bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leukocyte procoagulant activity in man: an in vitro correlate of delayed-type hypersensitivity.
Authors: Geczy C L , Meyer P A 
Published: December 2022

Abstract
Human mononuclear leukocytes generate cell-bound procoagulant activity (LPCA) after incubation with an antigen (mumps or tuberculin) to which the donor was previously sensitized. An inhibitor of coagulation appears to be liberated into the extracellular culture fluid during incubation of leukocytes with the sensitizing antigen. Removal of this activity before measuring LPCA resulted in a reliable test that correlated directly with delayed skin reactivity. The assay was particularly sensitive in that cells from weakly sensitized donors who reacted only to high doses of tuberculin (100 TU) in the delayed skin tests produced detectable LPCA in vitro. By contrast cells from weakly sensitized donors did not react to PPD in the lymphocyte blast transformation test or the direct macrophage migration inhibition factor test. The LPCA assay correlated closely with the blast transformation and MIF tests in which cells were used from more strongly sensitized donors who reacted in skin tests with lower doses of tuberculin (1 or 10 TU). The assays were antigen-specific in that cells from donors sensitive to mumps antigen but not to tuberculin reacted only to mumps antigen in vitro. The assay was extremely reproducible; cells from individual donors reacted to the same extent over a period of 8 mo). We propose that the assay system reported here represents an improved method for the measurement of cell-mediated immunity in vitro because it requires fewer donor cells, is technically simpler, and is more sensitive than previously described methods.
Concanavalin A triggers T lymphocytes by directly interacting with their receptors for activation.
Authors: Palacios R 
Published: December 2022

Abstract
Anti-HLA-DR antibodies did not inhibit concanavalin A-(Con A) induced T cell proliferation or the generation of suppressor cells capable of inhibiting immunoglobulin synthesis in autologous mononuclear cells after pokeweed mitogen stimulation. Nylon-wool purified T cells (pretreated with anti-HLA-DR antibody and C) exposed to Con A acquired responsiveness to interleukin 2 (IL 2) and were able to absorb this growth factor, whereas nonlectin-treated cells did not respond to IL 2 and could not absorb it. In the presence of interleukin 1 (IL 1), Con A stimulated the synthesis of IL 2 in purified OKT4+ lymphocytes but not OKT8+ cells. However, in the absence of IL 1, neither resting OKT4+ nor Con A-treated OKT4+ cells produced IL 2. Con A by itself did not directly stimulate macrophages to synthesize IL 1, although it could do so in the presence of OKT4+ but not OKT8+ lymphocytes. In addition, Con A induced proliferation of purified T cells provided IL 1 was supplied to the cultures. Cyclosporin A rendered Con A-treated T cells unresponsive to IL 2, made lectin-stimulated OKT4+ lymphocytes unable to respond to IL 1, and inhibited the synthesis of IL 2. Furthermore, this drug abrogated the Con A-stimulated synthesis of IL 1 by acting on OKT4+ lymphocytes and not on macrophages. Finally, cyclosporin-A suppressed the proliferative response and the generation of suppressor T cells induced by Con A. The following are concluded: 1) HLA-DR antigens do not seem to play any role in the triggering of T cells by Con A, and macrophages participate in lectin-induced activation of T cells mainly by providing IL 1. 2) Cyclosporin-A inhibits activation of T cells by interfering with the mechanism by which Con A stimulates T lymphocytes. 3) Con A triggers T lymphocytes by directly interacting with their receptors for activation.
Correction of defective macrophage differentiation in C3H/HeJ mice by an interferon-like molecule.
Authors: Vogel S N , Weedon L L , Moore R N , Rosenstreich D L 
Published: December 2022

Abstract
C3H/HeJ mice possess macrophages that lose the capacity to bind and phagocytose opsonized sheep erythrocytes (EA) when cultured. This defect in Fc receptor capacity is completely overcome by treatment of macrophage monolayers with extremely low concentrations of a lymphokine-rich, Con A-stimulated spleen cells supernatant. In this study we have pursued a biochemical and functional analysis of the lymphokine-rich supernatant to determine the nature of the specific factor responsible for the restoration of Fc receptor function. The chromatographic behavior and physical properties, its co-elution with anti-viral activity through a sequential purification scheme, the parallel activity of purified beta-interferon in enhancing both the binding and phagocytosis of EA, and the abrogation of factor-induced Fc-mediated phagocytosis with anti-Type II interferon antiserum, strongly support the hypothesis that the active factor is gamma- (Type II or immune) interferon (IFN). These studies suggest gamma-IFN may act as a differentiative signal to the macrophage by facilitating enhanced expression of macrophage surface membrane components.
The in vitro and in vivo induction of anti-double-stranded DNA antibodies in normal and autoimmune mice.
Authors: Fish F , Ziff M 
Published: December 2022

Abstract
To determine whether the existence of anti-dsDNA producing lymphocyte clones is limited to autoimmune strains of mice, spleen cells derived from autoimmune mice (NZB, NZB X NZW F1, MRL) and from normal strains (BALB/c, DBA/2, C57BL/6, C3H/eb) were cultured with E. coli lipopolysaccharide (LPS). DNase-treated supernatants from these cultures were assayed for anti-dsDNA antibodies by employing a sensitive solid-phase radioimmunoassay with poly (dA-dT) as the antigen. All tested spleen cells secreted a small yet significant amount of anti-dsDNA upon stimulation with LPS. There was no difference in the amount or in the heavy chain type of anti-dsDNA secreted by cells from normal and autoimmune strain cells. Evidence of clonal expansion in unstimulated cells was observed only in cultures prepared from older autoimmune animals. Removal of T cells from the spleen cell preparations had no marked effect on the spontaneous or stimulated antibody secretion. Anti-dsDNA antibodies could also be induced in vivo by i.p. injection of LPS into young normal animals. Splenocytes from all tested strains spontaneously secreted anti-ssDNA and anti-TNP antibodies in culture, and these were present at relatively high levels in the serum of unstimulated animals. Stimulation with LPS increased secretion of anti-ssDNA and anti-TNP in all strains in vitro and in five of seven strains in vivo as well. It can be concluded that a) the existence of anti-dsDNA-producing clones is not limited to autoimmune strains, and b) these clones are expanded in old but not in young autoimmune mice. They are not expanded in normal mice at any age.
Lymphokine-mediated microbistatic mechanisms restrict Chlamydia psittaci growth in macrophages.
Authors: Byrne G I , Faubion C L 
Published: December 2022

Abstract
The obligate intracellular procaryote Chlamydia psittaci replicated in cultures of macrophages taken from the peritoneal cavities of unstimulated or thioglycollate-elicited A/J mice. When treated with supernatant fluids (lymphokines) from C. psittaci-immune mice spleen cells that were stimulated for 24 hr in vitro by the mitogen concanavalin A, resident macrophages supplemented with heart infusion broth (8 mg/ml) and elicited macrophages markedly suppressed intracellular chlamydial development. Uptake of the parasites was unaffected by LK-activated macrophages. The LK-induced inhibition was a static rather than a cidal effect. Chlamydial replication was detected 24 to 41 hr after removal of LK and infection with C. psittaci. Evidence that intermediates of oxygen metabolism did not contribute to the microbistatic process in either resident or elicited macrophages was provided by the inability of exogenous catalase, deprivation of glucose, or pretreatment with phorbol myristate acetate (PMA) to reverse LK-induced inhibition of parasite replication.
Demonstration of two distinct antigenic determinants on hepatitis B e antigen by monoclonal antibodies.
Authors: Imai M , Nomura M , Gotanda T , Sano T , Tachibana K , Miyamoto H , Takahashi K , Toyama S , Miyakawa Y , Mayumi M 
Published: December 2022

Abstract
Mice were immunized against hepatitis B e antigen (HBeAg) isolated from sera of asymptomatic carriers of hepatitis B virus. Their spleen cells were fused with mouse myeloma (NS-1) cells, and 5 clones of hybridoma cells secreting antibody against HBeAg (anti-HBe) were isolated. For the production of anti-HBe in large scale, cells were cultivated both in vitro and in the peritoneal cavity of ascitic mice. Although monoclonal antibodies produced by these clones showed a strong reactivity of anti-HBe in hemagglutination tests, individual monoclonal anti-HBe did not reveal any precipitin line in immunodiffusion. When 2 of the 5 monoclonal antibodies were mixed together, however, some combinations showed a precipitin line against HBeAg, whereas others did not. Utilizing solid-phase radioimmunoassay involving a number of combinations of monoclonal antibodies used for solid-phase and radiolabeling, the 5 antibodies were classified into 2 groups. Three of the anti-HBe antibodies were found to be directed to 1 determinant of HBeAg (determinant a); the remaining 2 to the other determinant (determinant b). Determinants a and b were detected on HBeAg in the serum, as well as on the polypeptide of 19,000 daltons (P19) derived from the nucleocapsid of hepatitis B virus. Monoclonal anti-HBe antibodies with different specificities may provide useful tools in delineating the antigenic structure of HBeAg and also in evaluating immune responses of the host directed to its subdeterminants.
Dextran-sulfate: a mitogen for human T lymphocytes.
Authors: Palacios R , Sugawara I , Fernandez C 
Published: December 2022

Abstract
Dextran-sulfate (DxS) induced proliferation of human peripheral blood T lymphocytes but not of adult or neonatal B lymphocytes. The mitogenic activity on T cells by DxS required the presence of accessory cells because DxS was unable to trigger T cells to DNA synthesis in the absence of accessory cells. In addition, DxS stimulated OKT4+8- T cells to produce interleukin 2, a process that also occurred only in the presence of accessory cells. Cyclosporin-A strongly suppressed T cell proliferation induced by DxS by rendering T cells unresponsive to interleukin 2 and by inhibiting the synthesis of this T cell growth factor by OKT4+ T cells. These results indicate that DxS is a mitogen for human T lymphocytes but not for adult or neonatal B lymphocytes. The mechanism by which DxS triggers T cells is discussed.
Concanavalin A supernatant recruits antigen-insensitive IgG memory B lymphocyte precursors into an antigen-sensitive precursor pool.
Authors: Kaattari S L , Rittenberg M B 
Published: December 2022

Abstract
Spleen cells from mice primed to trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH) generate IgG anti-TNP memory responses when stimulated in vitro with either thymus-dependent (TD) or thymus-independent (TI) forms of the hapten. When supernatants from Con A-stimulated spleen cells (Con A Sup) were added to such secondary cultures the TI responses to DNP-dextran or TNP-T4 were augmented; the TD response to TNP-KLH was suppressed. Passage over Sephadex and addition of alpha-methyl-D-mannoside did not inhibit augmentation by Con A Sup, indicating that augmentation did not result from direct action of the lectin on the responding cells. Augmentation occurred equally well in cultures that had been depleted of T cells by treatment with anti-Thy-1.2 and complement. Limiting dilution analyses revealed that Con A Sup increased the frequency of TI-responding precursors approximately threefold while causing a concomitant decrease in TD-responding precursors. To determine the relationship of the additional TI precursors and those normally detected in the absence of Con A Sup, the TI-responding IgG precursors were first eliminated through selective suicide by using DNP-dextran plus BUdR and light treatment; subsequently no TI-responding IgG PFC could be detected to DNP-dextran unless Con A Sup was also added. The data suggest Con A Sup may augment the TI responses to DNP-dextran and TNP-T4 by recruiting additional precursors from a memory cell pool formerly insensitive to these forms of antigen.
Expression of the major cross-reactive idiotype in a primary anti-azobenzenearsonate response.
Authors: Lucas A , Henry C 
Published: December 2022

Abstract
We have studied the occurrence of IgM plaque-forming cells secreting the cross-reactive idiotype (CRI) characteristic of the anti-azobenzenearsonate antibody responses in individual mice of different strains after one injection of the T-independent antigen, p-azobenzenearsonate-Brucella. Under these conditions of stimulation we find that idiotype is not unique to the Igh-1e and Igh-1d allotypes, but is expressed prominently in Igh-1a and Igh-1j strains and to a lesser but significant extent in Igh-1c and Igh-1b strains. We confirmed previous work that idiotype expression in mice hyperimmunized with protein conjugates of azobenzenearsonate is mainly restricted to mice of the Igh-1e allotype, but we find the display to be less marked than in mice given a single injection of the Brucella conjugate. We conclude that the B cell repertoire is inadequately revealed by analysis of serum antibodies of hyperimmune mice. We suggest the apparent correlation of the anti-azobenzenearsonate idiotype to allotype may be influenced by the activity of heavy chain regulatory genes, rather than the presence or absence of structural genes coding for the major CRI. We cannot exclude the possibility that the previously designated CRI-negative strains may express a cross-reactive determinant that is not necessarily a product of the CRI gene family.
Binding properties of IgE receptors on normal mouse mast cells.
Authors: Sterk A R , Ishizaka T 
Published: December 2022

Abstract
Normal rat mast cells and mouse mast cells were purified, and the binding of rat IgE and mouse IgE to IgE receptors was measured. When normal rat mast cells were saturated with either rat IgE or mouse IgE, comparable numbers of IgE molecules bound to the cells. The number of the receptors on rat mast cells was approximately 3 X 10(5)/cell. The forward rate constant, K1, dissociation constant K-1, and equilibrium constant, KA, for rat IgE and mouse IgE were almost similar; KA for rat IgE and mouse IgE were 8 X 10(9) M-1 and 2.5 X 10(9) M-1, respectively. The results indicated that rat IgE and mouse IgE bind to the same IgE receptors on rat mast cells with comparable affinity. It was also found that IgE from the two species bound to mouse mast cells with high affinity. Forward rate constant, K1, for the binding of mouse IgE and rat IgE to IgE receptors on mast cells from BALB/c mice were 1.9 X 10(5) M-1 sec-1 and 1.5 X 10(5) M-1 sec-1, respectively. Mouse IgE and rat IgE dissociate from the receptors with comparable rate (approximately 10(-4) sec-1). However, mouse mast cells appear to have two distinct types of IgE receptors. One type binds both rat IgE and mouse IgE with comparable affinity, whereas the second type binds only mouse IgE. This type of receptor comprises about one-third to one-half of IgE receptors on mast cells of CBA/J mice, and about one-half to two-thirds of IgE receptors in BALB/c mice. Although the binding of rat IgE to these receptors was not detected, the presence of rat IgE along with 125I-mouse IgE interferred with the binding of the latter protein to the receptors. It was suggested that rat IgE might associate with the second type receptors with a forward rate constant comparable to those of mouse IgE, but dissociate rapidly from the receptors.
Bone marrow transplantation across major histocompatability barriers in mice. III. Treatment of donor grafts with monoclonal antibodies directed against Lyt determinants.
Authors: Vallera D A , Soderling C C , Kersey J H 
Published: December 2022

Abstract
We studied the effect of eliminating T cells from donor grafts of mice in a system in which bone marrow was transplanted across major histocompatibility barriers. BALB/c bone marrow (added as a source of hematopoietic stem cells) combined with equal volumes of spleen cells (added as a source of GVHD-promoting cells) was pretreated in vitro with monoclonal anti-Lyt-1.2 or Lyt-2.2 plus absorbed rabbit complement before injection into C57BL/6 total-body-irradiated recipients. Functional activity of anti-Lyt monoclonal antibodies was determined in CML assay. Treatment with anti Lyt-1.2 plus C did not have any anti-stem cell activity, as measured by CFU-S assay, and protected recipients from the onset of lethal GVHD. Treatment with Lyt-2.2 plus C also did not reduce CFU-S; however, mice receiving treated marrow did develop GVHD and were all dead by 2 mo, as were untreated control mice. Surviving "anti-Lyt-1.2 + C chimeras" demonstrated a high percentage of donor mononuclear cells in their peripheral blood. Similar results were obtained when C3H/HeN donor BMS was treated with monoclonal anti-Lyt-1.1 plus C and injected into C57BL/6 recipients. These findings show that monoclonal antibodies directed against determinants unrelated to Thy-1 can eliminate T cells in the presence of C and successfully protect transplanted mice from lethal GVHD. They also suggest that these anti-Lyt antibodies may be useful tools in determining subpopulations of T cells that contribute to the development of GVHD.
Monoclonal anti-deoxyribonucleic antibodies. I. Isotype and specificity studies.
Authors: Jacob L , Tron F 
Published: December 2022

Abstract
Ten monoclonal anti-DNA antibodies generated in three separate fusion experiments performed using nonimmunized B/W spleen cells were studied. Their antigenic specificities were demonstrated to be identical and directed against a conformational determinant of the B helical form of double-stranded DNA (dsDNA). These data suggest that autoantibodies to dsDNA in B/W mice could constitute a homogeneous population.
T cells produce TRF in response to Con A and factors in T cell hybridoma supernatants.
Authors: Raulet D H , Hünig T , Parker D C 
Published: December 2022

Abstract
In recent experiments, a soluble factor (TRF) that mediates the differentiation of anti-immunoglobulin (Ig)-activated B cells to Ig-secreting cells has been identified. TRF works in concert with a growth factor, probably IL 2, in the induction of activated B cells. In previous studies, TRF was identified in culture supernatants of activated T cells and accessory cells, and thus the cellular source (T cell or accessory cell) of the factor was not determined. In the present studies, we succeeded in inducing the production of TRF by T cell populations from which accessory cells had been vigorously depleted. Lymph node cells were depleted of accessory cells by nylon wool adherence and anti-Ia and complement treatment; these cells were activated with Con A and a T cell hybridoma supernatant that contains IL 2. Supernatants from these activated T cell cultures supported the differentiation of anti-Ig-activated B cells to Ig secreting cells. These results show that T cells produce the differentiation factor, and further that they do so in response to ligand (Con A) plus a T cell-derived factor.
Preferential induction of autoantibody secretion in polyclonal activation by peptidoglycan and lipopolysaccharide. I. In vitro studies.
Authors: Dziarski R 
Published: December 2022

Abstract
Peptidoglycan (PG) and lipopolysaccharide (LPS) are bacterial cell wall components that are B cell mitogens and activators of polyclonal antibodies. Using the hemolytic plaque assay and its modifications with protein A-, IgG-, or DNA-coated erythrocytes, we determined the proportions of cells that secrete antibodies specific to various autologous and heterologous antigens in PG- and LPS-stimulated cultures of mouse splenic lymphocytes. Of all PG- and LPS-activated IgM-secreting cells, 47 to 75% produced antibodies specific to mouse IgG; 2.7 to 21% produced IgM antibodies that reacted with bovine IgG; 4.4 to 17%, with single-stranded (ss) DNA; 0.18 to 5.9% with double-stranded (ds) DNA; 0.16 top 3.3%, with bromelin-treated mouse red cells; 0.006 to 0.02%, with intact mouse red cells; and 0.35 to 1.9%, with sheep red cells. A similar distribution of cells secreting these antibodies was observed in unstimulated cultures. However, the absolute numbers of cells secreting these antibodies were substantially higher in the PG- and LPS-stimulated cultures. Similar results were obtained in BALB/c, CBA/H, and C57BL/6 mice. Since these strains of mice have different H-2 types, there was no association of a single H-2 type with the ability to form hgh numbers of autoantibody-secreting cells in vitro. The production of autoantibodies closely resembled polyclonal activation of all immunoglobulin-secreting cells in terms of the kinetics and dose-response. It did not involve any substantial specific anti-PG or anti-LPS response. Further studies on the specificities of polyclonally induced antibodies confirmed the specificity of anti-mouse IgG and anti-ssDNA antibodies. However, the formation of plaques with bovine IgG- or dsDNA-sensitized red cells was due to the cross-reacting anti-mouse IgG or anti-ssDNA antibodies, respectively. These results do not support the popular hypothesis of an equal polyclonal activation of lymphocytes secreting antibodies of all different specificities. Also, if preferential activation of cells secreting rheumatoid factor and anti-ssDNA antibodies occurs in vivo, it may have important pathologic consequences.
Analysis of cerebrospinal fluid and serum of patients with multiple sclerosis by means of anti-idiotypic antisera.
Authors: Nagelkerken L M , van Zoonen-van Exel M , van Walbeek H K , Aalberse R C , Out T A 
Published: December 2022

Abstract
Twelve antisera were prepared, each specific for idiotype(s) of IgG from the cerebrospinal fluid (CSF) of an individual patient with multiple sclerosis (MS). Idiotype-positive (Id(+)) IgG represented 24 to 33% of the CSF-IgG. Radioautographic analysis showed that Id(+)IgG in CSF and in serum had a restricted electrophoretic mobility. From serum of three patients, at least two different noncross-reacting Id(+)IgG fractions were isolated. The anti-Id antisera, which detect IgG considered to be of importance in MS, were used to measure Id(+)IgG in CSF and in serum. Relative to the total IgG, Id(+)IgG was always enriched in CSF, which suggests intrathecal synthesis of such IgG. However, in all patients the absolute concentration of Id(+)IgG was higher in serum than in CSF. Studies attempting to demonstrate cross-reactivity between the IgG of different patients were negative.
Genetic control of experimental autoimmune myasthenia gravis in mice. III. Ia molecules mediate cellular immune responsiveness to acetylcholine receptors.
Authors: Christadoss P , Lennon V A , Krco C J , David C S 
Published: December 2022

Abstract
When MHC congenic and recombinant mice are inoculated with Torpedo acetylcholine receptors (AChR) with adjuvants, the magnitude of autoantibody responses to muscle AChR and the defect of neuromuscular transmission closely parallel in vitro lymphocyte proliferative responses to Torpedo AChR. All of these responses are controlled by gene(s) at the I-A subregion of the H-2 complex. Data presented in this report confirm in back-cross mice that T lymphocyte proliferative responses to AChR are controlled by a Mendelian dominant gene linked to H-2, at the I-A subregion. Lymphocyte responses were eliminated by blocking Ia antigens on lymph node cell surfaces with appropriate anti-I-A alloantisera and by removal of adherent cells. A spontaneous mutation at the I-A subregion in the B6 strain, which resulted in structural alteration of the A beta chain of Ia, converted high responsiveness to AChR to a state of low responsiveness. These data implicate a macrophage-associated Ia molecule in induction of autoimmune responses to AchR, probably in the presentation of AChR to helper T lymphocytes that thereby help B lymphocytes to differentiate into anti-AChR antibody-forming cells.