bluuebunny/crossref_metadata_2025_split huggingface dataset:
Splenic Suppressor Cells and Cell-Mediated Cytotoxicity in Murine Schistosomiasis
Authors: Coulis Paul A. , Lewert Robert M. , Fitch Frank W. 
Published: December 2022

Abstract
An impairment of the capacity to generate alloantigen-specific cytotoxic T lymphocytes (CTL) was observed in mixed lymphocyte cultures (MLC) established with spleen cells from mice infected with Schistosoma mansoni. This impairment, which was observed as early as the eighth week of infection, could be abrogated by the fractionation of spleen cell suspensions by the carbonyl iron/magnet method prior to the establishment of MLC. Cocultivation of normal spleen cells with increasing numbers of splenocytes from S. mansoni-infected syngeneic mice resulted in a dosage-dependent suppression of CTL generation. This “infectious suppression” was not sensitive to antiserum against mouse thymic lymphocyte antigen (MTLA).
The present studies suggest the role of a macrophage rather than a T cell as the suppressor cell in this model of cell-mediated immunity in schistosome-infected mice.
Activation of Human B Lymphocytes
Authors: Haynes Barton F. , Fauci Anthony S. 
Published: December 2022

Abstract
The kinetics and mechanisms of suppression of the PWM-induced PFC response of human PB lymphocytes by Con A-activated suppressor cells were investigated. It was necessary that Con A suppressor cells be present early in the preocess of activation of human B cells toward antibody synthesis, but maximal suppression of the PFC response occurred later in the culture period. In addition, Con A-activated cells, although suppressing the PFC response to PWM greater than 90% of control, did not significantly suppress the blastogenic response to PWM after 3 or 5 days in culture. On the contrary, after 3 days in culture, background tritiated thymidine incorporation as well as tritiated thymidine incorporation to PWM stimulation was increased when Con A suppressor cells are added to fresh autologous peripheral blood lymphocytes. This increased blastogenic response after three days most likely represented an autologous mixed lymphocyte reaction (MLR) of Con A suppressor cells against fresh autologous non-T cells. The induction of autoreactive cells may be one of several modes of suppression of PFC responses by Con A activated suppressor cells.
Nonimmunospecific Protein-Protein Interactions of IgG: Studies of the Binding of IgG to IgG Immunoadsorbents
Authors: Nardella Francis A. , Mannik Mart 
Published: December 2022

Abstract
Nonimmunospecific interactions of IgG and IgG-agarose columns were systematically studied under varying conditions. Nonimmunospecific binding to the columns was primarily due to protein-protein interactions. These nonimmunospecific protein-protein interactions of IgG were enhanced with heat-induced or chemical aggregation of IgG, low pH, low ionic strength (at pH above 4), or low temperature. Conversely, this binding was decreased with proteolytic fragmentation of IgG, high ionic strength (at pH above 4), or temperatures above 4°C. Chemical modification of IgG by acetylation, formalinization, carbamylation, or reaction with 1,2-cyclohexanedione significantly decreased these interactions. These observations suggest that above pH 4, ionic interactions caused the protein-protein binding. Below pH 4, hydrophobic interactions presumably play a major role.
These results permit the development of a rational methodology for avoiding nonimmunospecific protein-protein interactions in immunologic procedures for detection, isolation, or quantification of rheumatoid factors and other antibodies to IgG.
Plasminogen Activator of Guinea Pig Basophilic Leukocytes: Probable Localization to the Plasma Membrane
Authors: Dvorak Harold F. , Orenstein Neil S. , Rypysc Jane , Colvin Robert B. , Dvorak Ann M. 
Published: December 2022

Abstract
The plasminogen activator (PA) activity of guinea pig basophil-enriched leukocyte preparations was localized to basophils, and not to contaminating lymphocytes and eosinophils, by correlating PA activity with basophil frequency and, more directly, by means of an improved cytochemical method here described. PA activity was fully expressed in living cells in the absence of immunologic stimuli and was suppressed/lost to a variable extent by different techniques of cell disruption. Conversely, killed, but not living, basophils expressed significant plasminogen-independent fibrinolytic activity, presumably reflecting access of cytoplasmic proteases of broken basophils to fibrin substrate. The PA activity of intact cells was destroyed by gentle trypsinization under conditions that did not impair cell viability. When disrupted cells were ultracentrifuged on a sucrose density gradient, PA activity was absent from purified granules and was confined to fractions containing cell membranes. The simplest explanation of these data is that guinea pig basophils have PA activity associated with their plasma membranes. This conclusion has several important implications for basophil functions in cell-mediated and other immunologic reactions in vivo.
Delineation of Spontaneous Erythrocyte Autoantibody Responses of NZB and Other Strains of Mice
Authors: Deheer David H. , Linder Ewert J. , Edgington Thomas S. 
Published: December 2022

Abstract
Four anti-erythrocyte autoantibody responses (anti-X, anti-HB, anti-HOL, and anti-I) that occur spontaneously in mice have been characterized with regard to antigenic specificities, predominant immunoglobulin class, and pathogenetic importance. Each autoantibody response exhibits specificity for an independent erythrocyte membrane autoantigen (X, HB, HOL, or I) or a soluble analogue (SEA-X or SEA-HB) present in the plasma. The anti-X response, unique to NZB mice, is directed to a normally exposed murine erythrocyte autoantigen, whereas the anti-HB response is directed to a cryptic erythrocyte autoantigen exposed by limited enzymatic cleavage of the membrane. The anti-I response also is directed to a cryptic but distinct autoantigen, and anti-HOL autoantibodies react with an erythrocyte autoantigen located at the cytoplasmic surface of the membrane.
Analysis of the predominant immunoglobulin class of each of the autoantibodies has demonstrated that anti-HB and anti-I antibodies are predominantly of IgM class, whereas anti-X and anti-HOL antibodies are IgG immunoglobulins. Only anti-X and anti-HB autoantibodies are recovered from Coombs' positive erythrocytes from NZB mice and erythrocytes with surface C3 are detected only in NZB mice greater than 9 months of age. These data suggest that only the anti-X and anti-HB responses are pathogenetically implicated in the autoimmune hemolytic anemia of NZB mice.
Leukocyte Complement: Neoantigens of the Membrane Attack Complex on the Surface of Human Leukocytes Prepared from Defibrinated Blood
Authors: Sundsmo John S. , Kolb William P. , Müller-Eberhard Hans J. 
Published: December 2022

Abstract
The neoantigenic determinants (neoAg) which have been identified in the human C5b-9 membranolytic C complex were detected here by the direct fluorescent antibody technique on the surface of 27 ± 11% of viable peripheral blood leukocytes (PBL). The cells were prepared from defibrinated blood by sedimentation on Ficoll-Hypaque. Specificity of the antisera was established by quantitative inhibition of the fluorescent staining reaction, and of agglutination of EAC1-7, by highly purified C5b-9 complex. No inhibition was observed with fresh normal human serum. The majority of the PBL with surface neoAg was found in the B lymphocyte subpopulation that failed to form rosettes with sheep erythrocytes. NeoAg on B lymphocytes was removed to differing degrees by trypsin, papain, or pepsin treatment, and by maintaining the cells at 4°C for 20 hr in serum-free medium. The individual components, C5, C6, C7, C8, and C9, were also detected on the surface of PBL. With differential fluorescent stains, C5 and neoAg as well as C8 and neoAg could be detected on the same cells. The results indicate that viable B lymphocytes prepared from defibrinated blood, have the components of the membrane attack complex of C on their surface. The concomitant occurrence of the neoAg indicates that these proteins are present at least in part in the form of the assembled terminal complex.
Stimulation of the Synthesis and Release of Lipids in Tumor Cells under Attack by Antibody and C
Authors: Schlager Seymour I. , Ohanian Sarkis H. , Borsos Tibor 
Published: December 2022

Abstract
Antibody-sensitized line-1 or line-10 tumor cells treated with GPC (TAC) incorporated fatty acids into complex cellular lipids and released increased amounts of fatty acids within 5 to 10 min after the addition of GPC as compared to control cells. This effect was dependent on the concentration of GPC used; however, under conditions where the cells were not killed, the enhanced synthesis and release of lipids were not dependent on the antibody concentration used to sensitize the cells. Treatment of the cells with antibody alone, GPC alone, or antibody plus heat-inactivated GPC did not result in enhanced synthesis or release of lipids. No enhancement in DNA, RNA, or protein synthesis in TAC was noted. Line-1 cells, which can be killed by GPC when sensitized with excess anti-Forssman IgM antibody, demonstrated enhanced lipid synthesis within 1 to 3 min after the addition of GPC to the antibody-sensitized cells, before measurable killing of the cells had occurred. This effect persisted in the surviving cells when tested 5 and 10 min after the formation of TAC. Addition of GPC deficient in C4 to antibody-sensitized cells did not result in enhanced lipid synthesis or release. These data suggest that the synthesis of macromolecules of which lipids are a major component is of central importance for the ability of the cells to resist antibody-GPC mediated attack.
Control of Human B Lymphocyte Responsiveness: Enhanced Suppressor T Cell Activity after in vitro Incubation
Authors: Lipsky Peter E. , Ginsburg William W. , Finkelman Fred D. , Ziff Morris 
Published: December 2022

Abstract
Human peripheral blood mononuclear cells (PBM) lost the capacity to generate immunoglobulin-secreting cells (ISC) in response to pokeweed mitogen (PWM) after a period of preincubation in vitro. When fresh PBM were co-cultured with preincubated PBM their response to PWM was inhibited, indiating that enhanced suppressor activity developed in the aged PBM concomitant with the loss of PWM responsiveness. Suppressor cell activity of aged PBM was present within the T lymphocyte population. The suppressor T cell inhibited PWM responsiveness of autologous and homologous PBM to an equivalent degree. The action of the suppressor cell was abrogated by inhibitors of DNA synthesis or by hydrocortisone. A suppressor T cell population with similar characteristics was found in freshly prepared PBM before in vitro incubation. Expansion of this suppressor T cell population during preincubation required cell division. There was no change in the functional capability of the helper T cell population as a result of similar in vitro culture. These observations indicate that a T cell population capable of suppressing PWM-induced generation of ISC can be selectively expanded by in vitro incubation of normal human PBM without additional mitogenic stimulation. Moreover, these data emphasize that control of B lymphocyte differentiation involves a critical interrelationship between T lymphocyte subpopulations exerting both positive and negative influences.
Production of Migration Inhibition Factor (MIF) and an Inducer of Plasminogen Activator (IPA) by Subsets of T Cells in MLC
Authors: Newman Walter , Gordon Saimon , Hämmerling Ulrich , Senik Anna , Bloom Barry R. 
Published: December 2022

Abstract
Supernatants of murine spleen cells activated in MLC contain both MIF and a factor which induces plasminogen activator secretion by macrophages. These activities are not found in supernatants of unstimulated T cells in control (syngeneic) cultures. Because no plasminogen activator or fibrinolytic activity was detected in the lymphocyte supernatants directly, but appeared when supernatants were added to macrophages, we infer that production of this activity is induced in macrophages by an inducer of plasminogen activator (IPA).
IPA and MIF activities are first detected after 24 hr of MLC; peak activity occurred on day 3. Both factors eluted from Bio-Gel P-100 columns in the range of Kd 0.15 to 0.25 (m.w. range 25,000 to 60,000 daltons).
Production of both factors in this system required the presence of T cells. In experiments using anti-Ly 1 and anti-Ly 2,3 sera + C, it was observed that both the Ly 1 (helper-type) and Ly 2,3 (cytotoxic/suppressor-type) T cell subpopulations produced each mediator. It is likely that the production of mediators by individual T cell subsets in vivo is not restricted by their intrinsic capabilities, but rather by factors which determine their activation. These results point to the possible importance of both T cell subpopulations in activating macrophages, and indirectly in aspects of tissue injury resulting from cell-mediated immune reactions involving protease activation.
Since IPA correlated with MIF in terms of activity (0.78 coefficient of correlation), kinetics of production, gel filtration characteristics, and production by T cell subsets, and because the assay for plasminogen activator is a sensitive and reproducible one, it should be increaseingly useful in in vitro studies of cell-mediated immunity.
DAN Synthesis and Proliferation of Human Lymphocytes in Vitro
Authors: Bernheim Jan L. , Mendelsohn John 
Published: December 2022

Abstract
DNA newly synthesized by phytohemagglutinin-(PHA) stimulated human lymphocytes has been analyzed for the possibility that all DNA synthesis may not represent premitotic genome duplication. Equilibrium density gradient characterization of bromodeoxyuridine-(BUdR) substituted DNA demonstrates semi-conservative DNA replication, without evidence for repair synthesis. Experiments to detect selective replication (amplification) of a portion of the DNA involved measurement of reassociation kinetics as well as measurement of the kinetics of BUdR appearance in prelabeled DNA. The presence of large quantities of amplified DNA has been excluded, although amplification cannot be ruled out completely by these techniques. Finally, the kinetics of DNA release from dead lymphocytes is characterized, and factors tending to reduce the complexity of released, labeled DNA are identified.
Enhancement of Carrier-Specific Helper T Cell Function by the Synthetic Adjuvant, N-Acetyl Muramyl-l-Alanyl-d-Isoglutamine (MDP)
Authors: Sugimoto Masanobu , Germain Ronald N. , Chedid Louis , Benacerraf Baruj 
Published: December 2022

Abstract
The adjuvant effect of a synthetic peptidoglycan, muramyl dipeptide (N-acetyl muramyl-l-alanyl-d-isoglutamine, MDP), was studied by using the anti-Tnp PFC and hemagglutinin responses of BALB/c mice to hapten-carrier conjugates. Administration of Tnp-OVA and MDP in saline to mice, followed 2 weeks later by a boost of Tnp-OVA in saline, led to significantly higher IgM and IgG anti-Tnp PFC and total anti-Tnp-hemagglutinin responses than those obtained in mice not treated with MDP in the initial immunization. A similar adjuvant effect by MDP on anti-hapten PFC responses was seen if mice were primed with KLH together with MDP and challenged with Tnp-KLH 2 weeks later. This apparent effect on carrier priming for helper function was confirmed and quantitated by double adoptive transfer experiments with graded numbers of spleen cells from KLH ± MDP-primed mice and a fixed number of haptenprimed spleen cells from syngeneic Tnp-OVA immunized animals. These data suggest that at least one mode of action of the synthetic adjuvant MDP is via the enhanced stimulation of the helper T cell function.
Interpretation of 51Cr-Release Data: A Kinetic Analysis
Authors: Thoma John A. , Touton Mary H. , Clark William R. 
Published: December 2022

Abstract
An analysis of 51Cr-release data from cell-mediated cytotoxicity assays, plotted in the form of effector cell dilution curves, is analyzed in detail in terms of a saturation kinetics model for effector-target interaction. The effect of nonimmune (bystander) cells in the effector population is particularly examined. The theoretical development of the saturation model predicts that, at low concentrations of target cells, increasing proportions of bystander cells should broaden the range of effector cell concentration required to achieve a given increment of target cell lysis, but that at high target cell concentration this effect should disappear. Experimental validation of this prediction is presented.
Ionophore A 23187-Induced Production of Slow Reacting Substance of Anaphylaxis (SRS-A) by Rat Peritoneal Cells in Vitro: Evidence for Production by Mononuclear Cells
Authors: Bach Michael K. , Brashler John R. 
Published: December 2022

Abstract
A slow reacting substance is produced when mixed peritoneal cells from rats are incubated with low concentrations of the calcium ionophore A 23187 in the presence of 0.01 M cysteine. The product resembles slow reacting substance of anaphylaxis (SRS-A), if it is not identical to it, based on its behavior during chromatography on Amberlite XAD-2, silicic acid, and Sephadex LH-20; its destruction by dilute HCl and its stability in dilute alkali; its susceptibility to inactivation by aryl sulfatase; and its smooth muscle contracting activity on the guinea pig ileum and the gerbil colon. In vivo selective depletion procedures and in vitro cell isolation procedures were employed to identify the cells responsible for SRS-A production. Mast cells and mixtures of neutrophils and eosinophils produced only very small amounts of SRS-A; this could not be explained by the destruction of preformed SRS-A by these cells. The low yield of SRS-A from mast cells was also not explained by feedback inhibition caused by the histamine they released, because high concentrations of the H2 antagonist, Burimamide, caused only modest increases in SRS-A production by mast cell-containing cell suspensions. Granulocyte-depleted cell suspensions which were derived from thioglycolate-induced mononuclear cell exudates produced more SRS-A per cell than did comparable preparations from uninduced rats. The SRS-A production by induced monocytes was virtually abolished in tandem with the depletion of the phagocytic cells in the preparation. The possible implications of these findings on the source and role of SRS-A in the rat are briefly considered.
Cytotoxic Activities of Normal Cultured Human T Cells
Authors: Alvarez Jose M. , de Landazuri Manuel O. , Bonnard Guy D. , Herberman Ronald B. 
Published: December 2022

Abstract
Normal human T cells grown in continued cultures in medium containing conditioned medium (CM) from PHA-stimulated lymphocytes were studied for their ability to manifest three known forms of cell-mediated cytotoxicity: lectin-induced cellular cytotoxicity (LICC), natural killer cell (NK) activity, and antibody-dependent cellular cytotoxicity (ADCC). The cultured T cells (CTC) were very effective mediators of LICC, being cytotoxic even at very low attacker-target cell ratios in the presence of different lectins, and against different types of targets. When tested without the addition of lectin, the CTC demonstrated a low degree of spontaneous cytotoxicity. This spontaneous cytotoxicity might not be due to conventional NK cells however, since the CTC failed to show significant numbers of cells with Fc receptors (FcR) for IgG, and had no detectable ADCC activity. CTC could represent a population enriched in polyclonal activated T cells with low spontaneous cytotoxicity against a variety of allogeneic target cells, which is greatly enhanced by the addition of lectins during the 51Cr release assay.
Antigen-Specific T Cell-Mediated Suppression
Authors: Pierres Michel , Germain Ronald N. 
Published: December 2022

Abstract
The role of adherent cells (MØ) in 1) primary in vitro PFC responses and 2) in vitro generation of suppressor T cells (Ts) to the antigen L-glutamic acid60-L-alanine30-L-tyrosine10 in responder strain mice has been investigated. Removal of MØ from spleen cell suspensions by either serial culture on plastic surfaces or passage over Sephadex G-10 beads yielded lymphocytes unable to give primary in vitro PFC responses under modified Mishell-Dutton conditions to either soluble GAT or the particulate antigens sheep red blood cells (SRBC) or GAT-complexed electrostatically to methylated bovine serum albumin (GAT-MBSA). However, the viability of such MØ-depleted cultures was significantly lower than control cultures of unseparated spleen cells. Addition of 5 × 10-5 M 2-mercaptoethanol (2-ME) to the culture medium restored viability and permitted nonadherent cells to respond to SRBC and GAT-MBSA, but not to soluble GAT. The response of nonadherent cells to soluble GAT could be restored in the absence of 2-ME by the addition of 1 to 3 × 105 x-irradiated, anti-Thy 1.2 + C-treated peritoneal exudate cells (MØ), or in the presence of 2-ME by 1 to 2 × 104 MØ. This low number of MØ was identical to the number of GAT-bearing MØ necessary in the presence of 2-ME to give optimal GAT PFC responses. Taken together, these data indicate a crucial antigen-presenting role for MØ in primary in vitro anti-GAT responses. Removal of such antigen-presenting cells from responder spleen cells left a lymphocyte population, which, when cultured for 2 days with normally immunogenic (10 µg/ml) concentrations of GAT, gave rise to highly active Thy 1.2+ GAT-specific suppressor cells. This Ts induction was demonstrated in several responder strains. The GAT-Ts were unable to suppress the in vitro responses to SRBC or the copolymer L-glutamic acid50-l-tyrosine50 (GT) as GT-MBSA. Increasing the concentration of GAT to ≥ 30 µg/ml permitted the induction of GAT-Ts in unseparated spleen cells. Thus, in responder mice, MØ able to present antigen in an immunogenic form play a central role in regulating the balance of activated TH and Ts, suggesting that an Ir gene defect in nonresponder mice at the MØ level for this presentation function may account for the predominant suppressor T cell responses of such mice.
Immunoglobulin M Synthesized by Human Lymphoblastoid Cells: Interaction with Staphylococcus Aureus and Protein A
Authors: Howell-Saxton Ernestina , Wettstein Felix O. 
Published: December 2022

Abstract
Immunoglobulin M synthesized by a human lymphoblastoid cell line, LA173, was found to bind specifically to the protein A-bearing Cowan I strain of Staphylococus aureus. The (3H)-leucine-labeled, secreted IgM from these LA173 cells also formed precipitin complexes with purified protein A. Soluble complexes formed at high protein A/IgM ratios retained the ability to bind to the bacterial surface. Precipitin complexes also were observed in double diffusion Ouchterlony gels with a line of identity formed between the IgM, protein A, and anti-IgM in adjacent wells.
Intracellular IgM species from detergent-lysed LA173 cells were bound to S. aureus. Labeled 19S pentamers, 8S monomers, and HL subunits were eluted from the bacteria and identified by velocity sedimentation and SDS agarose-acrylamide gel electrophoresis. In addition, several intermediates migrating between 8S and 19S were detected and shown to contain authentic H and L chains. Binding of the labeled IgM 19S pentamers to staphylococci was not inhibited by prior treatment of the bacteria with an excess of unlabeled human IgG. However, S. aureus saturated with unlabeled IgG did not bind either labeled IgM monomers or labeled IgG. The interaction of this human IgM with S. aureus exhibited a high degree of specificity with quantitative recovery of secreted 19S IgM. Intracellular IgM species were bound selectively by the bacteria with little if any contamination by other cytoplasmic proteins.