bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of interferon-gamma on proto-oncogene expression during induction of human monocytic differentiation.
Authors: Sariban E , Mitchell T , Griffin J , Kufe D W 
Published: December 2022

Abstract
Activation of the proto-oncogenes c-fos, c-fms, and c-sis has been associated with monocytic differentiation. In the present study, we monitored the relationship of c-myc, c-fos, c-fms, and c-sis expression to interferon-gamma (IFN-gamma)-induced monocytic differentiation of human HL-60 promyelocytic leukemia cells. Treatment of HL-60 cells with 500 U/ml IFN-gamma arrested cell proliferation after 3 days. Appearance of the monocytic phenotype was manifested within 24 hr of IFN-gamma exposure by: increased nitroblue tetrazolium reduction; increased cell surface expression of the HLA-DR, Mo1, and MY4 antigens; and induction of transcripts for the second component of complement (C2) and tumor necrosis factor. In contrast, c-myc expression decreased as a later event after 72 hr of IFN-gamma exposure, and c-fos transcripts remained undetectable until 5 days of treatment. Furthermore, c-fms RNA and transcripts for the macrophage marker apolipoprotein E were induced only after 7 days. Finally, expression of the c-sis proto-oncogene at the RNA and protein levels remained undetectable after induction with IFN-gamma. These findings would thus suggest that declines in c-myc RNA, as well as induction of c-fos, c-fms, and c-sis expression, are not requisite events in the commitment of HL-60 cells to IFN-gamma-induced monocytic differentiation. Expression of c-fos and c-fms, however, is associated with acquisition of markers associated with maturation to macrophages.
Development of a cell with dendritic morphology from a precursor of B lymphocyte lineage.
Authors: Corradi M P , Jelinek D F , Ramberg J E , Lipsky P E 
Published: December 2022

Abstract
Cells developing dendritic morphology were detected in cultures of highly purified human B cells incubated with 4 beta-phorbol 12-myristate 13-acetate (PMA). After 72 hr of culture, 2 to 7% of the cells had assumed a dendritic shape provided that contact with a plastic or glass surface also occurred. Dendritic cells developed in cultures of B cells prepared by positively selecting cells that stained with the B cell-specific monoclonal antibody B1 with the fluorescence-activated cell sorter. By contrast, dendritic cells could not be detected in cultures of cells obtained from patients with Bruton's type agammaglobulinemia that lacked B cells. Cells with dendritic morphology were nonspecific esterase negative and not phagocytic. They expressed HLA-DR, DQ, and DP antigens, receptors for interleukin 2 and transferrin, and were stained by B1 and 60.3, an antibody that identifies the beta-chain common to lymphocyte function associated antigen-1, complement receptor 3, and the p150,95 antigen, but not by monoclonal antibodies to monocytes, complement receptors 2 or 3, NK cells, T cells, or Langerhans' cells. Formation of dendritic cells was inhibited by microtubule poisons (vinblastine, colchicine), a microfilament inhibitor (cytochalasin B), and the 60.3 monoclonal antibody, but not by inhibition of DNA synthesis. These data indicate that a subset of B cells is capable of assuming dendritic morphology after stimulation with phorbol esters and attachment to a surface. These dendritic cells exhibit characteristics that are quite similar to the interdigitating cells found in T cell-dependent areas of lymph nodes.
Effects of monoclonal anti-H-2Ld and anti-H-2Dd alloantibodies in the immunological enhancement of skin grafts and neonatal heart grafts in the mouse.
Authors: Lems S P , Jacobs C W , Capel P J , Koene R A 
Published: December 2022

Abstract
Three anti-H-2Ld and two anti-H-2Dd monoclonal alloantibodies were analyzed for their capacity to enhance skin graft and neonatal heart graft survival. Of two anti-H-2Ld antibodies with the same specificity but with different isotypes, IgG2a antibody 30-5-7S prolonged graft survival in a skin graft combination with an Ld difference, whereas IgM antibodies did not. A second IgG2a antibody, but with a specificity different from 30-5-7S, was ineffective on its own. However, when mixed with 30-5-7S, skin graft survival was augmented as compared with the prolongation by 30-5-7S alone. Enhancement by anti-H-2Ld antibodies was dependent on the extent of the H-2 graft barrier. It was abrogated on extension of the graft barrier to a D-end H-2 difference by using the B10.A----B10.BR combination. Also, anti-Dd antibodies, either alone or in combination with anti-Ld, were ineffective in this skin graft combination. By using the same graft combination but the less immunogenic neonatal heart graft model, anti-Ld antibodies were still ineffective, but both anti-Dd antibodies were able to enhance graft survival from 15 to 22 days. When mixed with anti-Ld antibody 30-5-7S, graft survival was augmented further to 30 days. These results indicate that two kinds of enhancing alloantibodies may be distinguished. One category interacts with immunodominant epitopes on H-2 molecules, but their effectiveness may be limited to a particular H-2 difference, because immunodominance may vary from one graft barrier to another. In the second category, antibodies are ineffective on their own but they are able to potentiate the effects of antibodies of the first kind. These allocations are relative, however, because they are dependent on the type of graft examined.
Mechanisms of T cell hyperreactivity in obese strain (OS) chickens with spontaneous autoimmune thyroiditis: lack in nonspecific suppression is due to a primary adherent cell defect.
Authors: Krömer G , Schauenstein K , Dietrich H , Fässler R , Wick G 
Published: December 2022

Abstract
The disturbed homeostasis of the immune system in Obese strain (OS) chickens with spontaneous autoimmune thyroiditis consists in a general T cell hyperreactivity (concanavalin A hyperresponsiveness, interleukin 2 (IL 2) hypersecretion), particularly expressed by those lymphocytes which infiltrate the diseased thyroid gland. This abnormality has been attributed to a defective regulation of both IL 2 production and IL 2 function by low m.w. factors, which are present in serum and splenocyte culture supernatants of normal chickens, but deficient in the OS. In the present study we identified the cellular origin of IL 2 antagonistic activity as a nonlymphoid, adherent cell. Suppressor factor production in vitro was confined to the plastic adherent fraction of spleen cells and preincubation of splenocytes with nylon wool, silica particles, or carbonyl iron significantly reduced the nonspecific suppressive activity of the culture supernatant. Kinetic studies revealed the defect in nonspecific suppression to entail prolonged IL 2 production by concanavalin A-activated OS spleen cells. In vivo treatment of normal White Leghorn chickens with silica led to a decrease in suppressive serum activity down to the OS level, whereas neither neonatal thymectomy nor bursectomy had any effect. The defective suppressor factor production in autoimmune chickens appeared to be due to a functional, but not numeric defect of macrophages as revealed by phenol red staining. The possibility that this aberration in adherent cell function might be a secondary phenomenon to the recently described reduced corticosterone tonus in OS chickens was excluded by in vivo substitution with exogenous glucocorticoids which did not normalize the suppressor defect in serum or in conditioned medium. Finally, we present evidence that T lymphoblasts from OS animals are less susceptible to IL 2 antagonistic regulation than normal cells, which possibly further contributes to the T cell hyperfunction of this autoimmune strain.
Induction of membrane-associated interleukin 1 by tumor necrosis factor in human fibroblasts.
Authors: Le J M , Weinstein D , Gubler U , Vilcek J 
Published: December 2022

Abstract
Highly purified recombinant human tumor necrosis factor (TNF) was found to induce interleukin 1 (IL 1) production in diploid human FS-4 fibroblasts. Demonstration of IL 1 activity was based on the ability of TNF-treated FS-4 cells, subsequently fixed with formaldehyde, to stimulate thymocyte proliferation in the presence of phytohemagglutinin. Incubation of FS-4 cells with the optimal dose of TNF (10 ng/ml) resulted in a marked increase in [3H] thymidine uptake by thymocytes co-cultured with formaldehyde-fixed FS-4 cells. Induction of this apparently membrane-associated IL 1 (MA-IL 1) activity was demonstrable at 6 hr and reached a plateau after 48 hr of incubation with TNF. FS-4 cells did not secrete soluble IL 1 in response to TNF. Dexamethasone suppressed the synthesis of TNF-induced MA-IL 1. A monoclonal antibody specific for TNF neutralized MA-IL 1 induction, indicating that the induction is due to TNF, and not to a contaminant in the TNF preparation. The ability of TNF to induce IL 1 synthesis in FS-4 fibroblasts at the transcriptional level was confirmed by S1 nuclease protection assay. Cytoplasmic RNA from uninduced FS-4 cells contained no demonstrable RNA hybridizing with a human IL 1-alpha cDNA probe and low levels of RNA hybridizing with an IL 1-beta cDNA. Induction with TNF resulted in the appearance of IL 1-alpha mRNA and a very significant increase in IL 1-beta mRNA, indicating that TNF induces the synthesis of both IL 1-alpha and IL 1-beta in FS-4 cells.
Normal human sera contain antibodies directed at Fab of IgA.
Authors: Jackson S , Montgomery R I , Mestecky J , Czerkinsky C 
Published: December 2022

Abstract
Serum samples from 26 normal volunteers were evaluated by isotype-specific ELISA for the presence of IgG and IgM antibodies directed at IgA. Although there were wide variations in antibody levels, anti-IgA antibodies of both isotypes were found in all individuals tested. The anti-IgA activity was detected against a variety of polymeric and monomeric IgA1 and IgA2 myeloma proteins containing both kappa and lambda light chains. By using Fab and Fc fragments generated by incubation of an IgA1 myeloma protein with IgA1 protease, it was shown that the anti-IgA activity was specific for the Fab portion of the IgA molecule. It was also demonstrated that the serum of two individuals contained both IgG and IgM activity directed at autologous affinity-purified IgA. IgM antibody levels against both whole IgA and Fab of IgA were significantly higher than IgG antibody levels. Cells producing anti-IgA antibodies of both isotypes were detected in lipopolysaccharide-stimulated human spleen.
In vitro T cell-mediated killing of Pseudomonas aeruginosa. V. Generation of bactericidal T cells in nonresponder mice.
Authors: Powderly W G , Pier G B , Markham R B 
Published: December 2022

Abstract
We have previously reported that BALB/c mice immunized with 10 micrograms of a Pseudomonas aeruginosa polysaccharide antigen (PS) and 100 micrograms vinblastine sulfate develop T cell-mediated protective immunity, but fail to generate an antibody response. Vinblastine functions in this system to remove a suppressor cell that normally inhibits expression of this form of immunity after PS immunization. T cells from CB.20 mice immunized with the 10 micrograms of PS and 100 micrograms vinblastine fail to kill P. aeruginosa in vitro. These mice are allotype congenic with BALB/c mice, differing at loci closely linked to the IgH-1 locus. Immunization of CB.20 mice with 10 micrograms PS and 100 micrograms vinblastine results in the appearance of T cells which suppress in vitro bactericidal activity of BALB/c T cells. In the current study we found that T cell-mediated bactericidal activity can be generated in CB.20 mice by increasing the dose of vinblastine given at the time of PS immunization. The phenotype of the CB.20 bactericidal T cell generated by high dose vinblastine is identical to that of the BALB/c bactericidal T cell, and the CB.20 bactericidal T cell can adoptively transfer protective immunity to granulocytopenic mice. After immunization of BALB/c and CB.20 mice with PS alone, approximately one log fewer CB.20 T cells than BALB/c T cells are required to suppress bacterial killing in vitro. Furthermore, the number of CB.20 T cells required to suppress in vitro bacterial killing is directly correlated with the dose of vinblastine administered at the time of immunization. Increasing the immunizing dose of PS overcomes suppressor activity and allows the generation of bactericidal T cells in BALB/c mice without a requirement for vinblastine. CB.20 mice fail to generate bactericidal T cells after immunization with high doses of PS. These results indicate that CB.20 and BALB/c mice both possess the full repertoire of T cells required to express bactericidal T cell activity and that the differences in their responses reflect only quantitative differences in suppressor cell activity.
Selective inhibition of 28S ribosomal RNA in macrophages activated by interferon-gamma or -beta.
Authors: Varesio L , Clayton M , Radzioch D , Bonvini E 
Published: December 2022

Abstract
We have investigated the metabolism of RNA in mouse peritoneal exudate macrophages activated by interferon (IFN)-gamma or -beta. Both species of IFN induce cytotoxic activity in macrophages. We observed a decrease in the incorporation of [3H]-uridine into total RNA in macrophages treated with doses of IFN that induce cytotoxic activity. IFN-gamma was 100-fold to 1000-fold more potent that IFN-beta in inhibiting RNA synthesis. [3H]Uridine-labeled RNA was purified from IFN-activated and control macrophages and was size fractionated on agarose gels. Macrophages activated by either IFN-gamma or IFN-beta had an imbalanced accumulation of 28S ribosomal RNA compared with their accumulation of 18S ribosomal RNA. Pulse-chase experiments suggested that IFN induced a selective inhibition of the processing of 28S ribosomal RNA. These results provide the first evidence that IFN can modulate ribosomal gene expression at the post-transcriptional level. Moreover, they indicate that inhibition of 28S ribosomal RNA accumulation in macrophages is a molecular event triggered by IFN-gamma, as well as IFN-beta.
The role of the T cell receptor, CD8, and LFA-1 in different stages of the cytolytic reaction mediated by alloreactive T lymphocyte clones.
Authors: Blanchard D , van Els C , Borst J , Carrel S , Boylston A , de Vries J E , Spits H 
Published: December 2022

Abstract
The cytotoxic reaction mediated by cytotoxic T lymphocytes (CTL) consists of three phases: first, the CTL binds to the target cell; next, the CTL is triggered to lyse the target cell; and in the third phase, the CTL detaches from the target cell which is lysed in the absence of the CTL. Recently, we obtained evidence that human alloreactive CTL clones initially adhere to target cells without the involvement of the interaction between the T cell receptor (Tcr) and its specific target antigen. In the present study, we investigated the effect of monoclonal antibodies specific for the Tcr on the cytotoxic reaction of three CD8+ HLA-A2-specific CTL clones, using a single cell assay in which the binding event can be distinguished from the post-binding (lytic) phase of the cytolytic reaction. It was found that monoclonal antibodies directed at a variable part of the Tcr do not affect the binding phase but strongly block the lytic phase of the cytotoxic reaction. An anti-constant region Tcr antibody and an anti-CD3 reagent had a similar effect on the two phases of the reaction as the anti-variable part Tcr antibodies. In contrast, antibodies specific for LFA-1 strongly blocked the adhesion phase but did not affect the lytic phase. Antibodies specific for CD-8 had intermediate effects. They could block both the adhesion as well as the lytic phase. The effect of anti-CD8 appeared to be dependent on the CTL clone tested. One clone was found to be inhibited in the adhesion phase, but not in the lytic phase, whereas anti-CD8 hardly blocked the adhesion phase of two other CTL clones, but affected the lytic step of those clones. Our data indicate that LFA-1 is a major adhesion molecule in the CTL reaction, whereas the Tcr/CD3 complex is implicated in a phase after the initial formation of conjugates. CD8 is associated with both steps in the cytolytic reaction. In addition to its minor role in the adhesion phase, our data suggest strongly that CD-8 is involved in the triggering phase of the cytolytic reaction.
In vitro and in vivo activation of human mononuclear phagocytes by interferon-gamma. Studies with normal and AIDS monocytes.
Authors: Murray H W , Scavuzzo D , Jacobs J L , Kaplan M H , Libby D M , Schindler J , Roberts R B 
Published: December 2022

Abstract
To determine the potential immunotherapeutic role of interferon-gamma (IFN-gamma) as a mononuclear phagocyte-activating agent, we examined the effector cell function of peripheral blood monocytes from healthy donors and acquired immunodeficiency syndrome (AIDS) patients after either in vitro and/or in vivo treatment with recombinant (r) IFN-gamma. When assayed immediately after a 24-hr in vitro pulse with 300 U/ml, normal and AIDS monocytes behaved similarly with little augmentation of their intrinsically high levels of H2O2 release and activity against Toxoplasma gondii; in contrast, activity toward the more resistant intracellular pathogen, Leishmania donovani, was appreciably enhanced by rIFN-gamma. In addition, upon testing 4 to 6 days after in vitro pulsing, both normal and AIDS monocytes showed clear evidence of persistent activation in all three assays. The capacity of IFN-gamma to similarly activate monocytes in vivo was confirmed in all ten treated AIDS patients by examining cells before and after 24-hr infusions of 0.03 and 0.5 mg of rIFN-gamma/square meter (M2) of body surface area. For postinfusion monocytes tested after 1 day in culture, H2O2 release and antitoxoplasma activity were essentially unchanged, but antileishmanial effects were augmented. After 5 to 7 days in culture, monocytes from treated patients showed 3.2- to 5.9-fold increases in H2O2-releasing capacity and increases of 49 to 68% and 35 to 61% in intracellular activity against T. gondii and L. donovani, respectively. These results indicate that the human monocyte can be induced by rIFN-gamma to express signs of both immediate and persistent activation and suggest that, as a direct activator of mononuclear phagocytes, rIFN-gamma may also have potential as an immunotherapeutic agent for patients with intracellular infections.
Anti-T cell monoclonal antibodies in vivo. II. Modulation of acute and chronic experimental allergic encephalomyelitis (EAE) in guinea pigs.
Authors: Sobel R A , Blanchette B W , Russo M A , Williams A M , Colvin R B 
Published: December 2022

Abstract
To determine the effects of anti-T cell monoclonal antibody-induced systemic T cell depletion in neuro-autoimmune disease, we studied the in vivo effects of 8BE6, a mouse anti-guinea pig (GP) pan-T cell monoclonal antibody, on the course and immunopathology of the disease model experimental allergic encephalomyelitis (EAE) in adult Strain 13 GP. Central nervous system (CNS) tissues were studied by routine histology and by an immunoperoxidase staining technique using monoclonal antibodies to T cells, IgM, and macrophages. From 3 days before to 10 days after sensitization with GP spinal cord and complete Freund's adjuvant, the GP were given one or two i.p. doses of 3.4 mg 8BE6 or MOPC 21, the parent mouse myeloma ascites, or normal saline. Eighteen of 18 control-treated GP developed typical acute, paralytic EAE 11 to 21 days after sensitization, whereas acute EAE was prevented in 33 of 49 8BE6-treated GP (67%), and the onset was delayed and disease progression was slowed in the others. Five GP treated with 8BE6 from days 11 to 14 after sensitization, at the onset of neurologic signs, rapidly deteriorated within hours after treatment and had loss of T cell staining, and lymphocytolysis in the CNS. 8BE6-treated GP which did not develop acute EAE were observed daily for up to 700 days (mean = 213 days). Twenty-nine of 39 (74%) had from one to six relapses or fixed neurologic deficits. GP in relapse were additionally treated with 8BE6 (22), MOPC-21 (5), or saline (6) in a cross-over protocol. Clinical scores were improved from days 2 to 12 after treatment (p less than 0.05), and complete recovery within 30 days occurred more frequently (p = 0.046) and more rapidly (p less than 0.01), after 8BE6 as compared with control treatments. Recoveries occurred more often if 8BE6 was given early in the relapse. Multiple treatments led to dose-dependent levels of serum antibodies to mouse immunoglobulin detected by an ELISA. There were no differences between acute and chronic EAE in numbers of inflammatory foci or numbers of macrophages and T cells in CNS infiltrates, but GP with chronic EAE had more extensive demyelination and vascular fibrosis and more numerous IgM+ B cells in parenchymal and meningeal infiltrates than in acute EAE (p less than 0.001).(ABSTRACT TRUNCATED AT 400 WORDS)
Interleukin 1 modulates messenger RNA levels of lymphokines and of other molecules associated with T cell activation in the T cell lymphoma LBRM33-1A5.
Authors: Hagiwara H , Huang H J , Arai N , Herzenberg L A , Arai K , Zlotnik A 
Published: December 2022

Abstract
We have investigated the mechanism of action of IL 1 on T cell activation. For this purpose, we analyzed the content of specific messenger RNA for lymphokines and other genes that are associated with T cell activation in the murine IL 1-dependent T cell lymphoma LBRM33-1A5. Using cloned genes for IL 2, IL 3, TGF-beta, TY5, IL 2 receptor, Ly-1, c-myc, and p53 as probes in the S1 nuclease protection assay, we compared the amount of specific transcripts among total RNA prepared from unstimulated cells, IL 1 alpha or PHA-stimulated cells, and PHA plus IL 1 alpha-stimulated cells. IL 1 alpha augmented the PHA-induced accumulation of IL 2 mRNA with a magnitude comparable to the amount of IL 2 produced, suggesting that IL 1 alpha modulates IL 2 gene expression at the RNA level. Similar results were obtained with IL 3. We also observed that Ly-1 mRNA appears after PHA treatment and its accumulation was augmented by IL 1 alpha addition. On the basis of the effects of IL 1 alpha and/or PHA treatments on gene expression, we classified these genes into four groups. In all cases, IL 1 alpha seemed to affect mRNA levels quantitatively. These observations support previously described characteristics of this cytokine as a co-stimulator of T cell activation.
A B cell-specific differentiation antigen, CD23, is a receptor for IgE (Fc epsilon R) on lymphocytes.
Authors: Yukawa K , Kikutani H , Owaki H , Yamasaki K , Yokota A , Nakamura H , Barsumian E L , Hardy R R , Suemura M , Kishimoto T 
Published: December 2022

Abstract
Two independent L cell transformants expressing human lymphocyte Fc epsilon R were established by using cellular DNA from RPMI 8866 cells. The surface expression of the receptor was confirmed on the basis of the binding of a panel of anti-Fc epsilon R antibodies and its ability to bind IgE. Anti-CD23 antibodies strongly stained the transformants, indicating possible identity or antigenic relationship between Fc epsilon R and CD23. This interesting observation warrants additional clarification as to the role of CD23 and Fc epsilon R in B cell differentiation.