrast, competition experiments revealed donor heterogeneity in the overlap between effector cells for VZV- or HSV-infected RAJI vs K-562 cells.
Stimulation of B cells by sequential addition of anti-immunoglobulin antibody and cytochalasin.
Authors: Rothstein T L 
Published: December 2022

Abstract
B cells are stimulated to initiate DNA synthesis by modest doses of anti-immunoglobulin antibody in combination with cytochalasin. The ability of these agents to stimulate B cells in a sequential fashion was evaluated. Anti-immunoglobulin prepared cells to respond to subsequently added cytochalasin, but cytochalasin did not prepare cells to respond to anti-immunoglobulin. Only brief exposure to anti-immunoglobulin was needed to activate B cells for cytochalasin responsiveness; once activated, B cells remained responsive to cytochalasin for hours. The ability of cytochalasin to supply a second signal to activated B cells suggests that the cytoskeleton may be involved in generating or transducing growth-promoting signals for B lymphocytes.
Antibodies isolated by using cloned surface antigens recognize antigenically related components of Legionella pneumophila and other Legionella species.
Authors: Engleberg N C , Pearlman E , Dixon D , Eisenstein B I 
Published: December 2022

Abstract
We studied the antigenic cross-reactivity of surface proteins among various strains of Legionella pneumophila and other Legionella species by using a novel method of antibody purification. Anti-bacterial antibodies in hyperimmune sera were adsorbed to and eluted from the surface of recombinant E. coli cells that express individual L. pneumophila antigens on their surface. These affinity-purified antibodies were then used to probe protein immunoblots prepared from the test strains to detect cross-reactive domains. We found that antigenic proteins are generally conserved in all L. pneumophila serogroups. Although some of these antigenic domains are shared with members of other Legionella species, they are associated with proteins of different molecular mass. Our approach to the study of antigenic cross-reactivity has potential advantages over similar studies that use either monoclonal antibodies or monospecific antibodies prepared by immunization with purified antigens.
Production of T cell differentiation factor in syngeneic lymphocyte macrophage culture for cytotoxic T lymphocyte generation.
Authors: Ting C C , Hargrove M E , Loh N N 
Published: December 2022

Abstract
This study demonstrated that T cell differentiation factor (TCDF) was produced in syngeneic lymphocyte-macrophage cultures. Conditioned medium containing TCDF and interleukin 2 (IL 2) induced the differentiation of leukoagglutinin (LA)-activated cytotoxic T lymphocyte precursors (CTLp) into cytotoxic T lymphocyte (CTL) effectors. The production of TCDF and IL 2 peaked at day 4 to 5 in cultures containing normal spleen cells, syngeneic peritoneal macrophages, and indomethacin. Macrophages and T cells with Thy-1+, L3T4+, and Lyt-2- phenotype were needed for TCDF production. There was no requirement for xenogeneic serum in the culture medium; thus, TCDF could be produced in a syngeneic system. Recognition of self Ia molecules appeared to be essential for TCDF production, which was completely abolished by the addition of monoclonal anti-Ia antibody. In our experiments, removal of IL 2 from conditioned medium containing TCDF abolished its ability to generate LA-activated CTL. However, the cytotoxic response could be restored by the addition of a small amount (5 U/ml) of purified human recombinant IL 2 (HRIL 2), which alone was unable to generate LA-activated CTL at this dose. The generation of LA-activated CTL by high dose HRIL 2 (greater than 50 U/ml) was likely due to the endogenous production of TCDF. The bulk of TCDF could be separated from IL 2 by gel filtration in a Sephadex G-100 column. The peak of TCDF activity was concentrated at a m.w. of 16K dalton, and there was very little IL 2 activity in these fractions. When added alone to the LA-activated lymphocyte cultures, these active fractions were unable to induce CTL; supplementation of exogenous IL 2 was needed to restore the cytotoxic responses. Our findings indicate that both IL 2 and TCDF, which are needed in CTL generation. are produced in syngeneic cultures in the absence of antigenic or mitogenic stimulation.
Identification and recovery of Leishmania antigen displayed on the surface membrane of mouse peritoneal macrophages infected in vitro.
Authors: Williams K M , Sacci J B , Anthony R L 
Published: December 2022

Abstract
A murine monoclonal antibody (83L-2D3/a) to a dominant surface antigen of Leishmania braziliensis panamensis (WRAIR-470) recognized a determinant expressed on the surface membrane of mouse peritoneal macrophages infected in vitro. This determinant, also demonstrable on the surface membrane of intracellular amastigotes, was not displayed by the macrophage until at least 6 hr post-infection. This delay in expression and the obvious negativity of all uninfected macrophages inherent to infected cultures implied that the leishmania determinant had an intracellular origin. Furthermore, expression was dependent upon maintenance of macrophage function. When the parasite burden became overwhelming, additional antigen processing ceased, and that which had accumulated was either shed into the medium or was internalized. Immunochemical analyses revealed that the 83L-2D3/a reactive epitope was part of a 15,000 dalton molecule, which in all likelihood represents a breakdown product of a major surface glycoconjugate that had been degraded in the phagolysosome.
Cytotoxicity of monoclonal antibodies to a subset of Giardia isolates.
Authors: Nash T E , Aggarwal A 
Published: December 2022

Abstract
Previous studies showed that some Giardia lamblia isolates differ and can be categorized on the basis of their DNA banding patterns after digestion with endonuclease restriction enzymes, surface antigens, and excretory-secretory (E-S) products. In the present study, monoclonal antibodies (McAb) were produced that reacted with one specific group of Giardia isolates. These McAb recognized a 170,000 dalton antigen, which was present on the surface of these Giardia and released into the medium as an E-S antigen. This antigen was previously characterized and found to distinguish this subgroup of Giardia. In addition, these McAb were cytotoxic only for this subgroup of Giardia. Immobilization occurred immediately, and killing was documented by 7 min. The mechanism(s) of killing remains unknown but was shown to be complement independent and did not occur with Fab'. These McAb identifies certain isolates and can be used to type Giardia.
Complete nucleotide and derived amino acid sequences of sex-limited protein (Slp), nonfunctional isotype of the fourth component of mouse complement (C4).
Authors: Nonaka M , Nakayama K , Yeul Y D , Takahashi M 
Published: December 2022

Abstract
The nucleotide sequence coding for sex-limited protein (Slp), the testosterone-regulated isotype of the fourth component of mouse complement (C4), has been determined from cloned genomic DNA and cDNA fragments. The complete deduced amino acid sequence for the single chain precursor protein of Slp (pro-Slp) consists of 1716 residues. The mature beta, alpha, and gamma subunits contain 654, 763, and 291 amino acids, respectively. One potential carbohydrate attachment site is predicted from the beta-chain, five for the alpha-chain, and none for the gamma-chain. From the comparison with the mouse C4 sequences, an extensive overall sequence homology, 96.0% in nucleotides and 94.2% in amino acids, is observed. Only one deletion/insertion event is recognized between C4 and Slp sequences: three residues near the Cls cleavage site are deleted from Slp. The distribution of cysteine residues is completely conserved between pro-Slp and pro-C4.
Prophylactic treatment of BALB/c mice with cyclosporine A and its analog B-5-49 enhances resistance to Leishmania major.
Authors: Behforouz N C , Wenger C D , Mathison B A 
Published: December 2022

Abstract
The effect of cyclosporine A (Cs A) and its analog B-5-49 on Leishmania major in vitro and in vivo in the highly susceptible BALB/c mouse strain has been investigated. In vitro, both of these drugs showed significant toxicity toward L. major, but only at relatively high levels (greater than 25 micrograms/ml). However, at 5 and 10 micrograms/ml, levels which correspond more closely to physiologically achievable concentrations, no growth-inhibitory effect in vitro was observed. On administration of the drugs to animals with established lesions, no beneficial effect was observed and, in fact, some exacerbation of lesion development and disease progression was noted. Surprisingly, a majority of the mice treated prophylactically with Cs A for a period of 7 consecutive days beginning 1 day before infection with L. major did not develop ulcerated cutaneous lesions, although some footpad swelling was observed 10 days to 2 wk after infection. These resistant animals displayed a sustained DTH after infection, and were resistant to further challenge with virulent L. major. Prophylactic treatment with the B-5-49 analog of Cs A was also effective in enhancing resistance to L. major infection in BALB/c mice, although to a somewhat lesser degree. Because the cyclosporines tested do not appear to be directly toxic nor inhibitory in vivo for established L. major infections, it appears that these drugs may be effective in modulating the induction stage of the immune response toward the parasites in the BALB/c mouse in such a way as to allow a protective immunity to develop.
In vivo and in vitro expression of macrophage membrane interleukin 1 in response to soluble and particulate stimuli.
Authors: Kurt-Jones E A , Virgin H W , Unanue E R 
Published: December 2022

Abstract
We examined the expression of a membrane form of interleukin 1 (IL 1) by macrophages. Murine peritoneal macrophages fixed immediately after harvesting, in suspension, did not show membrane IL 1. Membrane IL 1 was expressed after a 3-hr culture on plastic dishes. These findings allowed us to examine some conditions in vivo that may trigger the expression of this protein; that is, by fixing the macrophages in suspension we could determine if a given stimulus had an effect. We found that membrane IL 1 was expressed briefly after administration of live or dead Listeria monocytogenes or endotoxin. Serum proteins were ineffective. At the time of maximal activation of macrophages by live Listeria, membrane IL 1 was not expressed. Analysis of in vitro conditions indicated that expression of membrane IL 1 and Ia molecules could be dissociated. In culture, recombinant interferon-gamma induced Ia but no membrane IL 1. Uptake of dead Listeria organisms had no effect on Ia but triggered membrane IL 1. The stimulation of membrane IL 1 was not caused by phagocytosis per se: latex particles were ineffective. Opsonized red cells stimulated membrane IL 1 on macrophages that were activated in vivo by inflammatory stimuli.
The role of nonactivated and interferon-gamma activated monocytes in regulating normal and SLE patient B cell responses to TNP-Brucella abortus.
Authors: Golding B , Tsokos G C , Fleisher T , Muchmore A V , Blaese R M 
Published: December 2022

Abstract
We have previously characterized the human B cell response to trinitrophenol (TNP)-Brucella abortus (Ba) response as being T cell independent. In this report we examine the role of monocytes in the TNP-Ba antibody response of human peripheral blood mononuclear cells (PBMC). Depletion of monocytes by sequential adherence to plastic and Sephadex G-10 passage did not result in decreased plaque-forming cell responses to TNP-Ba, suggesting that monocytes were not required. On the contrary monocytes were probably inhibitory because their removal resulted in enhanced responses. This was confirmed by showing that adding monocytes back reconstituted the inhibition. When interferon-gamma (IFN-gamma), a potent activator of monocytes, was added to TNP-Ba-driven PBMC cultures, marked inhibition (greater than 90%) of the responses ensued. This IFN-gamma-mediated suppression was monocyte dependent because it was completely abrogated by monocyte, but not T cell depletion. Previously, we described a concanavalin A (Con A), T cell inhibition pathway of the TNP-Ba response. Both the Con A and IFN-gamma pathways were tested for their ability to inhibit systemic lupus erythematosus (SLE) patient responses to TNP-Ba. The B cell response of SLE patients was inhibitable by both pathways. In all of the patients, the inhibition was complete (greater than 95%) when IFN-gamma was added to the cultures. In the presence of Con A, greater than 95% inhibition was observed in six of 10 patients, the remainder being inhibited to a lesser extent. Thus the hyperactive B cells from SLE patients can be down-regulated, particularly in the presence of IFN-gamma.
Effect of serotonin on murine macrophages: suppression of Ia expression by serotonin and its reversal by 5-HT2 serotonergic receptor antagonists.
Authors: Sternberg E M , Trial J , Parker C W 
Published: December 2022

Abstract
Serotonin (5-HT), a mediator released from platelets at sites of inflammation, suppressed IFN-gamma-induced Ia expression in mouse bone marrow macrophages maintained in vitro. (Mean percent suppression = 63.9% +/- 9.2, n = 40.) This suppression was not toxic or endotoxin-related, was concentration-dependent, and occurred at the physiologic concentrations of 5-HT present at inflammatory sites. The concentration of 5-HT producing the half-maximal effect was 2.5 to 5.5 X 10(-8) M. Related compounds, dopamine, histamine, and tryptamine, were much less potent in suppressing IFN-gamma-induced Ia, with maximally suppressing concentrations more than 100-fold higher than the maximally suppressing 5-HT concentration. L-5-hydroxytryptophan (5-HTP), the most potent analog tested, was 10-fold less potent than 5-HT in suppressing Ia expression. The concentration of 5-HTP producing the half-maximal effect = 4 X 10(-7) M. 5-HT suppression of IFN-gamma-induced Ia expression was antagonized by the 5-HT2 type receptor antagonists spiperone, ketanserin, and LY53857. Concentrations of these agents resulting in 50% inhibition of the serotonin effect were 1.5 X 10(-8) M, 7.5 X 10(-8) M, and 4.5 X 10(-12) M, respectively. 5-HT was most effective in suppressing IFN-gamma-induced Ia when added early in culture simultaneously with IFN-gamma. These data provide functional evidence that 5-HT suppression of IFN-gamma-induced Ia expression is mediated through a 5-HT receptor with some characteristics of the 5-HT2 type. 5-HT may play a physiologic role at sites of inflammation as a modulator of the effects of IFN-gamma on macrophage function.
In vitro activation of murine antigen-specific memory B cells by a T-dependent antigen.
Authors: Yefenof E , Sanders V M , Uhr J W , Vitetta E S 
Published: December 2022

Abstract
A procedure that generates an enriched population (60 to 85%) of memory B cells specific for TNP (TNP-MABC) was employed. The activation requirements of TNP-MABC for the T-dependent antigen TNP-KLH and carrier-primed helper T (Th) cells were compared to those for TNP-binding cells from nonimmune mice (TNP-ABC). Proliferation and differentiation of TNP-MABC in response to cognate recognition of antigen requires less antigen and fewer carrier-primed Th cells than the activation of TNP-ABC. Furthermore, responses of the TNP-MABC were of a greater magnitude. Non-cognate activation induces a low level of proliferation of both TNP-ABC and TNP-MABC, but induces differentiation of TNP-MABC only. Percoll density fractionation of spleen cells prior to enrichment for TNP-MABC suggests that the small, dense cell population responds to cognate, but not to non-cognate activation. FACS separation of TNP-MABC by surface Ig isotype reveals that approximately 80% of the secondary IgG response is derived from cells expressing sIgG. Such cells constitute less than 10% of the total number of TNP-MABC. Limiting dilution studies with sorted TNP-MABC indicate that sIgG+ TNP-MABC are enriched for precursors that give rise to a large clone size. The in vitro results indicate the existence of three putative pathways for antigen-specific memory B cell activation by a T-dependent antigen: 1) sIgG+ cells differentiating into IgG-secreting cells; 2) sIgM+ cells differentiating into IgG-secreting cells; and 3) sIgM+ cells differentiating into IgM-secreting cells.
Interferon-gamma suppresses B cell stimulation factor (BSF-1) induction of class II MHC determinants on B cells.
Authors: Mond J J , Carman J , Sarma C , Ohara J , Finkelman F D 
Published: December 2022

Abstract
The data presented in this manuscript extend our previous observations that recombinant interferon-gamma (reIFN-gamma) can suppress anti-immunoglobulin (anti-Ig)-stimulated B cell proliferation, and demonstrate that reIFN-gamma can also suppress B cell stimulation factor type 1 (BSF-1)-stimulated increases in expression of MHC class II molecules (Ia) on B cells. This suppression is most effective when relatively low concentrations of BSF-1 are employed, but is still very substantial even when optimal concentrations of BSF-1 were used. This suppression is also observed when size-separated small B cells which are devoid of detectable macrophages or NK cells are cultured with BSF-1 and reIFN-gamma, thus suggesting that IFN-gamma-mediated inhibition is a consequence of a direct effect on the B cells. Incubation of B cells with reIFN-gamma for 24 hr before their culture with BSF-1 did not prevent BSF-1-stimulated increases in sIa. This finding supports the contention that the effect of IFN-gamma is not mediated via the stimulation of "suppressor" influences in these cell cultures. The inhibition of B cell activation by IFN-gamma occurs within the first 3 hr after the onset of culture, as demonstrated by the inability of antibody to IFN-gamma to totally reverse the IFN-gamma-mediated suppressive effects on B cell proliferation if it is added later than 3 hr after the onset of culture. These results suggest a role for IFN-gamma in down-regulating the ability of B cells to function as antigen-presenting cells in non-cognate T cell-dependent responses.
Serologic aspects of IgG4 antibodies. II. IgG4 antibodies form small, nonprecipitating immune complexes due to functional monovalency.
Authors: van der Zee J S , van Swieten P , Aalberse R C 
Published: December 2022

Abstract
Human IgG4 antibodies directed against phospholipase A, the P1 antigen from Dermatophagoïdes pteronyssinus extracts, and cat albumin were found unable to cross-link antigen. Previously, it was demonstrated that IgG4 antibodies, in contrast to IgG1 antibodies, did not cross-link Sepharose-bound antigen and antigen added in solution. To eliminate the possibility that this phenomenon was caused by preferential binding of both IgG4 Fab fragments to the solid-phase-bound antigen, cross-linking of antigen was studied in a fluid-phase system. In this test, incapability of IgG4 antibodies to bridge two antigens was also found. As a result of such a phenomenon, it is expected that immune complexes formed by IgG4 antibodies will be considerably smaller than complexes formed by IgG1. This was confirmed by analysis of the molecular size profiles of IgG1- and IgG4-containing immune complexes in sucrose-density gradients. Moreover, IgG1 was able to precipitate antigen in a radioimmunoprecipitation test, whereas precipitation was not demonstrable by the same amount of IgG4 antibodies. Even 3% polyethylene glycol 8,000 did not precipitate the small IgG4-containing immune complexes efficiently. The antibodies studied were of a high-affinity type, and there was no significant difference in association constants between IgG1 and IgG4 antibodies. Therefore, we were not able to confirm observations reported in the literature that the IgG4 subclass is associated with a low-affinity antibody response; probably, the affinity of the IgG4 antibodies was underestimated by other investigators because of the polyethylene glycol precipitation technique used to separate antibody-bound and free antigen. Our findings stress the point that IgG4 antibodies take a special place in the immune response upon chronic exposure to antigen.
Macrophage-mediated fungistasis: requirement for a macromolecular component in serum.
Authors: Granger D L , Perfect J R , Durack D T 
Published: December 2022

Abstract
Peritoneal macrophages from Mycobacterium bovis- or Toxoplasma gondii-infected mice cultured in vitro in Dulbecco's medium containing 10% fetal bovine serum (FBS) and endotoxin stopped replication of Cryptococcus neoformans for 30 hr, whereas yeast cells cultured alone reproduced with a 3.0-hr doubling time. Without at least 5% FBS, macrophage fungistasis was poor. FBS without macrophages enhanced the growth rate of cryptococci. Macrophages preincubated in vitro for 24 hr without serum became fungistatic when challenged with cryptococci in medium with FBS but were not fungistatic without FBS. Macrophages preincubated in medium with FBS were never subsequently fungistatic. Dialyzed, heated (56 degrees C, 30 min), or delipidated FBS supported macrophage fungistasis, whereas FBS heated at 70 degrees C for 30 min did not. FBS contained no measurable opsonic activity for C. neoformans. Inclusion of endotoxin and/or murine IFN-gamma over wide concentration ranges did not substitute for FBS. Ultrafiltration estimation of FBS activity localized to 50 to 150 Kd. By gel filtration chromatography, FBS activity ran in the 25 to 100 Kd range. Dye-ligand affinity chromatography on Cibacron blue agarose gel dissociated the FBS activity from the albumin and lipoprotein fractions. Anion-exchange chromatography on DEAE-Sephacel revealed activity in the first fraction eluting at low ionic strength, pointing to a protein(s) with an isoelectric point toward neutral. Activated macrophages can prevent microbial replication within host tissues; the local environment is critical for fulfillment of this important physiologic function. These results point to a macromolecular factor(s) present in serum that is essential for full fungistatic capability of activated macrophages.