bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of metabolic inhibitors on spontaneous and interferon-boosted human natural killer cell activity.
Authors: Ortaldo J R , Phillips W , Wasserman K , Herberman R B 
Published: December 2022

Abstract
Human natural killer (NK) cell activity can be augmented by pretreatment with partially purified preparations of human interferon (IF). Studies have now been performed to determine the metabolic processes required for and involved in spontaneous NK activity and augmentation of cytotoxicity. A 4-hr 51Cr release cellular cytotoxicity assay was used to measure the NK activity, and peripheral blood leukocyte cells (PBL) were treated with: a) x-ray or mitomycin C; b) actinomycin D; or c) emetine, cycloheximide, pactamyhcin, or puromycin to assess the roles of DNA, RNA, and protein synthesis, respectively, in spontaneous NK activity and in boosting by IF. Prolonged incubation (18 hr) of PBL after blockage of synthesis of DNA almost completely abrogated NK activity; however, NK activity could be partially or totally restored to these populations by incubation of the effector cells for 1 hr at 37 degrees C with IF. Blockage of DNA synthesis for 1 hr had no effect on spontaneous NK activity or on boosting by IF. Inhibition of RNA synthesis also had no effect on spontaneous NK activity. Treatment of PBL with actinomycin before exposure to IF prevented boosting, but treatment with the RNA synthesis inhibitor after boosting with IF for 5 to 6 hr no longer had an appreciable effect on cytotoxicity. The effect of protein synthesis inhibitors on spontaneous NK activity was dependent on the inhibitor selected. Emetine and puromycin totally abrogated spontaneous NK activity at concentrations of inhibitor that blocked 3H-leucine incorporation 90% or more. In contrast, cycloheximide and pactamycin had only minimal effects on spontaneous NK activity but totally abrogated the boosting of IF.
Mutual recognition of parental and F1 lymphocytes. II. Analysis of graft-vs-host-induced suppressor cell activity for T cell-mediated lympholysis to trinitrophenyl self and alloantigens.
Authors: Polisson R P , Shearer G M 
Published: December 2022

Abstract
Spleen cells from (C57BL/10 x B10.A)F1 mice that had been injected 2 wk earlier with C57BL/10 (B10) or B10.A parental spleen cells were mixed with spleen cells from untreated F1 mice. The cell mixture was sensitized in vitro to trinitrophenyl-modified syngeneic cells (TNP-self) or alloantigens for a cell-mediated lympholysis (CML) response, and assayed for effector cell activity 5 days later. Cells from B10.A- but not B10-injected F1 spleens suppressed the CML of normal F1 spleens cells. In contrast, strong suppressive activity was obtained from irradiated B10-injected F1 mice. Thus, F1 mice were selectively resistant to GVH-associated immunosuppression induced by B10, but not by B10.A, parental spleen cells, and this F1 resistance mechanism appeared to be radiosensitive. The suppressive activity of spleen cells from irradiated, parental-injected F1 mice could be at least partially accounted for by cytotoxic activity of parental cells directed against alloantigens expressed by the F1. However, suppressor activity in intact parental-injected F1 mice appeared to be due to parental-induced F1 suppressor cells. The results are discussed with respect to: a) the use of this system as a possible model for investigating the selective resistance of F1 mice to parental T cell-induced GVH reactions, and b) the implications involved in the mutual recognition between F1 and parental lymphocytes, which may be relevant for immune surveillance against self-reactive T cell clones.
HLA-DRw alloantigens can be detected on peripheral blood T lymphocytes.
Authors: Mann D L , Sharrow S O 
Published: December 2022

Abstract
Antisera detecting HLA-DRw antigens (human Ia-like) react in cytotoxicity assays with peripheral blood B cells and monocytes but not T lymphocytes. Antisera detecting DRw specificities were used in flow microfluorometry studies to determine whether T lymphocytes express these antigens in quantities not detected by cytotoxicity. Peripheral blood lymphocytes depleted of monocytes were incubated with DRw antisera, reacted with fluoresceinated goat anti-human IgG, and analyzed on the fluorescence-activated cell sorter (FACS). Anti-DRw sera were found to be reactive on all of the lymphocytes as evidenced by a positive fluorescence signal. The reactivity was specific in that only those sera that detected DRw antigens on B cells and monocytes were reactive with the total lymphocyte population from the same donor. Reactivity of the antisera was removed by absorbing the antiserum with monocyte/B cells and T cells from a donor with the same DRw antigen as that found on the target cell of the donor tested. The results demonstrate the presence of DRw antigens on resting peripheral blood T lymphocytes. The implications of quantitative differences in DRw antigen expression on lymphoid cells are discussed.
Relative resistance of the F-42-stabilized classical pathway C3 convertase to inactivation by C4-binding protein.
Authors: Daha M R , van Es L A 
Published: December 2022

Abstract
The sera of some patients with SLE contain an IgG antibody (F-42) directed against the classical pathway C3 convertase (C-42), which is capable of stabilizing C42 in a dose-dependent manner. The half-life (T 1/2) of C42 is prolonged by F-42. In order to determine whether C4-binding protein was capable of reversing stabilization of C42, stabilized and unstabilized cell-bound C42 were exposed to purified C4-bp and the convertase activity was assessed. C4-bp was capable of accelerating the decay of C42 in a dose-dependent manner; 2 microgram/ml C4-bp reduced the T 1/2 of C42 from 5 to 2.5 min at 30 degrees C. On the other hand, 16 microgram C4-bp could reverse stabilization of C42 by F-42 from T 1/2 = 78 min to a T 1/2 - 40 min; 128 microgram C4-bp reduced the T 1/2 of stabilized C42 to 4 min. Functional inactivation of C42 occurs via enhanced decay-dissociation of C2 from the convertase by C4-bp, as shown by the release of 125I-C2i from the cell-bound convertase. Stabilization of C42 by F-42 is caused by prevention of decay-dissociation of 125I-C2. F-42 was also capable of stabilizing C4oxy2 even further, as shown by prolongation of the T 1/2 of cell-bound C4 oxy2 to a T 1/2 of at least 300 min at 30 degrees C.
Regulation of lymphocyte responses by human gangliosides. I. Characteristics of inhibitory effects and the induction of impaired activation.
Authors: Whisler R L , Yates A J 
Published: December 2022

Abstract
Gangliosides obtained from normal human brain were found to inhibit the in vitro activation of human lymphocytes by nonspecific mitogens and allogeneic cells at concentrations between 3 to 50 microgram/1.5 to 1.7 X 10(5) lymphocytes/0.2 ml culture. Ganglioside inhibition did not represent cytotoxic effects or altered lectin binding and was independent of the mitogen concentration. In addition to concentration, the degree of inhibition was dependent on the mode of presentation to lymphocytes, since gangliosides incorporated within liposomal membranes displayed a synergistic inhibitory effect greater than predicted from the cultures receiving either gangliosides or liposomes alone. In binding experiments, radiolabeled ganglioside GM1 became associated with human lymphocytes within 10 min. However, approximately 72 hr pre-exposure of human lymphocytes to gangliosides was required to induce impaired lymphocyte responses to mitogens and allogeneic cells. Thus, concentrations of human gangliosides equivalent to the levels occurring in the sera of patients with certain malignancies are capable of actively inhibiting lymphocyte stimulation in addition to inducing impaired lymphocyte responses.
Regulatory role of IgE-binding factors from rat T lymphocytes. IV. Formation of IgE-binding factors in rats treated with complete Freund's adjuvant.
Authors: Hirashima M , Yodoi J , Ishizaka K 
Published: December 2022

Abstract
Mesenteric lymph node (MLN) cells from rats treated with complete Freund's adjuvant (CFA) spontaneously released soluble factors, which have affinity for IgE (IgE-binding factors). The factors were purified by absorption of culture filtrates of the lymphocytes with IgE-Sepharose followed by elution at acid pH. Purified IgE-binding factors selectively suppressed IgE-forming cell response of DNP-ovalbumin-primed MLN cells to homologous antigen without affecting the IgG2 response. Fractionation of purified IgE-binding factors on lentil lectin-Sepharose showed that the majority of IgE-binding factors did not have affinity for lentil lectin, whereas a minor fraction was bound to the lectin-coupled beads. It was found that IgE-binding factors lacking affinity for lentil lectin suppressed IgE response, whereas those eluted from lentil lectin-Sepharose selectively enhanced IgE response. Serum of CFA-treated animals also contained both IgE-suppressive factor and IgE-potentiating factor, and the amount of the former factor was more than the latter. The source of IgE-suppressive factor is non-B lymphocytes. Depletion of Fc, receptor(+) lymphocytes in MLN cells from CFA-treated animals did not affect the formation of IgE-suppressive factor, indicating that Fc epsilon R-bearing cells are not the source of the factor.
Mechanism of lethal effect of human serum upon Leishmania donovani.
Authors: Pearson R D , Steigbigel R T 
Published: December 2022

Abstract
In order to gain greater understanding of potential host defense mechanisms against Leishmania donovani, we examined the effect of nonimmune, human serum upon promastigotes and amastigotes. Fresh sera were found to be lethal for promastigotes, but had no detectable effect on amastigotes. Serum exposed promastigotes became immotile, did not take up neutral red dye, appeared to be disrupted, and failed to recover after further incubation in fresh media. Heat labile components were required for promastigote killing since heat-inactivated serum (56 degrees C, 30 min) agglutinated but did not kill them. Sera that lacked either the 5th or 6th complement (C) component had no effect when used alone, but when used together, were lethal, indicating that activation of the membrane attack complex (C5b-C9) ws necessary for the lethal effect. The mode of C activation was determined by using serum with complete, selective, deficiency of C2, and normal serum chelated with Mg-EGTA. The C2-deficient serum killed promastigotes only after the addition of purified C2, and Mg-EGTA chelated serum had no detectable lethal effect. Thus, promastigotes appeared to activate C through the classical pathway. Human IgG and IgM, detected with 125I-anti-human antibody, bound to promastigotes. Removal of antibody from serum by absorption with promastigotes eliminated the lethal effect. The effect was restored by addition of heat-inactivated serum to absorbed serum. We conclude that promastigotes bind antibody and are killed by activation of the membrane attack complex of C through the classical pathway.
Lymphocyte activation by purified carrageenan.
Authors: Ishizaka S , Hasuma T , Otani S , Morisawa S 
Published: December 2022

Abstract
The induction of polyclonal antibody production and mitogenic response by purified carrageenan was studied in vitro by using spleen cells. It was shown that kappa-CGN, lambda-CGN, and iota-CGN induced significant responses in mice, hamsters, and rats. The less purified CGN also exhibited the polyclonal antibody production in mice. In addition, purified CGN exhibited mitogenic action on B cells and to a lesser extent, on thymocytes. Polyclonal antibody responses induced by purified CGN were not affected by removal of T cells, adherent cells, or iron powder phagocytic cells. These results suggest that CGN may activate B cells resulting in polyclonal antibody responses.
Inherited deficiency of the ninth component of complement in man.
Authors: Lint T F , Zeitz H J , Gewurz H 
Published: December 2022

Abstract
A 76-year-old man was found to have low (33% normal) serum complement (C) hemolytic activity, although C3 and C4 protein levels were normal. Further evaluation of his serum and plasma indicated that all C components were present in normal or elevated amounts except for C9, which was undetectable by both antigenic and functional assays. Addition of purified human C9 led to full restoration of the hemolytic activity. Family studies demonstrated that the deficiency was inherited as an autosomal codominant trait and was not linked with alleles at the HLA-A or HLA-B loci. The patient had no history of recurrent or unusual infections and no evidence of autoimmune disease. The availability of serum totally lacking in C9 permitted an investigation of the lytic capacity of the C5b-8 segment of the C attack mechanism, which was pursued in kinetic studies on the hemolysis of erythrocyte intermediates. These studies indicated that hemolysis occurred approximately 100 times slower in patient than in normal serum, using either EA or EAC1-7 intermediates as target cells. Serum bactericidal activity also was slower in patient serum, occurring at a rate about 1/35 that observed in normal serum. These studies provide direct independent evidence that cytolysis of erythrocytes and bacteria can be mediated by C5b-8, and allow a quantitative estimation of the increment in the rates of these reactions provided by normal serum levels of C9. The presence of readily detectable though slow hemolytic activity of C9-deficient serum may account for the difficulty in identifying individuals with this defect.
The role of agonists that activate adenylate cyclase in the control of cAMP metabolism and enzyme release by human polymorphonuclear leukocytes.
Authors: Marone G , Thomas L L , Lichtenstein L M 
Published: December 2022

Abstract
An inverse relationship between cAMP content and effector function is ascribed generally to immune and inflammatory cells. Previous reports imply, however, that human polymorphonuclear leukocytes (PMN) are less responsive than other inflammatory cells to adenylate cyclase (AC) agonists. We therefore examined the effects of isoproterenol, prostaglandin E1 (PGE1), adenosine, and histamine on the adenosine 3',5'-monophosphate (cAMP) content of PMN and on particle-stimulated lysosomal enzyme release. For comparison, the effect of AC agonists on the cAMP content of human peripheral lymphocytes was evaluated in parallel. Although potent stimuli for cAMP accumulation in lymphocytes, the AC agonists produced only marginal increases in the cAMP content of PMN; this difference in responsiveness was independent of agonist concentration or length of incubation. Inhibition of lysosomal enzyme release by the AC agonists was likewise marginal (&lt; 20%). The addition of theophylline with isoproterenol produced additive inhibition without significant cAMP increases. Hydrocortisone, which caused a small increase in the cAMP content, markedly potentiated the effects of AC agonists on the cAMP level in PMN; the synergistic increases in cAMP were accompanied by additive effects on lysosomal enzyme release. It is concluded that human lymphocytes and PMN exhibit differential sensitivity to AC agonists and that this difference may provide a basis for the selective modulation of individual PMN- or lymphocyte-mediated events.
Differentiation of human B cells expressing the IgA subclasses as demonstrated by monoclonal hybridoma antibodies.
Authors: Conley M E , Kearney J F , Lawton A R , Cooper M D 
Published: December 2022

Abstract
Monoclonal hybridoma antibodies to the human IgA subclasses were produced by immunizing mice with purified myeloma proteins. These antibodies were shown to be specific for the appropriate IgA subclass by enzyme-linked immunoabsorbant assay (ELISA) and by immunofluorescent staining of myeloma plasma cells and B cells from normal individuals. These antibodies were used to demonstrate age-related shifts in the proportions of IgA1- and IgA2-bearing B cells that could be correlated with 3 distinct staining patterns. In the newborn equal numbers of IgA1 and IgA2, B cells were found. These cells had only small amounts of surface IgA in a patchy distribution. They also expressed surface IgM. In the infant, large lymphoblastoid cells were observed that bore more IgA in a homogeneous pattern but did not express IgM. Of these cells, 98% were positive for IgA1. In the adult, 80% of the IgA B cells were positive for surface IgA1, and 20% were positive for IgA2. These were small lymphocytes brightly stained for IgA and negative for IgM. In culture, the adult B cells responding to pokeweed gave rise to roughly equal numbers of IgA1 and IgA2 plasma cells. These results suggest that there are equal numbers of precursor cells for IgA1 and IgA2 whose expansion, further differentiation, and migration are selectively affected by immunoregulatory controls.
Differences in the regulation of humoral responses between mice infected with Trypanosoma cruzi and mice administered T. cruzi-induced suppressor substance.
Authors: Cunningham D S , Benavides G R , Kuhn R E 
Published: December 2022

Abstract
In the present study, the effects of Trypanosoma cruzi and the T. cruzi-induced serum suppressor substance (SSS) on antibody responses were compared. Although infection with T. cruzi led to an alteration in T cell helper activity and a reduced specific B cell precursor frequency, SSS did not have a similar effect on either of these cell populations. The characteristics of the altered T cell helper activity was further investigated, and it was found that helper activity appeared earlier in infected mice than in normal or SSS-suppressed mice, and less antigen was required for optimal elicitation of T helper cells in infected mice. The potency of T cell helper activity also was shown to differ, and in the order T. cruzi-infected 6E normal 6E SSS-suppressed mice. It was found that spleen cells from T. cruzi-infected mice elaborated more potent specific helper factors than spleen cells from normal or SSS-suppressed mice, but did not produce a detectable nonspecific helper factor in vitro. Finally, the addition of B cells from low-dose primed, T. cruzi-infected mice to cultures of normal spleen cells resulted in subnormal responses to the priming antigen (sheep erythrocytes) but not to another unrelated antigen (trinitrophenyl-haptenated Brucella abortus), whereas similarly sensitized B cells from normal or SSS-suppressed mice caused no such effect.
Clonal nature of the immune response to phosphocholine. IX. Heterogeneity among antibodies bearing M511 idiotypic determinants.
Authors: Wolfe J , Claflin J L 
Published: December 2022

Abstract
A fraction of serum anti-PC antibodies from mice immunized with PC-KLH expresses idiotypic determinants of the PC-binding myeloma MOPC-511. We examined the molecular heterogeneity of IgG antibodies bearing the M511 idiotype (Id) by analytical isoelectric focusing followed by in situ labeling with 125I-anti-M511. Antibodies with the M511 Id were shown to be conserved in many mouse strains and were distinct from T15 Id+ anti-PC antibodies. Two complex sets of M511 Id+ bands were observed and these were identified as M511 Id+ antibodies belonging to the IgG1 and IgG3 subclasses. Examination of responses in different individuals of a strain permitted identification of at least 4 to 6 IEF band groups. Thus, the M511 Id is a marker for a family of closely related molecules. Quantitative variations were observed in the expression of the M511 family within a strain and between strains of mice that occurred independently of expression of the dominant T15 Id+ fraction. These results support the concept of an M511 Id family and further suggest that there can be differential control mechanisms governing expression of individual clones or a family of closely related clones.
Synergistic activation by lymphokines and muramyl dipeptide of tumoricidal properties in rat alveolar macrophages.
Authors: Sone S , Fidler I J 
Published: December 2022

Abstract
Alveolar macrophages (AM) from lungs of normal F344 rats can be rendered tumoricidal by incubation in vitro with either muramyl dipeptide (MDP) at a minimum dose of 10 micrograms/ml or undiluted cell-free culture supernatants from mitogen-stimulated F344 rat lymphocytes rich in macrophage-activating factor (MAF) activity. Neither MAF at dilutions exceeding 1:6 nor MDP at doses lower than 10 micrograms/ml activated AM to become tumor cytotoxic. The combination of agents at subthreshold amounts (MAF 1:18; MDP 0.001 to 1 microgram/ml) activated AM to significant levels of cytotoxicity. AM activated by these agents were rendered tumoricidal and destroyed syngeneic, allogeneic, and xenogeneic tumor targets in vitro. The synergism for AM activation between preparations of MAF and MDP required that AM be incubated first with MAF and then with MDP. Even a 15-min treatment of AM with MAF conditioned the cells to respond to subthreshold amounts of MDP and to be rendered tumoricidal. Since treatment of MAF and MDP with polymyxin B did not interfere with macrophage activation, we were able to rule out the possibility that our preparations were contaminated with lipopolysaccharide. Synergism for AM activation was demonstrated also when AM were treated with MAF and MDP encapsulated within liposomes. This finding suggests that the binding of agents to the macrophage surface is not a prerequisite for the synergistic activation of AM by MAP and MDP.
Polyclonal activation of murine B lymphocytes by Fc fragments. III. Characterization of the defect in the ability of the C3H/HeJ mouse to respond to Fc fragments.
Authors: Morgan E L , Weigle W O 
Published: December 2022

Abstract
Spleen cell preparations from the C3H/HeJ mouse were found to be refractory to Fc fragment-induced polyclonal activation. This defect was not a characteristic of all C3H strains, because spleen cells from the histocompatible C3Heb/FeJ strain produced polyclonal antibody in the presence of Fc fragments. The cellular defect was found to be associated with the macrophage population. Macrophages from C3H/HeJ mice were incapable of generating mitogenic Fc subfragments from intact Fc, whereas C3Heb/FeJ performed this function normally. That T cells and B cells from the C3H/HeJ mouse were normal was shown by the fact that C3H/HeJ spleen cells responded to Fc subfragments. Moreover, T cells from C3H/HeJ spleen cell populations could be substituted for C3Heb/FeJ-derived T cells.
Monoclonal antibodies to mouse MHC antigens. II. Antibodies to the H-2Ld antigen, the products of a third polymorphic locus of the mouse major histocompatibility complex.
Authors: Ozato K , Hansen T H , Sachs D H 
Published: December 2022

Abstract
In order to study the fine structure of H-2L, the third H-2 locus of the mouse major histocompatibility complex, we have produced and characterized the monoclonal anti-Ld antibodies secreted by 3 different hybridoma cell lines. Two antibodies were obtained by a specific immunization directed to Ld determinants. Another antibody obtained from an immunization including, but not specific for, an L locus difference was found to detect Ld, and not Kd or Dd molecules. Although the fusions involved an H-2d myeloma variant line, no apparent adverse "autoreaction" was observed in these anti-H-2d antibody-producing hybridoma cells. All 3 antibodies exhibited cross-reactions with the antigens of certain haplotypes, and the reactivity patterns observed corresponded to the previously described alloantigenic specificities H-2.64 and H-2.65. This concordance with known H-2 specificities contrasts with the broad, unique specificity patterns exhibited by most monoclonal antibodies to H-2 antigens and may reflect a difference in the complexity of the polymorphism of the L locus relative to that of the K and D loci. Immunoprecipitation analyses using 1 of the monoclonal antibodies showed that the molecules precipitable by this reagent were indistinguishable from those precipitable by anti-Ld alloantisera. In addition, cross-reactions of Ld, Dq, and Lq molecules were revealed by sequential immunoprecipitation analyses, supporting a close evolutionary relationship of L and D loci.