bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased superoxide anion release from human endothelial cells in response to cytokines.
Authors: Matsubara T , Ziff M 
Published: December 2022

Abstract
To study the effects of macrophage and lymphocyte-derived factors on superoxide anion (O2-) generation and release from human umbilical vein endothelial cells (EC), cultured EC were stimulated by ultrapure interleukin 1 (IL 1) and recombinant interferon-gamma (IFN-gamma), and the O2- released into the supernatant was measured. Both of these cytokines enhanced O2- release in a dose and time-dependent manner. Addition of a combination of IL 1 and IFN-gamma, each in submaximal concentration, produced an additive effect on O2- release. It would appear from these findings that cytokines released by macrophages and lymphocytes during inflammatory reactions can promote O2- generation and release from human EC. O2- released from EC may alter the basement membrane of blood vessels and the surrounding connective tissue, and in this way promote the vascular injury and angiogenesis associated with local inflammation.
Alterations in the amino-terminal third of mouse interleukin 2: effects on biological activity and immunoreactivity.
Authors: Zurawski S M , Mosmann T R , Benedik M , Zurawski G 
Published: December 2022

Abstract
In this report, we describe plasmids that direct the expression of active mouse interleukin 2 (mIL 2) in Escherichia coli, and the use of this expression system to perform a mutational analysis of the N-terminal region of the mIL 2 protein. We found that the N-terminus was tolerant to the addition of a few amino acids, and even the addition of 20 amino acids resulted in only a modest decrease in activity of the protein. The bioactivity of mIL 2 as defined by its ability to sustain the proliferation of cloned T cells was also only minimally affected by deletion of up to 13 N-terminal amino acids, or of the entire poly-GLN stretch (amino acids 15-26). Deletion of the 30 N-terminal amino acids drastically reduced but did not abolish activity. Deletion of the 41 N-terminal amino acids completely abolished activity, whereas certain changes in the initial 37 amino acids drastically reduced the biological activity of the protein. We also analyzed the immunoreactivity of the mutant proteins with the anti-IL 2 monoclonal antibodies S4B6 and DMS-1. This analysis showed that the determinant recognized by S4B6 required that the N-terminal mIL 2 amino acids 26-45 be intact, whereas the DMS-1 determinant was located to the C-terminal side of amino acid 46.
Cell-sized, supported artificial membranes (pseudocytes): response of precursor cytotoxic T lymphocytes to class I MHC proteins.
Authors: Goldstein S A , Mescher M F 
Published: December 2022

Abstract
Novel cell-sized, supported artificial membranes bearing class I antigens have been prepared by a simple dialysis procedure and then used to study the requirements for antigen recognition by precursor cytotoxic T lymphocytes (CTL). The membranes were made by mixing lipid, H-2 antigen, and C18 alkylated 5 microns silica beads in deoxycholate, and dialyzing to remove the detergent. The H-2 antigen-bearing, cell-sized beads, termed pseudocytes (artificial cells), were able to simulate generation of secondary CTL responses with the same specificity as alloantigen-bearing spleen cells. Comparative analyses demonstrated that the size of an antigen-bearing structure, and thus its potential for multivalent interaction, was a critical determinant of effectiveness of antigen recognition, and showed that H-2 antigen was recognized as effectively on cell-sized beads as on allogeneic spleen cells. Generation of a response to antigen on the cell-sized beads was completely dependent on addition of lymphokines to the cultures. Thus, unlike liposomes, H-2 antigen on beads was not available to accessory cells for stimulation of Ia-dependent production of lymphokines by T helper cells. These results, as well as direct observations by microscopy, strongly indicate that antigen is recognized on the surface of the beads. Despite effective stimulation of secondary CTL responses, antigen on beads was completely inactive in stimulating a primary CTL response by naive spleen cells. The results of mixing experiments by using beads and alloantigen-bearing cells or plasma membrane vesicles indicate that the lack of a primary response may result from a requirement for a soluble factor(s) that is not needed for generation of secondary responses. The unique advantages of cell-size supported membranes for studying antigen recognition by T cells are discussed. The beads can be handled and used like antigen-bearing cells in functional assays, while possessing well-defined, readily varied, and easily quantitated composition.
Lymphoid bone marrow cultures can reconstitute heterogeneous B and T cell-dependent responses in severe combined immunodeficient mice.
Authors: Dorshkind K , Denis K A , Witte O N 
Published: December 2022

Abstract
Long-term lymphoid bone marrow cultures (LBMC) produce B lymphocytes and their precursors for several months in vitro. To assess their differentiative potential and determine their capacity to function as immune effectors, cells from the cultures were transplanted into mice with severe combined immune deficiency disease (SCID). SCID mice are deficient in T and B lymphocytes and are serum immunoglobulin (Ig) negative, but grafts of normal lymphoid precursors can expand and differentiate in them, thereby restoring immunocompetence. The results of these studies indicate that cells from LBMC are able to reconstitute splenic B lymphocytes in the SCID mice. Upon in vivo transfer, LBMC cells secreted Ig that displayed isotype distribution and a pattern of heterogeneity comparable with normal BALB/c mice, as determined by two-dimensional gel electrophoresis. The transplanted LBMC cells were functional, because reconstituted mice could respond to immunization with the T-independent antigen TNP-Ficoll. The results also indicate that cultured cells could reconstitute T cell activity in SCID mice. Splenocytes from approximately one-third of the recipients could generate a cytotoxic response to alloantigens after 5 days of sensitization in a mixed lymphocyte culture, and all reconstituted SCID mice could respond to immunization with the T cell-dependent antigen TNP-BSA. These results demonstrate that B cells, as well as T cell activity, are present in LBMC-reconstituted SCID mice, and show that LBMC cells have the capacity to mediate an immune response.
Localization of biologic functions of toxic shock syndrome toxin-1 by use of monoclonal antibodies and cyanogen bromide-generated toxin fragments.
Authors: Blomster-Hautamaa D A , Novick R P , Schlievert P M 
Published: December 2022

Abstract
Monoclonal antibodies (mAb) against toxic shock syndrome toxin-1 (TSST-1) were generated that block two of the most important biologic activities of TSST-1, nonspecific T lymphocyte mitogenicity and the suppression of immunoglobulin synthesis. Fourteen hybridomas producing antibody against TSST-1 were isolated independently. The culture supernatant and ascitic fluids from each were analyzed to determine the mAb isotypes. Seven of the mAb were IgG1, and the remaining seven were IgM; all the mAb had kappa light chains. Immunoglobulin was partially purified from hybridoma-generated ascitic fluid by ammonium sulfate precipitation and tested for the ability to block TSST-1-induced mitogenicity and immunosuppression. Three mAb (all IgG1) were shown to block both the toxin-induced mitogenicity and the suppression. None of the mAb tested inhibited just one of the two toxin activities. The neutralizing mAb were then used in Western analysis with previously mapped cyanogen bromide (CNBr)-generated toxin fragments to localize the aforementioned biologic functions. The Western blot analysis showed that the mitogenic and the suppressive functions of TSST-1 were located on a 14,000 dalton internal CNBr fragment.
Induction of c-fos and c-myc expression in T lymphocytes after treatment with recombinant interleukin 1-alpha.
Authors: Kovacs E J , Oppenheim J J , Young H A 
Published: December 2022

Abstract
Our data demonstrate that an early-acting differentiation/growth factor, such as IL 1, can induce the sequential expression of c-fos and c-myc in lymphocytes. Because such a wide variety of agents induces c-onc expression in lymphocytes, we conclude that the expression of these cellular proto-oncogenes represents a common pathway of response of lymphocytes to an exogenous stimulatory signal regardless of the nature of the factor and its receptor.
Distinct signals are required for proliferation and lymphokine gene expression in murine T cell clones.
Authors: Heckford S E , Gelmann E P , Agnor C L , Jacobson S , Zinn S , Matis L A 
Published: December 2022

Abstract
Experiments were performed to assess the capacity of lectin (Con A), ionomycin, phorbol ester (PMA), and recombinant IL 2 to mediate proliferation as well as the expression of cell surface IL 2 receptors, two lymphokine genes, IL 2 and IFN-gamma, and the c-myc proto-oncogene in cloned T cell populations. Stimulation of T cell clones with recombinant IL 2 resulted in proliferation and sustained expression of the c-myc cellular proto-oncogene, but did not induce the expression of mRNA for the lymphokines IFN-gamma and IL 2. In contrast, stimulation of cloned T cells with lectin alone induced significant IFN-gamma and IL 2 mRNA expression, up-regulation of the number of cell surface IL 2 receptors, and transient c-myc expression. Ionomycin alone was not a sufficient signal for lymphokine mRNA induction. The phorbol ester PMA alone induced neither proliferation nor lymphokine gene expression but potentiated lectin and ionomycin-mediated signals. We also performed experiments to examine whether the T cell response to extracellular stimuli was a function of the activation state of the cell. Reexposure of 48-hr antigen-activated cloned cells to identical stimuli revealed several differences. Low but significant levels of IFN-gamma mRNA were now also reinduced in activated clones cells in response to IL 2 or PMA alone. Activated cells were refractory to reinduction of IL 2 mRNA by any stimulus, which may reflect a physiologic mechanism to limit clonal expansion after antigenic stimulation. This could be partially reversed by restimulation with lectin in the presence of cycloheximide, suggesting a role for a labile protein repressor in the down-regulation of IL 2 mRNA expression. PMA alone induced an IL 2-independent proliferative response. We demonstrate that distinct signals are required for lymphokine gene expression vs cellular proliferation in cloned T lymphocyte populations, and that the capacity of extracellular stimuli to reinduce expression of lymphokine genes or to mediate cell proliferation is altered by prior activation.
Eradication of disseminated murine leukemia by treatment with high-dose interleukin 2.
Authors: Thompson J A , Peace D J , Klarnet J P , Kern D E , Greenberg P D , Cheever M A 
Published: December 2022

Abstract
Interleukin 2 (IL 2) in high concentration induces lymphocytes to become nonspecifically cytolytic to a wide variety of tumor targets. We evaluated the therapeutic potential of such lymphokine-activated killer (LAK) cells in vivo and high-dose II 2 in vivo against disseminated murine leukemia. To quantitate the potential anti-leukemia effect of LAK cells in vivo, B6 mice were injected i.p. with graded doses of FBL-3 leukemia cells followed by LAK cells. In this Winn-type assay, 1 X 10(7) LAK cells were able to prevent the outgrowth of 1 X 10(2) FBL-3 cells in only 50% of mice and did not prevent the outgrowth of 1 X 10(6) tumor cells. Thus LAK cells, highly cytolytic to FBL-3 in vitro, mediated only a limited anti-tumor effect when applied directly to leukemia cells in vivo. LAK cells used as an adjunct to chemotherapy induced a small but non-curative effect against FBL-3, however. In this circumstance, LAK cells were markedly less effective than were immune spleen cells from mice previously sensitized to FBL-3. To test the anti-leukemia effect of high-dose IL 2 in vivo, B6 mice were inoculated with 5 X 10(6) FBL-3 cells followed by repeated doses of IL 2 at dose levels shown to induce LAK in vivo. "LAK-inducing" IL 2 doses on days 5 to 9 after FBL-3 inoculation, when tumor was disseminated, cured 50% of the mice. Treatment on days 5 to 9 was far more effective than on days 0 to 4, implying that the evolution of a host-tumor interaction was essential for the therapeutic effect of IL 2. Mice cured of FBL-3 by high-dose IL 2 were found to be immune to FBL-3, suggesting that tumor eradication resulted from a collaboration between LAK activity and tumor-specific immunity.
The NK-1.1(-) mouse: a model to study differentiation of murine NK cells.
Authors: Koo G C , Dumont F J , Tutt M , Hackett J , Kumar V 
Published: December 2022

Abstract
The NK-1.1(-) mouse was constructed by weekly injections of monoclonal anti-NK-1.1 antibody from birth through adulthood. Spleen cells from these mice have decreased NK-1.1+ cells and null (Thy-1- and B220-) cells. Their splenic NK activity to YAC targets was low and was not enhanced by IFN-alpha or IFN-beta. Bone marrow (BM) of these NK-1.1(-) mice have normal precursors to NK cells: 1) NK activity could be generated from NK-1.1(-) BM cells cultured in rIL 2 for 5 to 6 days. These cultured BM cells expressed Qa-5, Thy-1, AsGm-1, and NK-1.1 antigens. The precursor cells of these BM cytotoxic cells are NK-1.1-; 2) transfer of BM cells from the NK-1.1(-) mice reconstituted the NK activity of irradiated, NK-depleted recipients. Lymphokine-activated killer cells could also be generated from spleens of these NK-1.1(-) mice. Therefore, the NK-1.1(-) mice were specifically depleted of mature cytotoxic NK cells, but not the NK-1.1- precursors of NK cells. This mouse model is valuable to study ontogeny and physiologic relevance of NK cells.
A human autoreactive T cell line specific for minor histocompatibility antigen(s) isolated from a bone marrow-grafted patient.
Authors: Tilkin A F , Bagot M , Kayibanda M , Vernant J P , Levy J P 
Published: December 2022

Abstract
A human autoreactive T cell line named Bur-1 has been obtained from a woman 4 mo after an allogeneic bone marrow transplantation (BMT) from one of her HLA-identical brothers. The phenotype of the cell line is 100% T11+ and over 90% T4+, and the karyotype confirms its donor (male) origin. These donor T cells proliferate specifically in the presence of donor's peripheral blood monocytes (PBM) but not recipient's cells, and they kill specifically donor's but not recipient's Epstein-Barr virus (EBV)-induced lymphoblastoid cell lines (LCL). PBM from another HLA-identical brother and from several unrelated donors also stimulate Bur-1 cells, and EBV-induced LCL from the same donors are killed in cytotoxicity assays. All of these donors share HLA-DR5 or HLA-DRw11 (the major split of HLA-DR5) with Bur-1 cells. However, some but not all of the PBM sharing HLA-DR5 with Bur-1 cells are recognized. Therefore, in contrast with the previously described autoreactive T cells, Bur-1 cells are not directed against self-MHC antigens but rather recognize autologous minor histocompatibility (mH) antigens in the context of autologous HLA class II molecules. Because both male and female cells can be recognized, the reacting minor antigen could not be the male-specific HY antigen. It is suggested that autoreactivity against mH antigens can be observed in bone marrow-grafted patients due to the education of bone marrow donor precursors in the recipient thymus not allowing tolerance to autologous (donor) mH antigens not shared by the recipient.
Anti-thyroglobulin anti-idiotypic antibodies in sera of patients with Hashimoto's thyroiditis and Graves' disease.
Authors: Sikorska H M 
Published: December 2022

Abstract
The objective of this study was to find naturally occurring anti-idiotypic (anti-Id) antibodies to anti-human thyroglobulin (anti-hTg) idiotype in sera of patients with autoimmune thyroid disease. Sera from patients with Hashimoto's thyroiditis (HT), Graves' disease (GD), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) and sera from normal subjects were tested for the presence of anti-Id antibodies against mouse anti-hTg monoclonal antibodies (McAb) in indirect ELISA and in indirect solid-phase RIA. Microtitration plates were coated with six McAb, five of them directed against different epitopes on hTg molecule, and then incubated with patients' sera. The bound antibody was detected with either peroxidase or 125I-labeled anti-human IgG. The specific positive reaction was observed in four of 40 patients with HT, in two of 26 patients with GD, in seven of 58 patients with RA, and in none of 20 normal subjects. The detected binding was due to the presence of anti-hTg anti-Id antibodies and not to Tg-anti-Tg circulating immune complexes, as the positive sera did not contain hTg when resolved on SDS-PAGE, nor did they bind to all anti-hTg McAb tested. The binding was dose dependent, and titers of anti-Id antibodies varied from 1:243 to 1:2187. The binding could be inhibited up to 50% by hTg, but not by the thyroid microsomal antigen, indicating that some of those anti-Id might represent the internal image of the antigen. Serum from the patient 3403, showing the strongest reactivity against McAb A-3, was chosen for IgG purification and F(ab')2 fragment isolation. The 3403 F(ab')2 fragment, but not the Fc fragment, was found to react specifically with four mouse anti-hTg McAb but not with the control mouse IgG. Thus, the obtained results permit the conclusion that anti-hTg anti-Id antibodies could occur naturally during the course of thyroid autoimmune disorders.
DM-20, a proteolipid apoprotein, is an encephalitogen of acute and relapsing autoimmune encephalomyelitis in mice.
Authors: Endoh M , Tabira T , Kunishita T , Sakai K , Yamamura T , Taketomi T 
Published: December 2022

Abstract
Experimental allergic encephalomyelitis (EAE) was successfully induced in BALB/c mice with DM-20, a protein component of proteolipid apoprotein. DM-20 was separated by ion exchange column chromatography with CM-Trisacryl from proteolipid apoprotein obtained from bovine spinal cords. Its purity was ascertained by SDS-polyacrylamide gel electrophoresis, a dot immunobinding procedure, and amino acid analysis. Nine of 15 animals with a single injection of 100 micrograms of DM-20 and five of seven animals with a booster injection developed hind leg paralysis or axial rotatory movement 16 to 27 days after sensitization (mean 21.3 days). Five of the 14 animals relapsed 2 to 6 wk after the first attack. Histological examination revealed inflammatory lesion, with significant demyelination in the central nervous system. Antibody levels to DM-20 were not related to the clinical signs. Five of 11 BALB/c nude mice reconstituted with T cells developed similar clinical and pathologic signs. This DM-20-induced EAE in mice may provide a valuable model because it is similar to multiple sclerosis and because it can be induced in inbred mice in which immune mechanisms can be easily studied.
Interleukin 2 induction of interferon-gamma mRNA synthesis.
Authors: Farrar W L , Birchenall-Sparks M C , Young H B 
Published: December 2022

Abstract
Interleukin 2 (IL 2) induces specific mRNA synthesis and secretion of an important immunoregulatory molecule, interferon-gamma (IFN-gamma). We have observed that treatment of an IL 2 independent murine T cell line, BUD-27, with IL 2, calcium ionophore A23187, or agents that activate phospholipid/Ca2+-dependent protein kinase C results in increased IFN-gamma mRNA transcription and release of anti-viral activity. These same agents each induced the subcellular redistribution of protein kinase C from cytosol to plasma membrane in both the BUD-27 cell line and its IL 2-dependent parent, CT6. Ionophore concentrations greater than 1 micron exhibited the most significant induction of IFN-gamma mRNA, which also correlated with the dose of ionophore, inducing translocation of protein kinase C. This correlation between increased mRNA levels and protein kinase C translocation suggests that a calcium-dependent event is involved in induction of IFN-gamma mRNA synthesis. Furthermore, the magnitude of the translocation of protein kinase C from cytosol to plasma membrane corresponded to the physiologic IL 2 dose-response for IFN-gamma secretion. The data suggest that the activation of protein kinase C and/or coordinate elevation of intracellular calcium may provide at least one mechanism of signal transduction for the regulation of IFN-gamma gene transcription.
Human interferon-gamma acts as a B cell growth factor in the anti-IgM antibody co-stimulatory assay but has no direct B cell differentiation activity.
Authors: Defrance T , Aubry J P , Vanbervliet B , Banchereau J 
Published: December 2022

Abstract
In this study it is illustrated that recombinant human interferon-gamma (IFN-gamma) acts as a B cell growth factor (BCGF) in the anti-IgM antibody co-stimulatory assay. A monoclonal antibody that specifically inhibits the biological activities of IFN-gamma blocks its BCGF activity supporting the specificity of the IFN-gamma effect. Various IFN-gamma obtained from different sources displayed the same BCGF activity. Nonactivated B lymphocytes do not proliferate in response to IFN-gamma. IFN-gamma acts directly on B cells because highly purified B cells obtained after standard purification procedures coupled to cell sorting could still proliferate in response to IFN-gamma. Blood B lymphocytes were found to be more sensitive to the BCGF activity of IFN-gamma than B cells obtained from spleens or tonsils. The IFN-gamma-induced proliferation of B cells was short lasting when compared with that of recombinant IL 2 or BCGF containing T cell clone supernatants. B cells preactivated with either Staphylococcus aureus strain Cowan I (SAC) or optimal concentrations of anti-IgM antibodies coupled to beads did not proliferate in response to IFN-gamma, whereas they proliferated in response to IL 2 or T cell clone supernatants. IFN-gamma did not stimulate nor inhibit the proliferative response of human B lymphocytes stimulated with optimal concentrations of anti-IgM antibodies or SAC. Additionally none of the different IFN-gamma tested had B cell differentiation factor activity in the standard SAC assay. These results indicate that IFN-gamma sensitizes B cells to suboptimal mitogenic concentrations of anti-IgM antibody.