bluuebunny/crossref_metadata_2025_split huggingface dataset:
Studies on the mechanism of natural killer cytotoxicity. II. coculture of human PBL with NK-sensitive or resistant cell lines stimulates release of natural killer cytotoxic factors (NKCF) selectively cytotoxic to NK-sensitive target cells.
Authors: Wright S C , Weitzen M L , Kahle R , Granger G A , Bonavida B 
Published: December 2022

Abstract
This investigation has employed the "innocent bystander" type of experimental design to determine whether soluble cytotoxic factor(s) are released during interactions between human peripheral blood lymphocytes (PBL) and NK-sensitive target cells. PBL cocultured with NK-sensitive Molt-4 or K562 target cells in the lower well of a miniaturized Marbrook culture released natural killer cytotoxic factors (NKCF), which diffused across a 0.2-mu Nucleopore membrane and lysed Molt-4 or K562 target cells cultured in the upper chamber. Coculture of PBL with the NK-resistant Raji or WI-L2 cell lines also induced release of NKCF. These factors were selectively cytotoxic to NK-sensitive targets and lysed Molt-4 and, to a lesser extent, K562 cells. However, Raji, WI-L2, and RPMI 1788 cells were all resistant to lysis. In addition, low density fractions from Percoll density gradients that were enriched for NK effector cells also released increased levels of NKCF during coculture with Molt-4 cells. Lysis of Molt-4 and K562 targets was observed after exposure to NKCF for 48 hr and 60 to 70 hr, respectively. Cellfree supernatants containing NKCF were obtained after a short time of incubation (i.e., within 5 hr of coculture of PBL with NK target cells). The factors were nondialyzable, stable at 56 degrees C for 3 hr, and showed partial loss of activity on storage at 4 degrees C or -20 degrees C for 7 days. These data suggest that NKCF may be involved in the lytic mechanism of human NK cell-mediated cytotoxicity.
Early appearance of donor-type antigen-presenting cells in the thymuses of 1200 R radiation-induced bone marrow chimeras correlates with self-recognition of donor I region gene products.
Authors: Longo D L , Davis M L 
Published: December 2022

Abstract
The thymus exerts a potent influence on the development of I region self-recognition and antigen recognition by T cells. The mechanism by which the thymus acts on nascent T cells is unknown. It is assumed, however, that a cell interaction between the developing T cell and an la antigen-bearing cell in the thymus is involved. There are several candidates for the critical thymic cell; thymic epithelial, nurse, and antigen-presenting cells (APC) or dendritic cells. Because thymic epithelial cells derive from the third pharyngeal pouch and thymic APC derive from bone marrow, radiation-induced bone marrow chimeras allow the artificial creation of a chimeric thymus gland in which thymic epithelial cells and APC can be genetically different. We made radiation-induced bone marrow chimeras (F1 leads to P) using supralethal radiation doses (1200 R) and found bone marrow donor- (F1) type APC in the thymuses 3 wk after radiation. When such mice fully reconstitute their immune systems, their T cells behave as donor F1 phenotype T cells. Thus, the I region self-restriction and antigen-recognition repertoire of the T cells correlates with the genotype of the bone marrow-derived thymic APC, not the thymic epithelial cell.
Complexity of the histocompatibility-3 region in the mouse.
Authors: Rammensee H G , Klein J 
Published: December 2022

Abstract
Congenic lines C57BL/10Sn (H-3a), B10.LP-H-3b, B10.C-H-3c, and B10.KR-H-3d were arranged into the 12 possible recipient-donor combinations and immunized. The spleen cells of each recipient were then tested for the presence of cytolytic effector T lymphocytes (CTL) specific for antigenic determinants controlled by the H-3 locus and restricted by class I H-2 loci. The strain-distribution pattern of the determinants defined by the individual CTL was determined by direct testing and by cold-target inhibition analysis. The restriction elements of the individual determinants were identified by the testing of H-2 recombinant strains and by antibody blocking. Five determinants were identified: 1 and 2, restricted by the Db molecule; 3 and 4 restricted by the Kb molecule; and 5, for which the restriction molecule could not be determined. The distribution pattern of determinants 3 and 4 correlated with the distribution of alleles at the beta 2-microglobulin locus. The data could be interpreted as arguing for the existence of three loci in the H-3 complex, with one coding for mutually antithetical determinants 1 and 2, another coding for mutually antithetical determinants 3 and 4, and still another coding for determinant 5.
Suppression of macrophage antimicrobial activity by a tumor cell product.
Authors: Szuro-Sudol A , Murray H W , Nathan C F 
Published: December 2022

Abstract
Medium conditioned by tumor cells (TCM) and certain nonmalignant cells contains a trypsin-sensitive factor that suppresses macrophage oxidative metabolism. Because the killing of intracellular pathogens such as Toxoplasma gondii and Leishmania donovani by macrophages is largely oxygen-dependent, we tested the effect of TCM on the antiprotozoal activity of mouse peritoneal macrophages. After 24 hr of cultivation with TCM, in vivo and in vitro activated macrophages could no longer kill toxoplasmas or inhibit their replication. In vivo administration of TCM resulted in similar impairment. The leishmanicidal activity of resident and activated macrophages, when measured 6 hr after infection, was markedly suppressed by in vitro exposure to TCM. The addition of exogenous H2O2 in the form of glucose-glucose oxidase reconstituted the capacity of TCM-exposed macrophages to kill L. donovani promastigotes as quickly as control cells. Thus, TCM appears to deactivate macrophages by the functional criteria of suppressed antitoxoplasmal and antileishmanial activity, as well as by the biochemical criterion of suppressed oxidative metabolism.
Cells in murine fetal liver and in lymphoid colonies grown from fetal liver can suppress generation of cytotoxic T lymphocytes directed against their self antigens.
Authors: Muraoka S , Miller R G 
Published: December 2022

Abstract
Fetal liver (FL) cells or, in much smaller numbers, cells in lymphoid colonies grown from FL of mouse strain A can suppress the development of cytotoxic activity in a B anti-A mixed lymphocyte reaction (MLR) but not a B anti-C MLR. A, B, and C represent three H-2 different mouse strains. Suppressor cells with similar properties have been described in thymus, bone marrow, lymphoid colonies grown from bone marrow, and athymic nude spleen. They have been referred to collectively as "veto cells". From the point of view of the suppressor cells, a response against self is being suppressed. The FL colony suppressor cells differ from those described in that they can sometimes also suppress an A anti-B response. The FL colony suppressor cells are Thy-1- and resistant to 1500 rad irradiation. These cells may play a role in maintenance of self tolerance. That they are found in FL as early as 13 days of gestation implies that potentially self-reactive cells may develop before experiencing the thymus environment.
Suppressive effect of human natural killer cells on pokeweed mitogen-induced B cell differentiation.
Authors: Arai S , Yamamoto H , Itoh K , Kumagai K 
Published: December 2022

Abstract
The suppressive effect of human natural killer (NK) cells on B cell differentiation induced by pokeweed mitogen (PWM) was investigated. By using Percoll discontinuous density gradient centrifugation, peripheral blood nonphagocytic and nonadherent mononuclear cells were divided into low and high density fractions for which NK cells (Large granular lymphocytes, LGL) and T cells were enriched, respectively. These fractionated mononuclear cells were co-cultured with purified autologous B cells in the presence of PWM, and were examined for their helper and suppressor activities on differentiation of B cells to immunoglobulin-(IgM and IgG) producing cells by a highly sensitive reversed hemolytic plaque assay. The T cell-enriched high density fractions provided help for B cell differentiation to levels higher than that of unfractionated mononuclear cells. On the other hand, the NK-enriched low density fractions did not show helper activity, and when added to the culture of B cells plus helper T cells, they markedly suppressed B cell differentiation. This suppressive activity, as well as the NK cytotoxicity of the NK-enriched fractions, was abrogated by treatment of the cells with monoclonal antibody against human NK cells (HNK-1), but not against T cells (OKT3) in the presence of complement. NK cells also suppressed PWM-driven B cell differentiation in the presence of T4+ (helper/inducer T) but not T8+ (cytotoxic/suppressor T) cells; however, they showed no inhibition of soluble factor-induced B cell differentiation assayed in the absence of helper T cells. It is thus concluded that human peripheral blood NK cells exhibit an ability to suppress PWM-driven B cell differentiation, possibly by acting through the effect on helper T cells but not directly on B cells.
Macrophage-activating factor produced by a T cell hybridoma: physiochemical and biosynthetic resemblance to gamma-interferon.
Authors: Schreiber R D , Pace J L , Russell S W , Altman A , Katz D H 
Published: December 2022

Abstract
Biochemical and biosynthetic evidence has been obtained which indicates that the macrophage activating factor (MAF) produced by the murine T cell hybridoma clone 24/G1, which primes macrophages for nonspecific tumoricidal activity, is a form of gamma-interferon (IFN gamma). MAF and antiviral activities were generated by the clone in proportional amounts under a variety of culture conditions. Production of both activities showed identical dependence on cell density even when production precipitously ceased at cell concentrations greater than 1.2 X 10(6) cells/ml. MAF and antiviral activities displayed identical sensitivities to pH and temperature and were indistinguishable on the basis of binding to insolubilized polynucleotides. Dye-ligand chromatography of a stimulated hybridoma supernatant on a column of Matrex Gel Red A resulted in the 1500-fold purification and 100% recovery of the MAF activity. A qualitatively identical elution profile was also obtained for the antiviral activity; however, only 32% of the original activity was recovered. When subjected to gel filtration on a high performance liquid chromatography system (HPLC), the MAF and antiviral activities present in the Matrex Red pool displayed identical elution profiles and exhibited an apparent m.w. of 50,000. This technique resulted in another 10-fold purification and 50% recovery of the two activities. On HPLC chromatofocusing the MAF activity in the Matrex Red pool could be resolved into seven chromatographically distinct species yet could not be resolved from the antiviral activity on either a qualitative or quantitative basis. These results thus provide quantitative molecular evidence to support the concept that IFN gamma can act as a MAF.
Regulation of the immune response to alloantigens: suppressor and helper T cells generated in the primary MLR of the rat.
Authors: Salomon D R , Cohen D J , Carpenter C B , Milford E L 
Published: December 2022

Abstract
The primary MLR of the rat was used to generate suppressor, cytotoxic, and helper T cells from lymph node cells of the WF (RT1 mu) inbred strain. They were assayed in 51Cr-release cytotoxic assays and by their effect on proliferation of fresh unprimed responder cells. Suppression by MLR cellular products was antigen-specific and generation and functional expression were directed to class II (RT1.B,D) antigens of stimulator cells in the strains tested. In contrast, help was not antigen-specific. The monoclonal antibodies OX8 and W3/25 were used to separate the primed products of the MLR into the constitutive subsets, suppressor/cytotoxic (OX8+) and helper/inducer (W3/25+). Gamma irradiation of OX8+ MLR-primed cells caused modest reductions in suppressive activity, but had no effect on the helper activity of W3/25+ cells. MLR-derived suppressor cells are effective only when added in the early stages of the test primary MLR, whereas helper cells can augment proliferation even when added late. Feedback suppression is not mediated by classical cytotoxic T cells, because of differences in kinetics of development, cell numbers required, susceptibility to freezing, and expression of the RT6 differentiation antigen.
Differentiation of human T lymphocytes. I. Acquisition of a novel human cell surface protein (p80) during normal intrathymic T cell maturation.
Authors: Haynes B F , Harden E A , Telen M J , Hemler M E , Strominger J L , Palker T J , Scearce R M , Eisenbarth G S 
Published: December 2022

Abstract
The thymus is thought to be the primary central lymphoid organ in which T cells mature. Although thymic cortical and medullary compartments are distinct histologically, few antigens have been described that are absolutely acquired during the presumed intrathymic maturation pathway from cortical to medullary thymocytes. In this paper, we describe the acquisition during human intrathymic T cell maturation of a novel protein (p80) defined by a monoclonal antibody (A1G3). Although the p80-A1G3 antigen is distributed throughout the body and is not T cell specific, our study demonstrates that expression of p80-A1G3 antigen in normal human thymus is associated with thymocyte functional maturity and location in the thymus medulla. Moreover, in contrast to other markers of mature human T cells, the p80-A1G3 cell surface protein is not expressed on T6+ cortical thymocytes, and, therefore, is absolutely acquired by medullary thymocytes during T cell maturation. Thus, the p80-A1G3 antigen and the A1G3 antibody provide a heretofore unavailable system for the study of molecular events that transpire during the maturation of thymocytes.
Prevention of cerebral malaria by adoptive transfer of malaria-specific cultured T cells into mice infected with Plasmodium berghei.
Authors: Finley R , Weintraub J , Louis J A , Engers H D , Zubler R , Lambert P H 
Published: December 2022

Abstract
Murine T cell populations specific for Plasmodium berghei parasites were generated in vitro from BALB/c immune lymph node cells. The malaria-specific T lymphocytes were shown: a) to proliferate specifically in vitro in response to stimulation with P. berghei-infected red blood cells; b) to exhibit the Thy-1+, Lyt-1+2- cell surface phenotype; c) to provide specific helper activity for an in vitro anti-hapten (TNP) plaque-forming cell antibody response; and d) to protect P. berghei-infected mice from early mortality due to cerebral malaria.
Production and characterization of monoclonal antibodies to human interleukin 2: strategy and tactics.
Authors: Smith K A , Favata M F , Oroszlan S 
Published: December 2022

Abstract
The unique hormonal characteristics of human interleukin 2 (IL 2), primarily the high affinity of the IL 2-receptor interaction, created several impediments to the generation of monoclonal antibodies to this lymphokine. Because normal cell sources produce only a few micrograms of IL 2 per liter, it was necessary to utilize high producer clones and subclones of a human T leukemia cell line to obtain immunogenic amounts of IL 2 protein. Moreover, assays that required antibody-mediated intervention of the high affinity IL 2-receptor binding were ineffectual in the identification of anti-IL 2-producing hybridomas, thus necessitating the development of immunoassays. Two of three initially derived antibodies detected by enzyme-linked immunoassay were found to react specifically with IL 2 as demonstrated by antibody concentration-dependent neutralization of IL 2 activity. The neutralization of cellular proliferation was specific for IL 2-reactive cells, coincided with an inhibition of IL 2 receptor binding, could be completely overcome by affinity-purified IL 2 and was species-specific; human and murine IL 2 were neutralized, whereas rat IL 2 activity remained unaffected. A third antibody, although much less effective in neutralizing IL 2 activity, bound to IL 2 more avidly and functioned as an efficient immunoabsorbent. IL 2 could be concentrated and purified by immunoabsorption from crude conditioned medium in a single step. The purified product, which retained biologic activity, was made up of a single protein (Mr = 15,500) as determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, reversed-phase liquid chromatography, and amino-terminal amino acid sequence analysis. These results indicate that the distinctive biochemical and functional properties of individual lymphokines may well determine the efficiency with which antibodies may be elicited and detected. However, once produced, anti-lymphokines are uniquely suited for the exploration of the molecular and biologic properties of these immunoregulatory molecules.
Heterogeneity of human mast cells.
Authors: Schulman E S , Kagey-Sobotka A , MacGlashan D W , Adkinson N F , Peters S P , Schleimer R P , Lichtenstein L M 
Published: December 2022

Abstract
Enzymatically dispersed human lung parenchymal cells were fractionated according to size by countercurrent centrifugation elutriation. Human lung mast cells eluted throughout the procedure indicating heterogeneity of mast cell diameters. In seven individual lung elutriations, the mean histamine content ranged from 2.5 +/- 0.5 pg/mast cell for the smallest diameter mast cells (8-10 microns) to 10 +/- 2.5 pg/mast cell for the largest (16-20 microns). Intermediate sized mast cells had correspondingly intermediate histamine contents. The maximum release of histamine after anti-IgE stimulation varied with mast cell size. Small mast cells consistently released less histamine (10 +/- 3.6% net) than the largest diameter mast cells (38 +/- 6% net). This differential histamine release could not be explained by cell surface IgE content which was similar in mast cells of all sizes. The concentration of anti-IgE for maximum histamine release was the same (2 micrograms/ml) for mast cells of all sizes. The generation of PGD2, the predominant cyclooxygenase metabolite of the human lung mast cell, also was correlated positively with mast cell size and to the quantity of histamine released. Studies to date indicate no clear pattern in agonist receptor activities as judged by the inhibition of histamine release by PgE2, the beta-adrenergic agonist, fenoterol, and adenosine. We conclude that human lung mast cells are heterogeneous with regard to size and function.
Activation of human monocyte cytotoxicity by natural and recombinant immune interferon.
Authors: Le J , Prensky W , Yip Y K , Chang Z , Hoffman T , Stevenson H C , Balazs I , Sadlik J R , Vilcek J 
Published: December 2022

Abstract
Human T cell hybridomas were established by fusion of SH9 cells, the 6-thioguanine-resistant mutant line of human T lymphoma Hut 102-B2, with concanavalin A-stimulated human peripheral blood lymphocytes. Hybridoma line L38 produced a macrophage activating factor (MAF) with the ability to activate human peripheral blood monocytes to show enhanced cytotoxicity against human colon adenocarcinoma HT-29 cells in a 72-hr 125iododeoxyuridine-release assay. The L38 line was then cloned by the limiting dilution technique and two sublines, L38B and L38D, were found to produce high levels of MAF constitutively. Interferon activity was also detected in L38B and L38D supernatants. When interferon activity was neutralized with specific antiserum to purified human immune interferon (IFN-gamma), MAF activity was abrogated. To confirm that the MAF activity is indeed due to IFN-gamma, IFN-gamma was purified from the culture supernatant of another human T cell hybridoma, L265K2, a cell line known to produce high levels of IFN-gamma. Two highly purified IFN-gamma fractions with m.w. of 20,000 and 25,000, respectively, were obtained by NaDodSO4/polyacrylamide gel electrophoresis (SDS-PAGE). Similar fractions were obtained from IFN-gamma derived from human peripheral blood lymphocyte (PBL) cultures induced with 12-0-tetradecanoylphorbol-13-acetate (TPA) and phytohemagglutinin (PHA). In comparison, Escherichia coli-derived recombinant human IFN-gamma separated by SDS-PAGE yielded two major active fractions with m.w. of 17,000 and 34,000. With all three types of preparations, a close correlation was found between the presence of IFN-gamma activity demonstrable in an antiviral assay and MAF activity in individual fractions. Substantial quantitative differences were observed in the ability of various human IFN to activate monocytes. Although no MAF activity was detected with IFN-alpha and IFN-beta at concentrations up to 200 U/ml, both natural and recombinant IFN-gamma showed marked MAF activity at concentrations as low as 0.3 to 1 U/ml.
Influence of RU 41.740, a glycoprotein extract from Klebsiella pneumoniae, on the murine immune system. I. T-independent polyclonal B cell activation.
Authors: Wood C D , Möller G 
Published: December 2022

Abstract
A glycoprotein extract from Klebsiella pneumoniae, RU 41.740, has been shown clinically to reduce infectious episodes in patients prone to frequent infections, and experimentally to reduce mortality in animals infected with various bacteria or viruses. The method of action of RU 41.740 in conferring protection from infection is as yet unknown, but in experimental animals, RU 41.740 appears to influence B and T cells as well as macrophages. We report here that RU 41.740 is a strong polyclonal B cell activator and that it activates B cells in a T-independent manner. RU 41.740 also activates spleen cells from the LPS-nonresponder mouse strains, C3H/HeJ and C57BL/10ScCr, which indicates that the polyclonal B cell activating ability of RU 41.740 is not due to contamination by LPS.
Modulation of human B cell immunoglobulin secretion by the C3b component of complement.
Authors: Tsokos G C , Berger M , Balow J E 
Published: December 2022

Abstract
The human C3b component of complement was found to inhibit the differentiation of human B lymphocytes into immunoglobulin-secreting cells in vitro. Pokeweed mitogen (PWM)-induced plaque-forming cell (PFC) responses were inhibited by C3-coated zymosan particles and by purified human C3b. C3b inhibited the PWM-driven responses in a dose-dependent fashion, and it was necessary for C3b to be present in the early phases of the cultures. C3b acted directly on B cells rather than on helper T cells because it inhibited the PFC responses of MNC depleted of T cells and subsequently stimulated with a T cell-independent Epstein Barr virus mitogen. Furthermore, C3b failed to stimulate the generation of suppressor lymphocytes and/or monocytes that might have been responsible for the inhibition of B cell responses. Our results indicate that C3b or its fragments exert negative modulatory effects on human B lymphocyte responses.