bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence that Human Leukocyte Inhibitory Factor (LIF) Is an Esterase
Authors: Rocklin Ross E. , Rosenthal Alan S. 
Published: December 2022

Abstract
There are known to be two distinct lymphocyte mediators which inhibit cell migration in vitro, migration inhibitory factor (MIF), which inhibits macrophage migration, and leukocyte inhibitory factor (LIF), which influences the migration of polymorphonuclear leukocytes (PMNL). The present studies were carried out to clarify conflicting reports concerning the sensitivity of MIF activity to a serine esterase inhibitor, diisopropyl phosphofluoridate (DFP). Human MIF and LIF activities were generated by stimulating blood lymphocytes with concanavalin A, filtering the supernatants on Sephadex G-100 gels, and collecting the active fractions of each. MIF and LIF preparations were incubated for 30 min at 37°C with varying concentrations of DFP, dialyzed extensively to remove the inhibitor, and tested on their respective indicator cells. The results showed that LIF activity, but not MIF activity, was irreversibly abolished by DFP (10-3 to 10-5 M). Another irreversible terase inhibitor m-[o-(2-chloro-5-fluorosulfonyl-phenylureido)-phenoxybutoxy] benzamidine, in a dose-dependent fashion, abolished LIF activity. The inactivation of LIF by DFP was concentration, time, pH, and temperature dependent, indicating that DFP served as a substrate for LIF. In addition, LIF preparations (but not MIF) were found to contain hydrolytic activity for certain artificial substrates such as benzoyl arginine ethyl ester and tosyl arginine methyl ester but not glysyl lysyl methyl ester. The response of human monocytes to MIF was not altered by pretreatment with DFP or soybean trypsin inhibitor (STI). In contrast, pretreatment of PMNL with DFP and STI prevented their response to LIF. These studies suggest that LIF, but not MIF, is an esterase.
Pathways of Human B Lymphocyte Differentiation: A Clonal Transition between IgM and IgG Synthesis in Leukemic B Lymphocytes
Authors: Rudders Richard A. , Howard Judith P. 
Published: December 2022

Abstract
Fresh human lymphoma cells from patient Gre were found to have both IgG and IgM associated with only one type of light chain (λ) on the surface membrane. After tissue culture (up to 35 days), enzymatic stripping, reagent absorptions, and ultracentrifugation, similar results were obtained. Double fluorescent labeling studies also demonstrated IgM and IgG on more than 90% of single cells. In experiments designed to study redistribution and subsequent polar capping with double labeling (rhodamine and fluorescein) techniques, we found that 1) anti-IgG or IgM and λ reagents formed mixed polar caps, 2) anti-IgG and IgM formed polar caps which suggested segregation of the two labels, and 3) prior staining with either heavy chain antiserum did not block subsequent staining with the other. We interpret these findings as suggesting the presence of a clonal switch mechanism involving IgM and IgG synthesis operating at the B lymphocyte level, presumably via an alteration in the CH gene. Additionally, when secretory Ig was looked for, we found evidence for intracellular (secretory) λ-chain synthesis without corresponding heavy chain synthesis. This latter observation further emphasizes the divergence of the secretory and membrane Ig synthetic pathways proposed by other investigators.
Strain Variation in BCG-Induced Chronic Pulmonary Inflammation in Mice
Authors: Allen Elizabeth M. , Moore Vernon L. , Stevens James O. 
Published: December 2022

Abstract
C57BL/6 mice (haplotype H-2b) responded in a dose-dependent fashion to killed BCG by marked enlargement of the spleen and lung. Neither CBA nor C3H mice (haplotype H-2k) responded to such treatment. Pulmonary inflammation in responder B6 animals was characterized by a marked chronic interstitial and alveolar granulomatous process, and was accompanied by occasional granulomata, hyperemia, and loss of architecture in the spleen. Inflammation in non-responder CBA and C3H animals was minimal in both the lung and spleen. The response does not appear to be controlled by genes within the major histocompatibility complex, but is associated with a C57 background. B10.BR mice (responder background, H-2k) were responder animals and C3H.SW mice (nonresponder background, H-2b) were nonresponders. In addition, all animals tested with a C57 background were responders even though two of these strains were not H-2b (C57BL/Ks, H-2d and C57Br/cd, H-2k). The resolution of the mechanism of genetic control of this response in mice may provide information relevant to possible genetic control of chronic pulmonary inflammation in man.
Lymphocytes Binding Polyriboadenylic Acid and Synthesizing Antibodies to Nucleic Acids in Autoimmune and Normal Mice
Authors: Sawada Shigemasa , Pillarisetty Rao J. , Michalski Joseph P. , Palmer Donald W. , Talal Norman 
Published: December 2022

Abstract
Splenic lymphocytes from both normal and autoimmune mice bind significant quantities of polyriboadenylic acid (poly rA) when incubated with radiolabeled poly rA for 40 min at 37°C. This poly rA binding is specifically inhibited by an excess of nonradioactive poly rA and by anti-mouse immunoglobulin. Poly rA binding is decreased by exposing spleen cells to Pronase and is restored by subsequent culture for 18 to 72 hr. Poly rA-binding activity is associated more with bone marrow-derived than with thymus-derived lymphocytes. These results suggest the presence of autoantigen-binding lymphocytes in normal as well as autoimmune mice.
Furthermore, spleen cells from normal and autoimmune mice cultured for 72 hr synthesize and secrete antibodies to poly rA and DNA. These antibodies can be recovered from the culture supernatants by a solid immunoadsorbent technique and antibody immunoprecipitation. The synthesis of antibodies to nucleic acids by normal spleen cells suggests that autoreactive lymphocytes may be released from normal immunoregulatory control during in vitro culture conditions.
Isolation of the Cytoplasmic Granules of Guinea Pig Basophilic Leukocytes: Identification of Esterase and Protease Activities
Authors: Dvorak Harold F. , Orenstein Neil S. , Dvorak Ann M. , Hammond M. Elizabeth , Roblin Richard O. , Feder Joseph , Schott Chester F. , Goodwin Jane , Morgan Ellen 
Published: December 2022

Abstract
Procedures were developed for isolating highly purified cytoplasmic granules of basophilic leukocytes from guinea pig peripheral blood. The methods involved disruption of cells in 0.34 M sucrose followed by a series of membrane filtrations and fractionation on sucrose density gradients. These preparations, up to 95% pure basophil granules by electron microscopy, contained a mixture of neutral esterases-proteases including caseinolytic activity; both trypsin- and chymotrypsin-like serine hydrolases were identified by means of appropriate inhibitors. Localization of at least one such activity to the basophil granule was confirmed by a cytochemical method; this activity was absent in contaminating lymphocytes and eosinophils. By contrast, several lysosomal enzymes, lactic dehydrogenase, and plasminogen activator activity, present in cell homogenates, were absent from purified granules.
The granule matrix of guinea pig basophils, unlike the cytoplasmic granules of other granulocytes or mast cells, was little altered by high or low salt concentration but was disrupted into insoluble fragments by 0.01 N HCl and by Triton X-100. Granules were solubilized by papain and by urea-SDS but enzyme activity was destroyed. Triton X-100 incubation with freeze-thawing proved to be the optimal method for extracting esterase activities. Esterase activities were not released from basophils under conditions of anaphylactic degranulation that liberated the great majority of basophil granule histamine.
Effects of α-Fetoprotein on Murine Immune Responses
Authors: Sell S. , Sheppard H. W. , Poler Mark 
Published: December 2022

Abstract
In vitro and in vivo experiments failed to identify a consistent “immunosuppressive” or “immunoregulatory” role for α-fetoprotein (AFP) in the rat. Both normal and AFP-rich sera inhibited Con A, PHA, and MLR proliferation responses of lymphocyte cultures in vitro equally well, in spite of up to 100,000-fold differences in AFP concentration. AFP-rich sera also had no effect on the antibody response of the rat in vivo. Purified AFP from amniotic fluid inhibited the PHA response at concentrations of 100 µg/ml. Purified albumin was also inhibitory, but at 1 log higher concentration. Purified AFP from tumor sera was not inhibitory at 100 µg/ml for Con A, PHA, or MLR reactions and only inhibited PHA stimulation at medium concentrations greater than 1000 µg/ml. The role of AFP as an immunosuppressive agent, particularly in reference to survival of mammalian fetuses, should be reconsidered.
Cytotoxic Effects of Normal Sera on Lymphoid Cells
Authors: Budzko Delia B. , Kierszenbaum Felipe , Waksman Byron H. 
Published: December 2022

Abstract
In the present study, we have examined the identity of the mouse lymphoid cells subject to nonspecific killing by normal guinea pig serum (GPS). In parallel cytotoxicity assays in which the number of cells was varied over a 12-fold range, with all other conditions kept the same, the proportions of cells killed were virtually constant, indicating that a specific cell subpopulation acted as target. Spleen cells surviving treatment with GPS were found to be incapable of responding to the T cell mitogens phytohemagglutinin-P and concanavalin A but responded well to stimulation with endotoxic lipopolysaccharide (LPS), a B cell mitogen, suggesting either a direct or indirect selective effect of GPS on T cells. Similar results were obtained with C4-deficient GPS. LPS-induced DNA synthesis was identical in spleen cells treated with either GPS or anti-Thy-1.2 antibody plus a noncytotoxic source of complement. Spleen cells surviving treatment with anti-Thy-1.2 antibody plus complement were found to be insensitive to GPS cytotoxicity. Conversely, prior incubation of the spleen cells with GPS resulted in the killing of all cells subject to lysis by anti-Thy-1.2 and complement. Spleen cells from nu/nu mice and bone marrow cells from normal mice showed minimal sensitivity to GPS cytotoxicity. A close similarity was observed between the percentages of cells killed by GPS in various lymphoid cell populations and the known proportions of T cells in these populations. In cytotoxicity assays in which normal and T cell-enriched (by passage through nylon wool columns) spleen cell populations were tested with both GPS and anti-Thy-1.2 plus complement, lysis by the two techniques was always comparable. The present results suggest strongly that mouse T cells are selectively killed by GPS and that this cytotoxicity can be used to monitor T cell proportions in mouse lymphoid cell populations with the same efficiency as with the use of anti-Thy-1.2 antibody plus complement.
Suppression of the Human Autologous Mixed Lymphocyte Reaction by Physiologic Concentrations of Hydrocortisone
Authors: Ilfeld David N. , Krakauer Randall S. , Blaese R. Michael 
Published: December 2022

Abstract
Normal human T lymphocytes respond with vigorous proliferation when exposed in vitro to autologous irradiated lymphocytes enriched in B cells. In this report we examined the effect of various humoral factors that might play a role in the regulation of this autologous MLR. Neither fresh autologous plasma, thymic factors, nor hepatoma-derived α-fetoprotein had any significant suppressive effect on the autologous (or allogeneic) MLR. In contrast, over 98% suppression of the autologous MLR occurred with addition of 4 × 10-7 M hydrocortisone succinate. Interestingly, the presence of 2 to 8 × 10-8 M hydrocortisone during the autologous MLC suppressed 62 to 84% of the proliferation, whereas it did not suppress proliferation in the allogeneic MLC. Kinetic studies demonstrated that the predominant suppression of proliferation in the autologous MLC by hydrocortisone occurred during the first few days of culture and that by 100 hr of culture (which is before most of the DNA synthesis occurs) the addition or removal of hydrocortisone had no further effect on the reaction. The presence of hydrocortisone during just the first 6 hr of the autologous MLC also had no suppressive effect on proliferation. Thus, hydrocortisone alters critical functions at a cellular level without causing destruction or other irreversible effects on potentially autoreactive lymphocytes. Furthermore, marked suppression of the autologous MLR without any suppression of the allogeneic MLR was observed with concentrations of free cortisol equivalent to those found in human plasma, suggesting that hydrocortisone may have a physiologic role in the regulation of such T cell autoreactivity in vivo.
Studies of the Mechanism by Which B Cells Permit Mixed Lymphocyte Reactions between Immunocompetent Thymus Cells
Authors: Dyminski J. W. , Smith R. T. 
Published: December 2022

Abstract
The mechanisms by which a critical ratio of peripheral lymphoid helper cells permit a proliferative MLR response between congenic immunocompetent thymus cell subpopulations was investigated. The helper cell was found to be contained in a subpopulation of B cells on the basis of sensitivity to anti-Ig and complement, resistance to anti-Thy-1.2, adherence to nylon columns, and ability to form EA and EAC rosettes with sheep erythrocytes. The maximal helper cell effect was obtained in those combinations in which helper was syngeneic for responder. Helper cells of F1 hybrid origin or syngeneic to stimulator cells were less effective. Kinetic studies indicated that the first of the sequence of events is helper cell-stimulator cell interaction, followed by triggering of responder proliferation generating a subset of cytotoxic cells. Helper activity was trypsin sensitive, and present in solubilized preparation of peripheral cells. Helper activity of intact cells was nearly matched quantitatively by critical ratios of polyclonal IgG, IgG subclasses, and IgG fragment preparations, but little activity was supplied by IgA and IgM preparations. Kinetics studies of IgG helper activity indicate dose-response effects and sequence of interaction similar to those found for whole B cells. A hypothesis is offered to explain how the B-helper or its product may permit an otherwise nonreactive MLR between immunocompetent thymus cells.
A Carbohydrate-Containing Antigen from Trypanosoma cruzi and Its Detection in the Circulation of Infected Mice
Authors: Gottlieb Michael 
Published: December 2022

Abstract
A polysaccharide-containing fraction has been prepared from the water-soluble material of a phenol-water extract of epimastigote forms of Trypanosoma cruzi. Sera from rabbits immunized with this material have been used to detect trypanosome-derived polysaccharide in plasma of mice acutely infected with this parasite. The polysaccharide nature of the circulating antigen is suggested by its heat stability, resistance to proteinase and nucleases, and destruction by sodium metaperiodate, as well as by its periodic acid-Schiff staining and precipitation with concanavalin A. The antigen appears to be present in different strains of the parasite and in different stages in the life cycle of the parasite.
Complement-Mediated Dissociation of Antibody from Immobilized Antigen
Authors: Miller Gary W. 
Published: December 2022

Abstract
Previous studies that showed that complement (C) can convert insoluble Ag-Ab precipitates into soluble immune complexes suggested that activated C components might be able to dissociate Ab from Ag. The present study directly examined this possibility by measuring the dissociation of radiolabeled Ab from immobilized Ag in the presence or absence of active complement. Small polystyrene test tubes were coated with BSA (Ag), and the coating was cross-linked with glutaraldehyde to ensure its stability. Then, 125I-labeled 7S fraction of mouse anti-BSA was allowed to bind to the BSA-coated tubes; controls showed that the binding was specific. The release of labeled Ab from the tubes was measured in the presence of fresh serum or decomplemented serum at 37°C. Active complement markedly increased both the rate of release and the final amount of Ab released. Once begun, the release of Ab could continue for some time in the absence of fluid-phase complement. Controls included duplicate sets of tubes coated with radiolabeled BSA in which unlabeled Ab was bound. These controls showed that, although minute amounts of BSA were unavoidably lost from the tubes, this loss could not account for the observed release of Ab. The ability of the released Ab to rebind to fresh BSA-coated tubes was also examined; it was found that C-released Ab could rebind nearly as efficiently as spontaneously released Ab. The results are completely compatible with the “intercalation” hypothesis developed to explain the C-mediated solubilization of immune aggregates.
Macrophages Suppress CTL Generation in Rat Mixed Leukocyte Cultures
Authors: Weiss Arthur , Fitch Frank W. 
Published: December 2022

Abstract
The generation of CTL in rat MLC was actively suppressed by a cell population present in spleen cell preparations from normal rats. These suppressor cells were characterized by using a variety of cell fractionation techniques. Suppressor cells were removed by passage of spleen cells through nylon wool columns or by treatment with carbonyl iron. Suppressive activity was present in the mononuclear cell fraction of spleen cells obtained by Ficoll-Hypaque density gradient centrifugation. After velocity sedimentation at unit gravity, enrichment of suppressive activity was demonstrated in the fractions containing large cells as compared to the fractions containing small cells. Populations rich in macrophages were shown to have similar suppressive activity upon CTL induction in MLC. These studies suggest that macrophages present in normal rat spleen cell preparations account for the difficulty in generating CTL in MLC prepared with rat cells.
Transient Suppression of the Humoral Immune Response Mediated by a Factor Derived from Specifically Activated, Doubly Primed Lymphoid Cells
Authors: Kempf Kenneth E. , Rubin Arnold S. 
Published: December 2022

Abstract
In cultures of sheep erythrocyte- (SRBC) stimulated spleen cells from mice immunized with tetanus toxoid (TT) and horse erythrocytes (HRBC) 30 to 90 days earlier, the addition of both HRBC (day 0) and TT (day 2) resulted in significant suppression of the anti-SRBC plaque-forming cell (PFC) response compared to the response of similar cultures maintained without the priming antigens. The observed inhibition was due to the presence of a soluble factor that was released into the supernatant fluid of the specifically stimulated, primed population of lymphoid cells between 72 and 120 hr after culture initiation. The active mediator, a macromolecule of ∼∼24,000 daltons as determined by gel filtration over Sephadex G-150 and Ultrogel AcA 44, was suppressive when added within 24 hr, but not 48 hr, of assay for PFC against the reference SRBC antigen. The transiently acting soluble suppressor (TASS) was not overtly cytotoxic since total cell recovery and viability were unaffected in its presence. The results presented here are discussed in relation to a possible mechanism of action in which the negative regulation of immunoglobulin production is favored once a minimum level of immune reactivity is reached.
Enhancement of the PGE1 Response of Macrophages by Concanavalin A and Colchicine
Authors: Gemsa Diethard , Steggemann Ludwig , Till Gerd , Resch Klaus 
Published: December 2022

Abstract
The effects of concanavalin A (Con A) and colchicine on the prostaglandin E1 (PGE1)-mediated cyclic AMP generation in rat peritoneal macrophages have been studied. Although Con A and colchicine by themselves did not affect cyclic AMP levels, they greatly enhanced cyclic AMP production induced by PGE1. There was not only augmentation of cyclic AMP levels at maximally active concentrations of PGE1, but also an increased sensitivity to low (inactive) concentrations of PGE1. Except for lentil lectin, none of the other lectins affected PGE1 sensitivity whereas lumicolchicine was as effective as colchicine. In addition, both Con A and colchicine raised the sensitivity to isoproterenol and choleraenterotoxin. Although details of the mechanisms by which Con A or colchicine influenced the membrane-bound adenyl cyclase and PGE1 receptors remain unclear, these observations suggest that certain alterations of the cell membrane may render macrophages more susceptible to the regulating effects of prostaglandins.
Binding of N-Acetylgalactosamine-Containing Compounds by a Human IgM Paraprotein
Authors: Naiki Masaharu , Marcus Donald M. 
Published: December 2022

Abstract
A serum that contains a monoclonal human IgM paraprotein (McG) agglutinates protease-treated human erythrocytes and binds glycosphingolipids that possess a terminal nonreducing N-acetylgalactosaminyl residue in either the α or β anomeric configuration. The approximately equal reactivity of McG with both anomers of N-acetylgalactosamine was unexpected because most immunoglobulins that bind saccharides exhibit a marked preference for one anomeric configuration.
The major receptor for this protein in normal group O erythrocytes is globoside, the blood group P antigen: Ga1NAc(β,1→3)Gal(α,1→4)Gal(β,1→4)G1c-ceramide. Erythrocytes of the rare Pk and p phenotypes lack globoside, and the former are not agglutinated by McG. The McG receptor in p erythrocytes, which are agglutinated as strongly as normal cells, appears to be a crossreactive glycolipid that contains a much larger number of sugar residues than globoside.
Inhibition of Human Lymphocyte Transformation by Human α-Fetoprotein (HAFP); HAFP Monomers and Multimers and a Resistant Lymphocyte Subpopulation
Authors: Yachnin Stanley , Lester Eric P. 
Published: December 2022

Abstract
We have previously shown that human α-fetoprotein (HAFP) inhibits the response in vitro of human lymphocytes to a variety of mitogenic stimuli. In this report we present evidence that HAFP preparations containing dimeric and trimeric forms are no more inhibitory than HAFP monomeric isolates. HAFP isolates of low inhibitory potency cannot impede the capacity of high-potency HAFP to inhibit lymphocyte transformation. Since lymphocyte responses to phytomitogens or anti-human thymocyte antiserum cannot be totally suppressed by increasing doses of HAFP, we conclude that human lymphocyte preparations contain a population of lymphocytes resistant to the inhibitory action of HAFP.
Inflammatory Cells in Solid Murine Neoplasms
Authors: Gillespie G. Yancey , Hansen Christopher B. , Hoskins Ronald G. , Russell Stephen W. 
Published: December 2022

Abstract
Highly purified suspensions of intratumoral T lymphocytes, recovered 11 and 13 days after induction of regressing or progressing Moloney sarcomas, were compared in their ability to lyse specifically the MSC cells used for tumor induction. Cytolytic activity, expressed in terms of lytic units/106 T cells, was similar for intratumoral T cell suspensions obtained 11 days after induction of either regressing (3.1 ± 1.3 LU/106 T cells) or progressing (4.3 ± 1.8) neoplasms. By 13 days post-induction, regressing tumors contained T lymphocytes with an increased cytolytic activity (11.1 ± 4.5) whereas those from progressing tumors were strikingly less able to kill MSC cells (≤ 0.2). This dramatic loss in cytotoxicity could not be attributed to errors associated with the enzymatic disaggregation method, inhibition by copurified endogenous tumor cells, or immunosuppression induced by viral infection. The changes in functional activity of intratumoral T lymphocytes from the two types of sarcoma appeared to be correlated with the stage of neoplasia. In this model system, cytolytic activity of T lymphocytes increased during spontaneous tumor regression whereas losses in cytotoxicity occurred coincident with the onset of inexorable progression.