bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heterogeneity of EBV-transformable human B lymphocyte populations.
Authors: Chan M A , Stein L D , Dosch H M , Sigal N H 
Published: December 2022

Abstract
Although most human B cells express receptors for Epstein Barr virus (EBV), few (usually less than 1%) are readily transformed into B lymphoblastoid cell lines after exposure to EBV. Transformable cells previously have been found to be mostly resting B lymphocytes. We recently developed a limiting dilution culture system which permits the growth of EBV-transformed B lymphocytes with high efficiency. Because in this system up to over 30% of peripheral blood- or tonsil-derived B cells respond to EBV, we re-examined the properties of EBV-transformable cells. Frequencies of transformable lymphocytes were determined by Poisson analysis. EBV-susceptible B cells committed to IgM, IgG, or IgA secretion were found to occur in the range of 3 to 27, 0.1 to 6, and 0.1 to 5 per 100 B cells, respectively. Under our culture conditions, a major proportion of the IgM-committed cells derived from large lymphocytes which appeared to have entered the cell cycle. This population contains most of the EBV-responsive cells detected and, therefore, most of the additional cells responding in our culture system. In contrast, precursors of IgG- or IgA-producing lymphoblast lines were small cells with DNA contents typical for the G0/G1 phases of the cell cycle. Anti-immunoglobulin antibodies were used in panning experiments to separate B cell subpopulations which expressed different immunoglobulin isotypes on their surface. In limiting dilution cultures of these purified B lymphocytes subsets, it was found that virtually all precursors of IgM-producing cell lines expressed surface IgM (sIgM) before their infection and transformation by EBV. The "cloning efficiency" of positively selected, large sIgM+ cells approached 100%. In contrast, sIgG or sIgA were found only on cells committed to the production of IgG or IgA, respectively. The expression of sIgD was examined by using sequential panning procedures. Virtually all IgM-committed lymphocytes and a subset of cells committed to IgA secretion were found among the sIgD+ cells. The majority of cells committed to IgA production and all IgG-committed cells were found in the sIgD- B cell population. Our findings indicate that the EBV-susceptible B cell subset of normal lymphocytes is heterogeneous with respect to cell size, cell cycle, sIg determinants, and efficiency of transformation. On the basis of our findings and previous reports, we propose a model in which transformability is a B cell-inherent property. Factors unrelated to the virus but present in our culture system appear responsible for the enhanced vulnerability to viral transformation in some cells which entered into the cell cycle.(ABSTRACT TRUNCATED AT 400 WORDS)
Absence of the RT-6 T cell subset in diabetes-prone BB/W rats.
Authors: Greiner D L , Handler E S , Nakano K , Mordes J P , Rossini A A 
Published: December 2022

Abstract
Diabetes-prone Bio-breeding/Worcester (DP) rats exhibit a severe T cell lymphopenia and autoimmune pancreatic insulitis. The present results indicate that the T cell lymphopenia is due in large part, if not entirely, to the absence of the RT-6+ peripheral T cell subset, which includes members of both the helper/inducer (W3/25) and suppressor/cytotoxic (OX 8) antigenic phenotypes. Delineation of the causal mechanism(s) for the selective absence of RT-6+ T cells in DP rats may provide important insights into the cellular basis of the insulin-dependent diabetes mellitus syndrome in these animals.
Anti-hapten IgG antibodies bound to cell surface hapten: anti-IgG antibody prevents dissociation as measured with fluid phase hapten.
Authors: Borsos T , Circolo A , Young-Cooper G O , Mage R 
Published: December 2022

Abstract
We investigated the dissociation by fluid phase hapten of IgG antibodies bound to cell surface hapten in the presence and absence of anti-IgG antibodies. Dissociation was quantitated with fluid phase hapten, preventing reassociation of the anti-hapten antibodies. More than 90% of the anti-hapten IgG alone was prevented from reassociation by low concentrations of fluid phase hapten (nanogram to microgram range). In contrast, no dissociation of some IgG-anti-IgG complexes could be measured even at 24 hr incubation in the presence of very large excess of fluid phase hapten (100 mg/ml). We excluded aggregate formation between anti-hapten antibodies due to cross-linking by anti-antibodies as a cause for decreased dissociability by 1) performing the experiments in large excess of anti-antibody, 2) showing that the phenomenon was independent of anti-hapten antibody density, 3) showing that decreased dissociation also occurred at 4 degrees C, and 4) showing that aggregation by protein A did induce decreased dissociability, albeit three orders of magnitude lower than the anti-antibody. It was concluded that anti-antibody directly affected the "avidity" of cell hapten bound anti-hapten IgG in an unknown manner.
A study of anti-group A streptococcal monoclonal antibodies cross-reactive with myosin.
Authors: Cunningham M W , Hall N K , Krisher K K , Spanier A M 
Published: December 2022

Abstract
Anti-group A streptococcal monoclonal antibodies were obtained from BALB c/BYJ mice immunized with purified membranes from M type 5 Streptococcus pyogenes. Two of the anti-streptococcal monoclonal antibodies were previously shown to cross-react with muscle myosin. In this study the monoclonal antibodies were reacted with tissue sections of normal human heart and skeletal muscle. Antibody binding was estimated by indirect immunofluorescence and immunoperoxidase techniques. Both of the monoclonal antibodies (36.2.2 and 54.2.8) investigated in this report reacted with heart and/or skeletal muscle sections. When evaluated by immunofluorescence, monoclonal antibody 54.2.8 demarcated the periphery of cardiac striated muscle cells and reacted to a lesser degree with subsarcolemmal components. Monoclonal antibody 36.2.2 failed to react with heart sections, but both of the monoclonal antibodies reacted strongly with skeletal muscle sections. Results similar to those observed with indirect immunofluorescence were obtained with the immunoperoxidase technique. By Western immunoblotting and competitive inhibition assays, monoclonal antibodies 36.2.2 and 54.2.8 both were found to react with the heavy chain of skeletal muscle myosin. However, only 54.2.8 reacted with the heavy chain of cardiac myosin. The specificity of the monoclonal antibodies for subfragments of skeletal muscle myosin indicated that monoclonal antibody 36.2.2 was specific for light meromyosin fragments, whereas 54.2.8 reacted with both heavy and light meromyosin. The data demonstrated that two monoclonal antibodies against streptococci were specific for skeletal muscle and/or cardiac myosin and for subfragments of the myosin molecule. The reactions of the monoclonal antibodies with human tissue sections were consistent with the immunochemical reactions of the monoclonal antibodies with both denatured and native myosin.
Expression of CTL-defined, AKR/Gross retrovirus-associated tumor antigens by normal spleen cells: control by Fv-1, H-2, and proviral genes and effect on antiviral CTL generation.
Authors: Green W R 
Published: December 2022

Abstract
In previous studies we have characterized H-2-restricted cytolytic T lymphocytes (CTL) type specific for Gross cell surface antigen-positive tumor cells induced by AKR/Gross leukemia viruses. The generation of such CTL was shown to be controlled by at least three genetic loci including H-2 and Fv-1. The Fv-1n phenotype was able to negate positive immune response gene effects of the H-2b haplotype. Fv-1n-mediated inhibition appeared to operated by allowing the early expression by normal cells of N-ecotropic leukemia virus-related antigens recognized by the antiviral CTL, perhaps via tolerance induction. In the present study, the expression of CTL-defined viral antigens by normal cells is further considered. Possible gene dosage effects by H-2 as well as Fv-1 and the other virus-related (V) genes, including proviral structural loci, were examined by comparison of a panel of congenic and F1 mice. These experiments indicated that the quantitative level of expression of CTL-defined viral antigens was primarily controlled by the Fv-1 genotype. Gene dosage effects were also observed for the V genes and, in some situations, for H-2. The importance of the early display of viral antigens by normal cells was underscored by the inability of those mice to generate specific antiviral CTL responses. Even strains expressing low levels of viral antigens, such as responder X nonresponder (AKR.H-2b:Fv-1b X AKR.H-2b)F1 mice, failed to respond. These results are discussed with respect to the inability of mice of the AKR background to respond with specific antiviral CTL generation and in light of their high incidence of spontaneous leukemia.
Acute toxoplasma infection of mice induces spleen NK cells that are cytotoxic for T. gondii in vitro.
Authors: Hauser W E , Tsai V 
Published: December 2022

Abstract
Murine spleen natural killer (NK) cells from normal and Toxoplasma-infected BALB/c mice were examined for their reactivity against RH strain tachyzoites in vitro. First, the effect of suspending medium on survival of extracellular RH tachyzoites was determined. Optimal parasite viability (by ethidium bromide-acridine orange staining) was observed when tachyzoites were incubated in phosphate-buffered saline (PBS) containing 10% horse serum (HS) for as long as 5 hr. In addition, parasite viability in PBS-HS correlated with subsequent infectivity, because freshly harvested and PBS-HS-incubated tachyzoites were equivalent in their ability to cause lethal infections in normal mice and to survive within normal mouse macrophages. Furthermore, viability and tumoricidal capacity of murine spleen NK cells incubated in PBS-HS was comparable to that of NK cells incubated in a standard cytotoxicity medium. Incubation of effector NK cells and target tachyzoites in PBS-HS in vitro revealed that spleen NK cells from 3-day Toxoplasma-infected mice had significantly greater cytotoxicity for extracellular RH tachyzoites than did control cells from uninfected mice. Moreover, Toxoplasma gondii-induced spleen NK cell toxoplasmacidal activity was significant at all effector to target cell ratios tested, and appeared to be mediated by direct contact between the host cell and the parasite. These in vitro results suggest that NK cells may be important in host defense against T. gondii.
Macrophage cytotoxicity: interleukin 1 as a mediator of tumor cytostasis.
Authors: Lovett D , Kozan B , Hadam M , Resch K , Gemsa D 
Published: December 2022

Abstract
Purified macrophage interleukin 1 (IL 1) induced a concentration-dependent inhibition of the proliferation of two commonly used tumor cell target lines, the human myeloid K562 and the murine T lymphoma Eb. In contrast, mastocytoma-derived P815 cells were not inhibited. The cytostatic action of IL 1 was not associated with direct cytotoxicity and was only partially reversible. PGE or interferon did not appear to mediate these effects. IL 1 treatment of the multipotential K562 cells revealed no morphologic evidence for the induction of specific differentiation. FACS analysis of IL 1-treated K562 cells showed a rapid decrease in transferrin receptor density, and a more delayed, but highly significant, increase in HLA-A,B,C antigen density. These findings provide one explanation for the frequently reported macrophage cytostatic actions against tumor cells, and indicate as well that IL 1, like interferon, may enhance the expression of Class I MHC antigens. These observations further extend the range of IL 1 actions and underscore the fundamental and direct role of this monokine in macrophage antitumor activity.
B cell activation. VII. Independent and synergistic effects of mobilized calcium and diacylglycerol on membrane potential and I-A expression.
Authors: Ransom J T , Cambier J C 
Published: December 2022

Abstract
Although cross-linking of murine B cell membrane Ig (mIg) has been shown to induce a rapid increase in intracellular free calcium [Ca++)i), both the source and the function of the Ca++ in lymphocyte activation is unclear. Toward elucidation of its function, we investigated the relationship between the initial (Ca++)i response and other cell physiologic changes that occur early after mIg cross-linking, apparently as a linear cascade, leading to increased membrane I-A expression. Results suggest that the (Ca++)i response results from polyphosphoinositol hydrolysis induced by mIg cross-linking. The (Ca++)i response cannot be induced by activation of protein kinase C (PKC) with phorbol diesters (e.g., PMA) or synthetic diacylglycerol (DAG), suggesting that this response precedes the PKC activation. However, inhibition of phosphatidylinositol turnover by exposure of cells to dbcAMP during anti-Ig stimulation significantly inhibits the (Ca++)i response, suggesting that phosphatidylinositol turnover may be causally related to Ca++ mobilization. The ability of exogenous phospholipase C to induce the (Ca++)i response also supports this conclusion. Of the products of mono- and poly-phosphatidylinositol hydrolysis, the inositol phosphates (InsP, InsP2, InsP3) are implicated as promoters of Ca++ mobilization, because exogenous synthetic diacylglycerol is without effect on (Ca++)i. In light of recent evidence obtained with other systems, we suggest that InsP3 is responsible for mIg cross-linking-induced Ca++ mobilization from intracellular stores in B lymphocytes. Both depolarization and increased I-A expression are induced by increasing (Ca++)i with the Ca++ ionophores A23187 and ionomycin. These events can also be induced by the activation of PKC with high doses of PMA. When suboptimal doses of both A23187 and PMA are present, these reagents synergize in the induction of depolarization. This suggests that one role for the initial rise in (Ca++)i is to act with the DAG liberated from PtdIns turnover, possibly by enhancing translocation of cytosolic PKC to the plasma membrane, and thereby promote changes in ion transport that are apparent as a decrease in the membrane potential.
Immunotoxins show rapid entry of diphtheria toxin but not ricin via the T3 antigen.
Authors: Youle R J , Uckun F M , Vallera D A , Colombatti M 
Published: December 2022

Abstract
We compared immunotoxins made with ricin and diphtheria toxin (DT) and with two monoclonal antibodies against different T cell-specific antigens, CD5 (T101) and CD3 (UCHT1). Only one reagent, UCHT1 linked to DT (UCHT1-DT), had exceptional properties. UCHT1-DT killed human peripheral T cells and T leukemia cells (Jurkat) at 2 to 10 pM, a concentration 10- to 100-fold lower than UCHT1-ricin and 10 to 500 times lower than native DT. The toxicity was blocked 50- to 100-fold by excess UCHT1 antibody. Human multipotent stem cells were not killed at up to 2000 pM UCHT1-DT. UCHT1-DT shows greater selectivity between T cells and stem cells than UCHT1-ricin, and may better prevent graft-vs-host disease in allogeneic bone marrow transplantation. The kinetics of UCHT1-DT were extremely rapid. UCHT1-DT inhibited Jurkat cell protein synthesis faster than DT and had a different ratio of lag time to inactivation rate. UCHT1-DT killed 90% of Jurkat cells within 2 hr at concentrations nontoxic to human stem cells. In contrast, UCHT1-ricin required more than 18 hr to kill one log of Jurkat cells. Another monoclonal antibody, T101, against the 65 kD CD5 antigen on Jurkat cells was linked to DT and ricin, and was compared with the UCHT1 immunotoxins. UCHT1-DT was 100 times more potent and five to 10 times faster than T101-DT and T101-ricin. Standardization to other antibodies with regard to the number of molecules bound per cell shows that UCHT1-DT is 10 to 100 times faster than previously reported immunotoxins. The role of the T3 antigen in transporting DT to the cytosol is discussed.
Ontogeny of lymphocyte homing receptor expression in the mouse thymus.
Authors: Reichert R A , Jerabek L , Gallatin W M , Butcher E C , Weissman I L 
Published: December 2022

Abstract
The monoclonal antibody MEL-14 has been used in conjunction with immunohistology and multiparameter immunofluorescence to identify and characterize homing receptor-bearing thymocytes at various stages of embryonic and neonatal development. MEL-14hi thymocytes first appear at day 14 of gestation and come to represent about 40% of day 15 fetal thymocytes. Thereafter, the proportion of MEL-14hi thymocytes rapidly declines such that by birth (usually the 20th day of embryonic development) only about 2% of thymocytes are MEL-14hi. Although newborn thymocytes resemble adult thymocytes in this respect, the phenotypic characteristics of fetal and neonatal MEL-14hi thymocytes suggest that this unique subset undergoes a gradual transition from containing exclusively phenotypically immature cells in early gestation to containing predominantly phenotypically mature cells by young adulthood. Thus, virtually none of day 15 MEL-14hi fetal thymocytes are peanut agglutinin (PNA)lo, Ly-1hi, or either Lyt-2-/L3T4+ or Lyt-2+/L3T4-, whereas in the weeks that follow a steadily greater proportion of MEL-14hi thymocytes come to express this mature pattern (roughly 70% at 4 wk of age). Most day 15 MEL-14hi fetal thymocytes appear to express the functional homing receptor molecule, since day 15 fetal thymocytes bind to peripheral lymph node high endothelial venules about 40 to 50% as well as do adult mesenteric node lymphocytes, whereas adult thymocytes bind only about 5% as well. We have also identified a population of outer cortical MEL-14hi Lyt-2-/L3T4- lymphoblasts that appears during thymus regeneration 5 to 6 days after the administration of hydrocortisone. These lymphoblasts express the same phenotype as cells that constitute 40% of the day 15 fetal thymus and only 0.4% of normal adult thymocytes, implying that this particular subset may make up a significant fraction of thymocytes whenever there is a requirement for rapid expansion of the intrathymic and/or peripheral T cell pools. Taken together, these results are consistent with the notion that expression of the MEL-14-defined homing receptor may be closely linked to important intrathymic events that may occur early in T cell development and yet still have an overriding impact on the selection of those thymocytes that will serve as precursors of thymus emigrants.
NK cells suppress the generation of Lyt-2+ cytolytic T cells by suppressing or eliminating dendritic cells.
Authors: Gilbertson S M , Shah P D , Rowley D A 
Published: December 2022

Abstract
Cells highly enriched for natural killer activity suppress the generation of Lyt-2+ cytolytic T cells in one-way mixed lymphocyte cultures. Suppression occurs because natural killer cells suppress or eliminate dendritic cells, which are required for proliferation of both Ly-1+ and Lyt-2+ lymphocytes.
Differential ability of fixed antigen-presenting cells to stimulate nominal antigen-reactive and alloreactive T4 lymphocytes.
Authors: Moreno J , Lipsky P E 
Published: December 2022

Abstract
The capacity of paraformaldehyde-fixed human antigen-presenting cells (APC) to induce responses by autologous, freshly isolated peripheral blood T4 cells was examined and was compared with their ability to stimulate allogeneic T4 cell DNA synthesis. Fixation of glass-adherent cells (AC) with as little as 0.06% paraformaldehyde abolished leucine incorporation, whereas fixation with 0.75% paraformaldehyde caused death of greater than 98% of the AC. Control APC were able to take up and present the soluble antigens streptokinase-streptodornase (SK-SD), tetanus toxoid, or tuberculin-purified protein derivative to autologous Ia-depleted T4 cells. Fixation with greater than 0.06% paraformaldehyde eliminated such ability. When AC were incubated with antigen overnight and were then fixed, however, they were able to present nominal antigen to autologous T4 cells in a genetically restricted manner that was blocked by monoclonal antibodies directed against monomorphic determinants on class II major histocompatibility complex (MHC) molecules. Despite the ability to present nominal antigen, paraformaldehyde-fixed AC were unable to induce allogeneic T4 cell proliferation. Similar results were observed when non-T cells or spleen cells were used as stimulators. The inability of fixed APC to stimulate allogeneic T4 cell DNA synthesis was not reversed by increasing the number of fixed APC or by the addition of control AC autologous to the responding cells. Moreover, interleukins 1 and 2 either alone or in combination also failed to permit maximal T cell proliferation in response to fixed allogeneic APC. The differential effects of fixation on nominal antigen and alloantigen presentation could not be explained by the loss of membrane thymocyte stimulatory activity on fixed AC. These results indicate that antigen-bearing fixed APC are competent to stimulate proliferation by antigen-reactive T4 cells, but are deficient at inducing allogeneic T4 cell DNA synthesis. The differential sensitivity of these two Ia-restricted functions of APC to chemical denaturation (reductive methylation) by paraformaldehyde suggests that the allodeterminants and restriction elements for nominal antigen on MHC class II molecules can be functionally dissociated.
Release of lymphokines after infection with Epstein Barr virus in vitro. II. A monocyte-dependent inhibitor of interleukin 1 downregulates the production of interleukin 2 and interferon-gamma in rheumatoid arthritis.
Authors: Lotz M , Tsoukas C D , Fong S , Dinarello C A , Carson D A , Vaughan J H 
Published: December 2022

Abstract
Epstein Barr virus (EBV)-infection of normal peripheral blood mononuclear cells (PBMC) in vitro induces IFN-alpha secretion from B cell and natural killer (NK) cell populations, and IFN-gamma secretion from T cells. IFN-gamma depends on prior elaboration of IL 2 and IL 1 that originates from monocytes and NK cells. PBMC from rheumatoid arthritis (RA) patients released moderately elevated levels of IFN-alpha (236 +/- 62 U/ml vs 168 +/- 34 in normals). In contrast, IFN-gamma was significantly lower in RA (88 +/- 34 U/ml vs 209 +/- 32) with an associated deficit in IL 2. A monocyte-dependent factor was shown to be responsible for this deficit, since monocyte depletion of RA cultures normalized the levels of IL 2 and IFN-gamma. Significantly lower levels of IL 1 activity were present in the supernatants of RA PBMC cultures as compared with normal cultures, and this was shown to be associated with presence of a nondialyzable IL 1 inhibitor. This inhibitor was capable of preventing the IL 1-dependent synthesis of IL 2 and IFN-gamma by normal PBMC. Exogenous IL 1 or IL 2 restored the deficient IFN-gamma secretion in RA PBMC. Thus, the deficient ability of RA lymphocytes to control EBV infection may be secondary to impairment of a monocyte-T cell interaction at the level of IL 1.