bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of in Vivo and in Vitro Neutrophil Responses to Chemotactic Factors by a Competitive Antagonist
Authors: O'Flaherty Joseph T. , Showell Henry J. , Kreutzer Don L. , Ward Peter A. , Becker Elmer L. 
Published: December 2022

Abstract
Carbobenzoxy-phenylalanyl-methionine (CBZ-Phe-Met) is an inhibitor (antagonist) of the binding to the receptor on polymorphonuclear neutrophils (PMN) for a series of synthetic chemotactic oligopeptides. This inhibitor was studied for its effects on the following chemotactic factor-induced PMN functions: a) chemotaxis, b) granule enzyme release, c) cellular aggregation, and d) in vivo induction of neutropenia. Each of these functions when induced by the chemotactic tripeptides (formyl-methionyl-leucyl-phenylalanine or formyl-methionyl-methionyl-methionine) was inhibited by the antagonist. For each in vitro assay the concentration of antagonist causing a 50% inhibition of response was approximately 10-4 M and the dissociation constant for the antagonist was approximately 10-5 M. Inhibition was dose related, reversible, and competitive. In contrast to these results, the antagonist, CBZ-Phe-Met, did not inhibit any of the four PMN responses induced by the chemotactic fragment of C5. These results further strengthen the relationship between all four chemotactic factor-induced PMN responses and suggest that these chemotactic tripeptides induce each response by interacting with a single receptor. Antagonists of chemotactic factors may represent a new approach to the in vivo suppression of leukotactic factor-mediated biologic responses.
Two Functionally Distinct Subpopulations of Human T Cells That Collaborate in the Generation of Cytotoxic Cells Responsible for Cell-Mediated Lympholysis
Authors: Evans Robert L. , Lazarus Herbert , Penta Ann C. , Schlossman Stuart F. 
Published: December 2022

Abstract
A human thymus-dependent differentiation antigen, TH2 was defined by a rabbit anti-human T cell serum absorbed with autologous B lymphoblasts and leukemic cells bearing T cell markers from a patient with chronic lymphocytic leukemia. Anti-TH2 reacted specifically with thymus-derived lymphoid cells and exhibited two distinct profiles of reactivity with normal peripheral T cells as detected by indirect immunofluorescence on a FACS I. Isolation of strongly reactive, TH2+, from weakly reactive, TH2- T cells by fluorescence-activated cell sorting revealed that the TH2+ subset contained most of the killer activity in cell-mediated lympholysis (CML), but had a diminished response in MLC and a suboptimal or negligible proliferative response to soluble antigens (mumps, PPD, tetanus toxoid). In contrast, the TH2- subset contained markedly less killer activity but amplified cytotoxicity by TH2+ cells and exhibited a proliferative response to both alloantigen and soluble antigens that was often significantly greater than the response by unseparated T cells. The relevance of these findings to previously described human T cell subsets and to functional subpopulations of murine T cells is discussed.
Suppression of the Generation of Human Con A-Induced Cytotoxic Effector Cells by Con A-Activated Suppressor Cells
Authors: Hunninghake Gary W. , Fauci Anthony S. 
Published: December 2022

Abstract
The present study demonstrates that in vitro stimulation by Con A of peripheral blood lymphocytes from certain normal individuals may result in preferential activation of either cytotoxic effector cells capable of killing allogeneic target cells or activation of suppressor cells that prevent the generation of cells cytotoxic to allogeneic targets. Con A-activated lymphoid cells from individuals displaying high levels of cytotoxicity against allogeneic targets (high responders) did not suppress the generation of cytotoxic cells in cell suspensions from other high responders; however, Con A-activated cells from individuals displaying low levels of killing against allogeneic targets (low responders) regularly suppressed the generation of cytotoxic cells in cell suspensions from high responders. Lymphoid cells from low responders suppressed the generation of cytotoxic cells when cocultured in the presence of Con A with cells from a high responder but did not affect the function of killer cells once they had been generated. Pretreatment of cells from a low responder with mitomycin C before co-culturing them in the presence of Con A with lymphoid cells from a high responder impaired their ability to suppress the generation of cytotoxic cells, suggesting that proliferation was necessary for optimal generation of these suppressor cells. In addition, it was demonstrated that Con A-activated cells from low responders were unable to kill an allogeneic target, even when these cells were generated in the presence of a high responder, suggesting that a lack of helper cells was not a sufficient explanation for the inability of cells from low responders to generate killer cells. These studies provide further evidence that suppressor cell functions of subpopulation of lymphoid cells play an important role in the regulation of immune responses of normal individuals.
Linkage between a Gene for a Serum Protein and the Gene for the Ig Kappa Light Chain in Rabbits
Authors: Usher David C. , Mayer Eugene P. , Dray Sheldon , Reiter Harvard 
Published: December 2022

Abstract
A rabbit serum protein (Prt) that migrates ahead of transferrin in polyacrylamide gel electrophoresis is inherited in a simple Mendelian fashion. The gene for this protein is linked to the gene for the Ig κ light chain and the degree of linkage is calculated as 23.5 ± 4.7 centimorgans.
Partial Purification and Molecular Characterization of a Lymphokine (Costimulator) Required for the Mitogenic Response of Mouse Thymocytes in Vitro
Authors: Shaw Jennifer , Monticone Vicky , Paetkau Verner 
Published: December 2022

Abstract
We have partially purified a lymphokine, costimulator, which is necessary to induce mitogenesis in mouse thymocytes in vitro. Costimulator is released from mouse leukocytes exposed to Con A for 12 to 18 hr. It has been purified more than 100 X by gel exclusion chromatography and isoelectric focusing. Thymocytes from CBA/J mice respond to the mitogenic lectin Con A only if the costimulator concentration is above a certain level. Culturing such cells with Con A at a density below 1 × 106 cells/ml produces costimulator concentrations too low for mitogenesis. This system has been developed into a quantitative assay for costimulator, to monitor purification, recovery, and biologic activity in various methods of molecular characterization. The activity is trypsin sensitive, and has a buoyant density characteristic of protein or glycoprotein. However, for a protein, it is relatively heat stable. Its m.w., established by carrying out sedimentation, gel filtration, and buoyant density measurements, is 30,500, and its frictional coefficient is 1.45. Costimulator purified by isoelectric focusing is active at 10-10 M or lower in tissue culture.
The Response to Mitogens and Allogeneic Cells of Human Lymphocyte Subpopulations Separated by Their Differential Binding to Monolayers of Bacteria
Authors: Kleinman Raphael , Teodorescu Marius 
Published: December 2022

Abstract
Various strains of bacteria were previously shown to bind to different lymphocyte subpopulations, i.e., to B cells and to four T cell subpopulations (T1, T2, T3, T4, our classification). We prepared bacterial monolayers and used them to separate lymphocyte subpopulations according to their binding properties. Bacteria were coupled to glutaraldehyde-treated gelatin layers and were subsequently fixed with formaldehyde. Suspensions of peripheral blood lymphocytes (PBL) were centrifuged against the bacterial monolayers and the cells that did not attach were resuspended with the help of a rocking platform. The percentage of PBL that remained attached was similar to the expected values according to the percentage of PBL-binding bacteria in a “rosette formation” assay. The cells that did not adhere to Escherichia coli-0 monolayers, i.e., practically all PBL, responded to the same extent as the unseparated PBL to four mitogens: phytohemagglutinin, concanavalin A, pokeweed mitogen, and streptolysin 0-associated mitogen. The lymphocytes that did not adhere to E. coli-2 monolayers, namely the T3T4 cells, responded poorly to all four mitogens. Also, the response to various doses of concanavalin A of T3T4 cells was much lower than that of purified T cells. The poor response of T3T4 cells was not due to the reduction in viability or to monocyte depletion. Moreover, the T3T4 cells responded in one-way mixed lymphocyte reactions as well as the unseparated PBL. We concluded that T3T4 lymphocytes could be separated by adherence to bacterial monolayers and that they may be functionally different from the other lymphocyte subpopulations identified by binding of bacteria.
Studies on the Question of Conventional Immunoglobulin on Thymocytes from Primitive Vertebrates
Authors: Yamaga Karen M. , Kubo Ralph T. , Etlinger Howard M. 
Published: December 2022

Abstract
An unexpected cross-reactivity between trout immunoglobulin (Ig) and keyhole limpet hemocyanin (KLH) was observed. Rabbit antisera to KLH were capable of binding to radioiodinated trout Ig and, conversely, antitrout Ig reacted with KLH. The cross-reactive antibodies were not found in preimmune sera and did not arise because of a common contaminant in the two immunizing preparations. The molecular basis of the cross-reactivity was found to reside in the carbohydrate moieties. Isolated glycopeptides from KLH and trout Ig were efficient inhibitors of the croos-reactivity. Furthermore, l-fucose was capable of inhibiting the cross-reactivity, whereas other monosaccharides tested did not. Absorption of anti-KLH with trout Ig and anti-trout Ig with KLH effectively removed the cross-reactive antibodies and only slightly affected the titer to their respective homologous antigens. Antibodies with specificity for l-fucose were isolated from anti-KLH and anti-trout Ig sera by passage over affinity columns and elution with the monosaccharide.
Fc-Receptor Heterogeneity of Human Suppressor T Cells
Authors: Hayward Anthony R. , Layward Lorna , Lydyard Peter M. , Moretta Lorenzo , Dagg Martha , Lawton Alexander R. 
Published: December 2022

Abstract
Concanavalin A (Con A) stimulated the IgM-binding subpopulation of human T cells (TM) to suppress the pokeweed mitogen-induced differentiation of B lymphocytes to plasma cells.
Control TM cells that had not been Con A activated did not suppress. The degree of suppression was related to the number of Con A-TM cells added to the cultures and it was abolished by irradiation of the T lymphocytes either before or after the 24-hr culture period with Con A. Suppression did not require the presence of TG cells, whose suppressor potential has been previously established. These findings indicate that suppressor activity is not confined to the TG subpopulation but may be expressed by TM cells also.
Molecular Heterogeneity of Secretory IgA Anti-DNP Antibodies
Authors: Montgomery Paul C. , Skandera Cheryl A. 
Published: December 2022

Abstract
Evidence is presented that demonstrates that the microscale sucrose isoelectric focusing technique can be used to assess the molecular heterogeneity of secretory IgA anti-DNP antibodies. The data indicate that substitution of the DNP group on the bacterial carrier, pneumococcus, can limit the structural complexity of secretory IgA anti-DNP antibodies. The data support the concept that factors governing secretory IgA antibody heterogeneity are analogous to those influencing the heterogeneity of serum IgG antibodies.
Independent Stimulation of Motility and the Oxidative Metabolic Burst of Human Polymorphonuclear Leukocytes
Authors: Bass David A. , Dechatelet Lawrence R. , Mccall Charles E. 
Published: December 2022

Abstract
It has recently been suggested that a single stimulus to the membrane of the polymorphonuclear neutrophil leukocyte (PMN) produces a sequential, stereotyped response involving motility, degranulation, and the oxidative metabolic burst, and conversely, that the chemotactic response is dependent upon the stimulation of the hexose monophosphate shunt (HMPS). We have used small, synthetic substances, known to cause either increased motility or the metabolic burst, to examine whether these events can be stimulated independently. Phorbol myristate acetate (PMA) is a surface active agent that causes marked stimulation of iodination, superoxide production, chemiluminescence, and the HMPS. Such stimulation by PMA did not alter random or directional motility of PMN in the chemotaxis-under-agarose assay. Also, preincubation of PMN with PMA did not deplete their energy source for chemotaxis as demonstrated by a normal chemotactic response to zymosan activated serum. N-formylmethionyl peptides (f-met-phe, f-met-leu-phe) caused a dose-related stimulation of random and directional motility of PMN, but only a very slight stimulation of the HMPS, protein iodination, superoxide production, or chemiluminescence, and this minimal response occurred at more than 1000 times the concentration needed for stimulation of motility. These results indicate that stimulation of motility in the metabolic burst may involve separate events at the membrane of the PMN and that the events are not necessarily interdependent.
Human Cytotoxic Response in Vitro to Trinitrophenyl-Modified Autologous Cells
Authors: Shaw Stephen , Shearer Gene M. 
Published: December 2022

Abstract
The present study is a survey of classes of self determinants that are recognized in association with the trinitrophenyl hapten (TNP) by human T cell effectors sensitized in vitro with TNP-modified autologous cells. Specificity was investigated by studies of direct lysis and cold target cell competition. Interpretation of the results of direct lysis experiments was facilitated by the use of interaction analysis. Studies of effector populations from six siblings demonstrated that on the average approximately 40% of the cytotoxic activity was specific for polymorphic determinants of which most or all were HLA linked. Studies of effectors from six unrelated donors, selectively matched for HLA-A and -B locus determinants, demonstrated that some of the cytotoxic activity was directed against HLA-A and/or -B locus-associated polymorphic determinants, but that the serologically-defined HLA-A and -B locus antigens were not the only polymorphic determinants recognized. Studies by cold target cell competition demonstrated that some of the cytotoxic activity was directed against TNP in association with relatively nonpolymorphic antigens. Thus, there was evidence for considerable diversity of the classes of self determinants that human T cells can recognize in association with TNP. Furthermore, the possibility of immune response gene control of the cytotoxic response to these determinants was suggested by differences between donors in their response to TNP-modified self determinants.
Measurement of Antigen-Specific IgG Autoantibody Production in Vitro
Authors: Eilat Dan , Reeves J. Patton , Steinberg Alfred D. , Schechter Alan N. 
Published: December 2022

Abstract
This report describes the development of a direct, highly sensitive and reproducible microassay for measuring picogram amounts of IgG antibody produced in spleen cultures of NZB/NZW female mice and specific for a well defined nucleic acid antigen (native ssRNA). The spontaneously synthesized antibodies were extensively purified from the culture supernatants. The isolated IgG anti-RNA antibodies had a high affinity, limited heterogeneity, and were specific for RNA as compared with DNA. Spleen cell cultures produced quantities of anti-RNA antibodies sufficient to account for a large proportion of the circulating anti-RNA antibodies in the whole animal. However, our results provide no evidence for the recently published suggestion (Sawada et al., 1977. J. Immunol. 119:355) that autoreactive lymphocytes are released from normal immunoregulatory control during in vitro culture conditions.
The Expression of Ia Antigens on Immunocompetent Cells in the Guinea Pig
Authors: Yamashita Uki , Shevach Ethan M. , Thomas David W. 
Published: December 2022

Abstract
In the present study we examined the expression of I-region-associated (Ia) antigens by guinea pig T lymphocytes stimulated in vitro with antigen-pulsed macrophages. Treatment of lymph node (LNL) or peritoneal exudate (PEL) T cells taken directly from immune animals with anti-Ia serum and complement (C) dramatically reduced their proliferative response to antigen-pulsed macrophages when determined on the 4th day of culture. In contrast, the response of immune T cells that had been selected by culture for a week with antigen-pulsed macrophages and restimulated in a second culture was not affected by anti-Ia and C treatment. This same result occurred with selected LNL or PEL that were initially treated before the selection culture with either normal serum or anti-Ia serum and C. LNL became resistant to anti-Ia serum and C treatment by 3 days of culture whereas antigen-specific PEL were still sensitive at that time. These results indicate that in an immune animal two antigen-specific T cell subpopulations are generated based on their sensitivity to anti-Ia serum and C treatment, but that only the resistant population is selected by in vitro culture. In addition, we demonstrated that the Ia-negative T cell population can only be activated by histocompatible antigen-pulsed macrophages.
Nonspecific Suppressive and Cytostatic Activities Mediated by Human Colonic Carcinoma Tissue or Cultured Cell Extract
Authors: Remacle-Bonnet Maryse M. , Pommier Gilbert J. , Luc Chantal , Rance Roselyne J. , Depieds Raymond C. 
Published: December 2022

Abstract
We have previously shown that soluble extracts from human colonic carcinoma (SCE) were potent inhibitors of the PHA-induced DNA synthesis of normal allogeneic peripheral lymphocytes. From the present study, SCE appeared to have a broad and nonspecific range of activity. The SCE-suppressive effect was observed whatever the lymphoid organ or the animal species used as a source of stimulated lymphocytes. Moreover, we always obtained a complete inhibition of the lymphoproliferative response to all tested mitogens including PHA, Con A, PWM, and, for animal lymphocytes, LPS. In addition to the suppressive activity on lymphocytes, SCE also inhibited proliferation of cultured human CCL6 embryonic intestine cells and HT29 colonic carcinoma cells, and of cultured rat fibrosarcoma cells.
Soluble extracts from HT29 cells (SCCE) were able to mimic the nonspecific suppressive and cytostatic activities of SCE. The suppressive activity was also found in extracts from hepatic metastases (SHME) of a primary colonic tumor. In contrast, soluble extracts from normal liver or nonmalignant colonic mucosa did not interfere with cell proliferation.
These data suggest that both SCE and SCCE contain molecular components(s) that can inhibit a wide variety of proliferating cells, including stimulated lymphocytes.
Biosynthesis of Immunoglobulin in Human Immunoproliferative Diseases
Authors: Hammerton Kerie , Cooper David A. , Duckett Margaret , Penny Ronald 
Published: December 2022

Abstract
The kinetics of synthesis and secretion of immunoglobulin by bone marrow cells from 32 patients with multiple myeloma (17 IgG, 8 IgA, 7 Bence Jones only) and two patients with benign monoclonal gammopathy have been compared. Optimal conditions have been defined for quantitatively measuring the incorporation of radioactive leucine into intracellular and secreted protein and immunoglobulin.
In cells continuously labeled with [3H]-leucine the rate of protein synthesis in the intracellular lysate was constant over the 24-hr-culture period. The amount of labeled intracellular immunoglobulin increased linearly during the initial 2 to 4 hr and then remained constant, indicating saturation of the intracellular pool of immunoglobulin. Labeled protein and immunoglobulin were secreted linearly after an initial lag phase of 2 to 8 hr. The major part of the secreted protein was identified as the myeloma protein and was proportional to the percentage of myeloma cells in culture; this was particularly the case for IgG and Bence Jones myeloma patients. By linear regression analysis the amount of myeloma protein secreted by the cells was directly proportional to the amount synthesized within the cell and in addition correlated with the synthesis and secretion of total protein. These neoplastic plasma cells synthesize and secrete myeloma protein as a major product and appear to be comparable to normal antibody-producing plasma cells.
In Vitro Activation of Suppressor Cells from Spleens of Mice Treated with Radioactive Strontium
Authors: Merluzzi Vincent J. , Levy Elinor M. , Kumar Vinay , Bennett Michael , Cooperband Sidney R. 
Published: December 2022

Abstract
Mice were treated with two 100-µCi injections of 89Sr to deplete marrow-dependent (M) cells. Mice so treated responded normally to immunization with sheep red blood cells (SRBC) in vivo; moreover, spleen cells from 89Sr-treated mice were able to respond to SRBC after infusion into irradiated recipient mice. However, spleen cells from mice treated with 89Sr did not respond to SRBC in vitro and mixtures of normal spleen cells with the latter were also not able to respond in vitro. The discrepancy between in vivo and in vitro responses was abolished by culturing spleen cells for 24 hr before testing their ability to respond to SRBC in the adoptive transfer in vivo. Pretreatment of spleen cells from 89Sr-treated mice with 1000 R of γ-radiation lessened their suppressive activity. The suppressor cells were detected in spleens of athymic nude mice treated with 89Sr. The suppressive activity, after the 24-hr culture period, was not abolished by irradiation and was active in vivo as well as in vitro. Thus, depletion of M cells by 89Sr results in the appearance within the spleen of thymus-independent suppressor cells, which require a short period of in vitro cultivation before becoming functionally active.
Cell-Mediated Cytotoxicity Against Virus-Infected Target Cells in Humans
Authors: Santoli Daniela , Trinchieri Giorgio , Lief Florence S. 
Published: December 2022

Abstract
In a 51Chromium release assay performed without immune sera, purified lymphocytes from randomly selected healthy donors killed significantly more allogeneic virus-infected than noninfected fibroblasts. An incubation period of 18 to 20 hr was optimal for determining cytotoxicity, but increased cytotoxic activity against infected cells was observed as early as 6 hr from the start of the test. No correlation could be found between donors' antibody titers to any virus tested and the cytotoxic efficiency of their effector cells: virus-infected cells were lysed by both seropositive and seronegative individuals. With several different cell fractionation techniques, the effector cell in this system could not be distinguished from the human natural killer cell, which is a lymphocyte with receptors for the Fc fragment of IgG but with no surface immunoglobulin. When lymphocytes were separated on the basis of ability to form rosettes with neuraminidase or AET (2-aminoethylisothiouronium bromide hydrobromide)-treated sheep erythrocytes, the majority of cytotoxic activity was consistently recovered in the nonrosetting fraction. A portion of it, however, was always present in the rosetting fraction and was, again, mediated by lymphocytes carrying receptors for the Fc fragment of IgG.