bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural and idiotypic characterization of the L chains of human IgM autoantibodies with different specificities.
Authors: Goñi F R , Chen P P , McGinnis D , Arjonilla M L , Fernandez J , Carson D , Solomon A , Mendez E , Frangione B 
Published: December 2022

Abstract
We have determined the V region amino acid sequence and/or serologic markers (kIIIb, PSL2, and PSL3) of 24 IgM monoclonal autoantibodies with specificities of anti-gamma-globulin (RF), anti-I (cold agglutinin), anti-low density lipoprotein and anti-intermediate filaments. The data emphasize the overwhelming selection of the HumKv325/VkIIIb L chain for this family of autoantibodies. The few amino acid substitutions found within the VL regions were mainly concentrated in the complementarity-determining region 1. JK and CK genes did not show the same pattern of restriction. There is a good correlation between the amino acid sequence and the presence of the kIIIb marker. The idiotypic marker PSL2 was present in 34 out of 35 kIIIb L chains analyzed (97%) and the PSL3 in 27 (80%). Moreover, the hydrophilicity and antigenic profiles of these L chains corroborate the presence of the epitopes detected by the anti-CRI. These results demonstrate a restricted selection of the Vk genes used by a family of self reacting proteins, and an unusual evolutionary conservation of the idiotypic structure that may be involved in the network regulation.
Fungicidal activity of IFN-gamma-activated macrophages. Extracellular killing of Cryptococcus neoformans.
Authors: Flesch I E , Schwamberger G , Kaufmann S H 
Published: December 2022

Abstract
Cryptococcus neoformans is an encapsulated yeast-form fungus which causes pulmonary and meningeal infections preferentially in the immunocompromised host. It is thought that cell-mediated immunity is important for acquired resistance against cryptococcosis with activated macrophages as the final effector cells. However, specific polysaccharides in the capsule of C. neoformans protect the fungus from adherence to phagocytes and from subsequent phagocytosis. We have studied extracellular killing of C. neoformans by IFN-gamma-activated macrophages and their products. Murine bone marrow-derived macrophages stimulated with rIFN-gamma for 24 h were able to effectively suppress the growth of C. neoformans and the effect of IFN-gamma was augmented by LPS. Killing of C. neoformans was also achieved by cell-free supernatants from bone marrow-derived macrophages stimulated with IFN-gamma plus LPS. Our results indicate that killing of C. neoformans by activated macrophages is independent from toxic oxygen radicals and mediated by secreted protein(s) of apparent molecular mass of 15 and 30 kDa. These findings indicate that activated macrophages play a major role in host defense, although the fungus resists phagocytosis and remains in the extracellular milieu.
A monoclonal antibody to the IL-1 beta peptide 163-171 blocks adjuvanticity but not pyrogenicity of IL-1 beta in vivo.
Authors: Boraschi D , Volpini G , Villa L , Nencioni L , Scapigliati G , Nucci D , Antoni G , Matteucci G , Cioli F , Tagliabue A 
Published: December 2022

Abstract
The synthetic fragment VQGEESNDK, corresponding to the amino acid sequence in position 163-171 of human IL-1 beta, possesses the immunostimulatory but not the pyrogenic activity of the mature IL-1 beta polypeptide in vivo. To assess the relevance of this domain of IL-1 beta for its biologic activities, a mAb was raised against the synthetic peptide 163-171. The mAb Vhp20 could effectively recognize human rIL-1 beta in RIA and immunoblotting. In vivo, the mAb Vhp20 was able to selectively inhibit the immunostimulatory activity of IL-1 beta, but it could not affect the fever-inducing capacity of IL-1 beta. It is proposed that functional domains could be identified in the human IL-1 beta protein and that the fragment in position 163-171 is of major importance for the adjuvant capacity of the entire molecule, but irrelevant to its pyrogenic activity.
Expression of I-A by macrophages from Bcgr and Bcgs mice. Transient expression of I-A is due to degradation of MHC class II glycoproteins.
Authors: Vespa L , Zwilling B S 
Published: December 2022

Abstract
Murine peritoneal macrophages from mice that are resistant to Mycobacterium bovis (strain BCG) can be induced to continuously express MHC class II (Ia) glycoproteins. In contrast, macrophages from BCG susceptible mice will only transiently express Ia. The purpose of this investigation was to determine the biochemical basis of continuous or transient Ia expression. We therefore compared Ia biosynthesis by macrophages from C.D2Bcgr mice to that by macrophages from congenic BALB/c.Bcgs mice. We show that macrophages from both strains of mice synthesize Ia initially and that very little synthesis occurs after 5 days of in vitro culture. No differences in the amount of Ia synthesized by the macrophages was apparent as determined by quantitative immunoprecipitation and by ELISA. Despite the lack of synthesis, macrophages from C.D2Bcgr mice continue to express Ia. The results of pulse-chase experiments indicate that macrophages from BALB/c.Bcgs mice degrade newly synthesized MHC class II glycoproteins whereas the majority of Ia remains associated with macrophages from the C.D2Bcgr mice. The addition of chloroquine to cultures of macrophages from BALB/c.Bcgs mice prevented the degradation and prolonged the expression of Ia. The results of this investigation show that there are no differences in the synthesis of Ia by macrophages from the two congenic strains of mice. The transient expression of Ia by macrophages from BALB/c.Bcgs mice is due to its degradation.
Depletion of guanine nucleotides with mycophenolic acid suppresses IgE receptor-mediated degranulation in rat basophilic leukemia cells.
Authors: Wilson B S , Deanin G G , Standefer J C , Vanderjagt D , Oliver J M 
Published: December 2022

Abstract
In RBL-2H3 rat basophilic leukemia cells, Ag that crosslink IgE-receptor complexes stimulate the turnover of inositol phospholipids, the mobilization of Ca2+ from intra- and extracellular sources, the release of serotonin and other substances from granules and the transformation of the cell surface from a microvillous to a lamellar architecture. This study explores the role of GTP-binding proteins (G proteins) in the control of these biochemical and functional responses. We report that incubating RBL-2H3 cells for 4 h with 10 microM mycophenolic acid (MPA), an inhibitor of de novo GTP synthesis, reduces GTP levels by over 60% and causes an average reduction of 50% in Ag-stimulated serotonin release. This inhibition of secretion is associated with a 50% decrease in the rate of 45Ca2+ influx in MPA-treated cells. In contrast, Ag-stimulated inositol trisphosphate production is only slightly reduced, indicating that the phosphatidylinositol-specific phospholipase C can be activated by Ag in GTP-depleted cells. The membrane responses to IgE receptor cross-linking are unaffected by incubating cells with MPA. Exogenous guanine or guanosine protects the GTP pools in MPA-treated cells and permits normal ion transport and secretory responses to Ag; adenine does not. These results implicate a guanine nucleotide-binding protein in the control of IgE receptor-dependent signal transduction in RBL-2H3 cells. This protein may particularly control the Ca2+ influx pathway that is essential for secretion.
Administration of monoclonal anti-IFN-gamma antibodies in vivo abrogates natural resistance of C3H/HeN mice to infection with Leishmania major.
Authors: Belosevic M , Finbloom D S , Van Der Meide P H , Slayter M V , Nacy C A 
Published: December 2022

Abstract
C3H/HeN mice that are naturally resistant to cutaneous disease and systemic infections with the protozoan parasite, Leishmania major, were treated at the time of infection, and weekly thereafter, with mouse anti-rat IFN-gamma mAb or an irrelevant antibody of similar isotype. Anti-IFN-gamma-treated mice developed cutaneous lesions; parasites spread to the regional lymph nodes and then metastasized to spleens and livers. The course of disease in these animals was similar to that of genetically susceptible BALB/c mice. Two exceptions in the pathology of L. major infections were noted between BALB/c and anti-IFN-gamma-treated C3H/HeN mice: 1) BALB/c mice died of systemic complications, whereas C3H/HeN mice did not, and 2) multinucleated giant cells were observed in lymph nodes and spleens of infected BALB/c mice, whereas these cells were not observed in infected C3H/HeN mice. Control mice, those treated with either saline or irrelevant antibody of the same isotype as the anti-IFN-gamma monoclonal, showed no evidence of cutaneous disease (development of footpad lesions) or systemic infection (by histopathology). Total abrogation of the natural resistance of C3H/HeN mice could be achieved by treatment with as little as 0.5 mg/mouse/wk of anti-IFN-gamma antibody, or by a single dose of 1 mg/mouse anti-IFN-gamma antibody administered at the time of parasite inoculation. If antibody treatment was delayed for as little as 1 wk after parasite inoculation, the infections in treated animals resembled that of untreated or control antibody-treated mice: no cutaneous lesions (by footpad swelling or viable counts of leishmania in footpad tissue) or systemic disease (by microscopic analysis of touch preparations of internal organs, and histopathology of same). The production of IFN-gamma during the initial interaction of the parasite and host cells appears to be a major component of genetic control of natural resistance to infection with L. major in C3H/HeN mice.
Clonal characterization of the human IgG antibody repertoire to Haemophilus influenzae type b polysaccharide. II. IgG antibodies contain VH genes from a single VH family and VL genes from at least four VL families.
Authors: Scott M G , Tarrand J J , Crimmins D L , McCourt D W , Siegel N R , Smith C E , Nahm M H 
Published: December 2022

Abstract
To define the V gene family repertoire of human IgG anti-Haemophilus influenzae type b polysaccharide antibodies, we purified six IgG1 and nine IgG2 anti-Hib-PS antibodies to monoclonality from immune serum of six individuals and performed N-terminal amino acid sequence analysis. Of the 15 clonal antibodies we examined, all H chain V regions were of the VHIII family. In contrast, the L chains of these antibodies were clearly from at least four different VL families; VKI, VKII, VKIII, and V lambda. Interestingly. VL family expression correlated with the cross-reactivity of these antibodies to the capsular carbohydrate of Escherichia coli K100. VKII antibodies did not cross-react, whereas antibodies expressing V lambda, VKI, or VKIII generally cross-reacted. We conclude that L chain V regions are very important contributors to the limited heterogeneity in this antibody repertoire.
Macrophages and T cells do not express Mlsa determinants.
Authors: Molina I J , Cannon N A , Hyman R , Huber B T 
Published: December 2022

Abstract
In order to test the tissue distribution of Mlsa determinants, we have generated highly purified stimulator cell populations. First, Mlsa expression in bone marrow derived macrophages (M phi) of Mlsa genotype was tested in primary MLR and on Mlsa-specific T cell hybridomas (THy). Second, a similar experimental approach was used to analyze thioglycolate, peptone or Con A elicited peritoneal M phi. In all cases, these M phi cell populations were able to generate an excellent alloresponse, whereas no functional Mlsa determinants could be detected. Third, to further investigate whether the expression of Mlsa is lymphocyte specific, but dependent on expression of class II molecules, we have transfected I-Ek alpha and beta cDNA into a panel of thymomas of Mlsa genotype. Although we achieved a high level of surface I-Ek expression in all of these T cell tumors, none of them was able to trigger the Mlsa-specific THy. These results strongly suggest that Mlsa expression is limited to B cells. It is likely that Mlsa is a tissue-specific self-peptide that associates with class II molecules.
Immunodeficiency in graft-versus-host disease (GVHD). II. Effects of GVHD-induced suppressor cells on CD4+ T cell clones.
Authors: Wall D A , Hamberg S , Ferrara J L , Abbas A K 
Published: December 2022

Abstract
Lethally irradiated mice transplanted with H-2-matched, minor histocompatibility-disparate bone marrow develop graft-vs-host disease (GVHD) that is associated with severe immunodeficiency. Splenocytes from such mice contain radioresistant cells that profoundly suppress normal lymphocyte function. We now show that GVHD-induced suppressor cells also inhibit the proliferation of CD4+ T cell clones specific for different Ag and class II MHC determinants. These suppressors have a dominant anti-proliferative effect, because they inhibit DNA synthesis in response to receptor-mediated stimulation and growth-promoting lymphokines, without abolishing lymphokine secretion or lymphokine receptor expression by the cloned T cells. The implications of these findings, and the usefulness of T cell clones for studying immune suppression, are discussed.
T cell tolerance to self antigens in New Zealand hybrid mice with lupus-like disease.
Authors: Kotzin B L , Kappler J W , Marrack P C , Herron L R 
Published: December 2022

Abstract
We determined if self-reactive T cells are able to escape thymic tolerance in autoimmune New Zealand mice. T cells utilizing V beta 17a and V beta 11 encoded receptors have been shown to be clonally eliminated in nonautoimmune mice expressing I-E because of their potential self-reactivity. Similarly, V beta 8.1+ and V beta 6+ T cells are tolerized in the thymus of nonautoimmune mice that express Mls-1a. These T cell subsets were quantitated in the lymph nodes and spleens of (NZB x NZW)F1 and (NZB x SWR)F1 mice. In young mice from both autoimmune strains, deletion was similar to that observed in control animals matched for I-Ed and Mls-1a expression. Furthermore, older female autoimmune mice with elevated levels of IgG antinuclear antibodies and severe lupus-like renal disease did not demonstrate evidence of a global tolerance defect. We also found that the levels of residual V beta 17a+ cells in MHC-matched control F1 strains were further reduced by up to 80% in autoimmune (NZB x SWR)F1 mice. The greater in vivo elimination corresponded to an enhanced ability of NZB spleen cells, compared with other H-2d spleen cells, to stimulate V beta 17a+ hybridomas in vitro. The increased stimulation in culture could not be attributed to quantitative differences in I-E Ag expression. The results suggest that autoreactive T cells have been eliminated in these autoimmune mice by normal mechanisms of self-tolerance. Furthermore, the data demonstrate the existence of an NZB minor locus not present in other H-2d strains that influences T cell repertoire and enhances stimulation of T cells potentially reactive to self class II MHC Ag.
Heterogeneous distribution and transmembrane signaling properties of lymphocyte function-associated antigen (LFA-1) in human lymphocyte subsets.
Authors: Pardi R , Bender J R , Dettori C , Giannazza E , Engleman E G 
Published: December 2022

Abstract
The role of LFA-1, a member of the integrin supergene family, in intercellular adhesion, including lymphocyte-endothelial cell (EC) binding, has been established. We now demonstrate that differences in LFA-1 cell surface density are responsible for the variable adhesion efficiency of lymphocyte subsets to EC. Electrophoretic analysis revealed multiple glycosylated isoforms of both alpha and beta subunits, largely as a result of different degrees of sialylation, with variable expression among different lymphocyte subsets. Neuraminidase digestion before EC adhesion increased the binding efficiency of all lymphocyte subsets, although the relative increase in each subset was proportional to the initial LFA-1 sialic acid content. LFA-1 cross-linking resulted in phosphoinositide hydrolysis and a rise in [Ca2+]i when using anti-alpha but not anti-beta subunit antibodies. These findings indicate that the density of LFA-1 on lymphocyte subsets controls their adhesive properties, and that the LFA-1 alpha subunit has transmembrane signaling properties that may result in activation events after interaction with its natural ligands.
Activation of murine T cells by toxic shock syndrome toxin-1. The toxin-binding structures expressed on murine accessory cells are MHC class II molecules.
Authors: Uchiyama T , Tadakuma T , Imanishi K , Araake M , Saito S , Yan X J , Fujikawa H , Igarashi H , Yamaura N 
Published: December 2022

Abstract
Toxic shock syndrome toxin-1 (TSST-1)-binding structures present on murine lymphoid tissues were investigated by using 125I-TSST-1. T-depleted C57BL/6 spleen cells incubated with TSST-1 for 3 h at 0 degree C were mitogenic to splenic T cells, indicating that the former cells bind and present TSST-1 to T cells. TSST-1-binding activity was observed in C57BL/6 splenic B cells and L cells transfected with I-Ab genes, but not in splenic T cells and control L cells. Scatchard plot analysis showed that these B cells and transfectants bound TSST-1 with similar binding affinity. SDS-PAGE analysis showed that lysates of C57BL/6 spleen cells and the I-Ab-positive transfectants contain a single band which bound TSST-1 and comigrated with I-Ab heterodimers. TSST-1-binding activity observed clearly in C57BL/6. BALB/c, and C3H/HeN spleen cells and L cells transfected with I-Ab or I-Ak genes was not reduced by paraformaldehyde fixation. Binding of 125I-TSST-1 to the three spleen cells was markedly reduced by anti-I-A antibodies, but not by anti-I-E antibodies. C57BL/6, C3H/HeN, and (C3H/HeN x C57BL/6) F1 T cells were activated by TSST-1 to proliferate and produce IL-2 in the presence of FT6.2 cells, LT1-30-3 cells and either of them, respectively, but not in the presence of control L cells. These results indicate that I-A molecules function as the structures via that accessory cells directly bind TSST-1 on the cell surface and present a triggering signal of TSST-1 to T cells.
The antiinflammatory effects of essential fatty acid deficiency in experimental glomerulonephritis. The modulation of macrophage migration and eicosanoid metabolism.
Authors: Schreiner G F , Rovin B , Lefkowith J B 
Published: December 2022

Abstract
Dietary polyunsaturated fatty acid modulation exerts a beneficial effect in immune-mediated glomerulonephritis. To elucidate the mechanisms underlying this phenomenon, the effects of essential fatty acid (EFA) deficiency on the heterologous phase of nephrotoxic nephritis in rats (induced by the injection of a rabbit antiglomerular basement membrane antibody) were studied. The heterologous phase of nephrotoxic nephritis was characterized by an invasion of leukocytes into the glomerulus. Polymorphonuclear neutrophils predominated early on (3 h), whereas macrophages predominated at 24 and 72 h. EFA deficiency selectively prevented the influx of macrophages into the glomerulus. The invasion of polymorphonuclear neutrophils, in contrast, was unaffected. The influx of leukocytes into the glomerulus during nephritis was accompanied by a marked enhancement (10- to 40-fold) in glomerular thromboxane and leukotriene B4 production. EFA deficiency largely attenuated this change. Renal dysfunction during the heterologous phase of nephritis was manifested as azotemia, polyuria, sodium retention, and proteinuria. With EFA deficiency, polyuria, azotemia, and sodium retention were not seen. Proteinuria was reduced by approximately 85%. To address whether the lack of macrophage migration into the glomerulus in the context of nephritis with EFA deficiency might be due to a functional defect in macrophage migration, the chemotactic responsiveness of EFA-deficient macrophages was examined. EFA-deficient macrophages displayed normal chemotactic migration toward activated C. In sum, EFA deficiency prevents the invasion of macrophages into the glomerulus in nephrotoxic nephritis and attenuates the accompanying metabolic and functional alterations, but does not affect macrophage chemotactic responsiveness. Alterations in macrophage elicitation and lipid mediator generation by inflamed glomeruli thus appear to be central to the salutary effect of dietary polyunsaturated fatty acid modification on glomerulonephritis.
Transforming growth factor-beta inhibits the generation of cytotoxic T cells in virus-infected mice.
Authors: Fontana A , Frei K , Bodmer S , Hofer E , Schreier M H , Palladino M A , Zinkernagel R M 
Published: December 2022

Abstract
The immunoregulatory effects of human recombinant transforming growth factor (rTGF) beta 1 and human recombinant glioblastoma-derived T cell suppressor factor (rG-TsF)/TGF beta 2 was investigated in mice infected with lymphocytic choriomeningitis virus (LCMV) or vaccinia virus. Starting on the day of infection, i.p. injections of 1 microgram/day or rTGF-beta 1 or rG-TsF/TGF-beta 2 suppressed the generation of virus specific CTL. The effect of TGF-beta on CTL (day 8) was less pronounced when TGF-beta treatment was delayed for 3 days after LCMV infection. rG-TsF/TGF-beta 2 also has an inhibiting effect on CTL-mediated disease in LCMV-infected mice: it prolonged the survival time of mice infected with LCMV and reduced the local swelling reaction after infection into the footpad. These results indicate that rTGF-beta 1 and rG-TsF/TGF-beta 2 influence T cell immune reactivity in vivo.
1F7, a novel cell surface molecule, involved in helper function of CD4 cells.
Authors: Morimoto C , Torimoto Y , Levinson G , Rudd C E , Schrieber M , Dang N H , Letvin N L , Schlossman S F 
Published: December 2022

Abstract
We have developed a monoclonal antibody, anti-1F7, that inhibits soluble Ag-driven T cell proliferation as well as PWM-driven IgG synthesis. Anti-1F7 antibody reacts with approximately 57% of unfractionated T cells, 62% of CD4+ cells, and 54% of CD8+ cells. Although the 1F7 Ag is widely distributed among lymphoid cells, this Ag on CD4+ cells is preferentially expressed on the CDw29(4B4+) helper population. Moreover, anti-1F7 antibody further subdivides the CD4+CDw29+ cell subset into CDw29+1F7+ and CDw29+1F7- populations. The CD4+CDw29+1F7+ population of cells maximally proliferates to recall Ag such as tetanus toxoid, whereas helper function for PWM-driven IgG synthesis by B cells belongs to both the CD4+CDw29+1F7+ and CD4+CDw29+1F7- population of cells. The most prominent structure defined by this antibody is a 110-kDa molecule that is different from the 135-kDa, 160-kDa, and 185-kDa glycoproteins identified by anti-CDw29 antibody and the 180-kDa glycoprotein identified by UCHL-1 antibody. It is, however, related to the molecule recognized by anti-Ta1, an activation Ag on T cells. Furthermore, although the Ta1 molecule is recognized by anti-1F7 mAb, the 1F7 family of structures also includes molecules distinct from Ta1.