bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defective isotype-specific regulation of IgA anti-erythrocyte autoantibody-forming cells in NZB mice.
Authors: Moore J S , Hoover R G 
Published: December 2022

Abstract
B cell hyperactivity characterizes many autoimmune diseases. In NZB mice this is manifested by a variety of immunologic aberrations, including increased B cell proliferation and hyper IgM and IgA secretion in vitro. Recent studies have shown that IgA secretion can be suppressed or enhanced in an isotype-specific manner by a soluble factor(s), called IgA-binding factor (IgABF), produced by IgA FcR-bearing T cells. We now show that T cells from young NZB mice, cultured with high concentrations of IgA, produce an IgABF that has aberrant biologic activity when compared to IgABF produced from IgA FcR+ T cells of BALB/c mice. Although BALB/c IgABF normally suppresses proliferation and secretion by IgA-producing B cells, neither proliferation nor IgA secretion from normal murine IgA-B cells is suppressed by NZB IgABF. In fact, IgA secretion is significantly enhanced by NZB IgABF. We also present the first evidence of IgA anti-mouse erythrocyte (anti-MRBC) autoantibody-forming cells present in the spleens of NZB mice. Whereas BALB/c IgABF suppresses the in vitro generation of IgA anti-MRBC autoantibody-forming cells by NZB spleen cells, NZB IgABF enhances this response. Of particular interest is the development of IgA anti-MRBC autoantibody-forming cells in cultures of spleen cells from nonautoimmune BALB/c mice in the presence of NZB IgABF. These studies suggest that isotype-specific T cells factors might play an important role in the development of autoantibody-forming cells.
Aberrant expression of class II MHC antigens by skeletal muscle endothelial cells in experimental autoimmune myositis.
Authors: Rosenberg N L , Kotzin B L 
Published: December 2022

Abstract
We recently described the induction of an inflammatory myopathy in SJL/J mice after injection of skeletal muscle Ag and adjuvant that is characterized by necrosis of muscle fibers associated with infiltrating mononuclear cells. In the present study, an immunohistologic analysis was performed to examine the phenotype of these infiltrating cells and to determine changes in cell-surface Ag expression in involved muscle. The predominant cells infiltrating muscle after induction of experimental autoimmune myositis (EAM) were found to be Mac-1+/I-A+ macrophages, representing 80 to 90% of all infiltrating cells, and CD4+ T lymphocytes, representing 10 to 15% of all infiltrating cells. Few CD8+ T cells, and no B cells, were seen in the involved muscles. Interestingly, endothelial cells in involved muscles were also noted to express class II MHC Ag. Aberrant I-A Ag expression was not observed on endothelial cells in other tissues examined, including kidney, liver, cardiac muscle, and lung. I-A Ag expression appeared to correlate with susceptibility to disease in that muscle endothelial cells remained negative after attempts to induce EAM in a nonsusceptible strain. Together, the data suggest that aberrant organ-specific class II MHC Ag expression and a response by CD4+ T cells may be pathogenetically involved in the muscle injury of EAM. In addition, the predominance of infiltrating macrophages suggests that these recruited cells may also be important in the immune-mediated muscle damage.
Mechanism of lysis by large granular lymphocyte granule cytolysin: generation of a stable cytolysin-RBC intermediate.
Authors: Kuta A E , Reynolds C R , Henkart P A 
Published: December 2022

Abstract
The effect of ionic strength and pH on the hemolytic activity of large granular lymphocyte granule cytolysin was examined in detail. Cytolysin-mediated lysis of RBC was inhibited by either low ionic strength or low pH. Under these conditions a nonlytic cytolysin-RBC intermediate was formed as revealed by hemolysis when cytolysin pretreated cells were washed and resuspended at physiologic ionic strength and pH. Formation of the cytolysin-RBC intermediate at low ionic strength (250 mM sucrose), pH 7.3, required greater than 0.1 mM calcium. In contrast, formation of the intermediate at physiologic ionic strength (150 mM NaCl), pH 6.0, was calcium independent. Both types of intermediates were stable at 37 degrees C and required calcium to induce subsequent lysis. The degree of lysis of the intermediate generated at low ionic strength was similar to that measured under standard conditions with the use of either whole granule preparations or purified cytolysin. However, lysis of intermediates formed at pH 6.0 was much less efficient. Our data indicate that a stable cytolysin-RBC intermediate can be formed in which cytolysin is present in an unreactive state on the RBC surface; under conditions of physiologic ionic strength and calcium concentrations this intermediate rapidly lyses.
Vaccination against murine cutaneous leishmaniasis by using Leishmania major antigen/liposomes. Optimization and assessment of the requirement for intravenous immunization.
Authors: Kahl L P , Scott C A , Lelchuk R , Gregoriadis G , Liew F Y 
Published: December 2022

Abstract
Efficacy of vaccination against cutaneous leishmaniasis in highly susceptible BALB/c mice was assessed comparatively by using radiation-attenuated promastigotes and colloidal Ag mixtures generated from a mixed Leishmania major (LV39) isolate (SLV39) and from a virulent cloned line (SVJ2) derived from the Jericho 2 L. major isolate. Dehydration-rehydration vesicle (DRV) liposomes were used as adjuvants. In optimization experiments phospholipid composition of DRV was varied, and the distearoyl derivative (DSPC) (liquid-crystalline phase transition temperature (Tc) 54 degrees C) of egg lecithin L-alpha-phosphatidylcholine was found to be superior to the dipalmitoyl derivative (DPPC, Tc 41.5 degrees C) and underivatized L-alpha-phosphatidylcholine (Tc -10 degrees C). The criteria studied were in vivo priming for a secondary in vitro proliferative response and the prepatency of lesion onset after L. major challenge of mice immunized once i.v. A single s.c. immunization with SLV39 either free or entrapped within DSPC liposomes primed spleen cells to produce significant levels of IL-3 when stimulated with SLV39 in vitro. In contrast, the i.v. route of immunization with the same Ag preparations led to little or no IL-3 production by the spleen cells. Despite development of significant T cell activation, both SLV39 and SVJ2 administered s.c., either free or entrapped within liposomes, were not protective. However, i.v. immunization four times with SVJ2 entrapped within DSPC liposomes induced a level of resistance comparable with that of 2 x 10(7) gamma-irradiated promastigotes in the stringent BALB/c L. major model. Although significant, protection conferred after i.v. immunization with SLV39/DSPC liposomes was less effective. These data therefore show that DSPC/DRV liposomes, although a good adjuvant for inducing protective immunity to cutaneous leishmaniasis, are not able to overcome the requirement for an i.v. route of immunization with the leishmanial Ag preparation. Additionally, they demonstrate a correlation between IL-3 secretion and non-protection. They also suggest that SVJ2 represents a better source of protective Ag than SLV39.
Characterization of a helper T lymphocyte defect in vitamin A-deficient mice.
Authors: Carman J A , Smith S M , Hayes C E 
Published: December 2022

Abstract
Vitamin A-deficient mice exhibited sharply decreased IgG1 responses to protein Ag in vivo and in vitro. We traced the cellular basis for these impaired responses to a functional defect in A-deficient Th. Ag-presenting cells and B cells from A-deficient mice showed no functional defects. The A-deficient T cells proliferated normally in response to Ag but failed to provide the B cell stimulus for Ag-specific IgG1 responses. The A-deficient mice had fewer Th by limiting dilution analysis, and retinyl acetate supplementation in vitro restored Th frequency to control levels. Because added retinyl acetate reversed the Th functional block, these vitamin A-deficient T cells must be primarily defective in activation, not in establishment of immunologic memory.
A synergistic interaction of IL-6 and IL-1 mediates the thymocyte-stimulating activity produced by recombinant IL-1-stimulated fibroblasts.
Authors: Elias J A , Trinchieri G , Beck J M , Simon P L , Sehgal P B , May L T , Kern J A 
Published: December 2022

Abstract
We characterized the ability of normal human lung fibroblasts to elaborate thymocyte-stimulating activity, spontaneously, and in response to rIL-1. Supernatants from unstimulated fibroblasts did not contain thymocyte-stimulating activity, whereas supernatants from fibroblasts incubated with rIL-1 alpha or rIL-1 beta contained more thymocyte-stimulating activity than could be accounted for by passively transferred rIL-1 alone. This heightened thymocyte-stimulating activity was mediated by fibroblast-derived IL-6 inasmuch as it was neutralized by anti-serum against human rIL-6, and rIL-1-stimulated fibroblasts to accumulate messenger RNA for IL-6 and produce soluble IL-6 protein. However, IL-6 alone could not account for the intensity of this effect because rIL-6 only weakly stimulated thymocyte proliferation. In addition, antisera against the rIL-1 moiety that was used to prepare the supernatant had different effects on supernatants that contained and did not contain active IL-6. In the presence of IL-6 these antisera caused a greater decrease in thymocyte-stimulating activity than could be accounted for by passively transferred rIL-1 alone. When the IL-6 was neutralized the remaining thymocyte-stimulating activity could be quantitatively accounted for and neutralized by antisera against the rIL-1 that was passively transferred. Furthermore, rIL-6 and rIL-1 (alpha or beta) synergized in stimulating thymocyte proliferation. Thus, rIL-1 stimulates fibroblasts to produce a thymocyte-stimulating activity that is largely mediated by a synergistic interaction of fibroblast-derived IL-6 and IL-1. These findings suggest that fibroblast production of IL-6 may mediate or amplify some of the tissue effects of IL-1. In addition they suggest that biologic effects previously attributed to IL-1 may be due to IL-6 alone or the concerted action of IL-1 and IL-6.
IL-1 stimulates IL-6 production in endothelial cells.
Authors: Sironi M , Breviario F , Proserpio P , Biondi A , Vecchi A , Van Damme J , Dejana E , Mantovani A 
Published: December 2022

Abstract
Leukocytes and vascular cells interact closely in inflammation and immunity and lymphokines are important mediators of this interaction. The present study was designed to define the possible role of IL-6 as a communication signal between vascular and immunocompetent cells. IL-6 was measured as hybridoma growth factor (HGF) on the 7TD1 cell line in the supernatants of human endothelial cells (HEC). HEC released appreciable levels of HGF activity in the absence of deliberate stimulation. In vitro exposure to recombinant IL-1 beta markedly increased (usually 10 to 15-fold) HGF production by HEC. Optimal stimulation was observed with 0.1 to 50 U/ml for 4 to 20 h of incubation. Human and murine rIL-1 alpha stimulated HGF production in HEC. Anti-IL-6 antibodies inhibited the HGF activity of the HEC supernatants, thus confirming, together with the cytokine specificity of the assay, the nature of HEC-produced cytokine. IL-1-treated HEC expressed high levels of IL-6 mRNA as detected by Northern blot analysis. Inasmuch as IL-1 elicits a complex series of changes in HEC, it was important to assess whether IL-6, produced after exposure to IL-1, modified HEC function. Natural or rIL-6 did not affect the functional status of HEC as assessed by proliferative capacity, production of procoagulant activity and prostacyclin, ability to induce adhesion of polymorphonuclear leukocytes. The capacity to produce IL-6 may represent an important mechanism by which endothelial cells participate in inflammatory and immune reactions.
Immunostimulation of C3H/HeJ lymphoid cells by R-chemotype lipopolysaccharide preparations.
Authors: Flebbe L , Vukajlovich S W , Morrison D C 
Published: December 2022

Abstract
Splenocytes from the C3H/HeJ and C57BL/10ScN (nu/nu) inbred mouse strains have been characterized by a genetic defect in their capacity to proliferate in response to purified protein-free LPS preparations. In this manuscript we provide experimental evidence to support the concept that the refractory state of B cells from endotoxin-unresponsive mice to mitogenic stimulation by LPS does not extend to R-chemotype LPS isolated from a variety of rough strains of Salmonella or Escherichia coli. We present several lines of evidence to suggest that the observed mitogenic activity is not the result of contamination of LPS with lipid A-associated proteins. The mitogenic activity of LPS extracted from rough strain mutant bacteria (R-LPS) appears to be dependent upon a structural requirement of the LPS in which the 2-keto-3-deoxyoctulosonate linkage of lipid A with core oligosaccharides is intact. Both alkaline and acid hydrolysis of R-LPS abrogates mitogenic activity in C3H/HeJ splenocytes; only the former is effective in reducing activity of the same LPS preparations in histocompatible normal splenocytes. Finally, we have found that the addition of either polymyxin B or S-chemotype LPS to R-LPS-stimulated C3H/HeJ splenocytes has only minimal effects on the mitogenic activity of the latter. These combined data would indicate that the concept of LPS-unresponsiveness of the C3H/HeJ and C57B1/10ScN inbred mouse strains is not necessarily applicable to all protein-free LPS preparations.
Structural requirements for IgM assembly and cytolytic activity. Effects of mutations in the oligosaccharide acceptor site at Asn402.
Authors: Muraoka S , Shulman M J 
Published: December 2022

Abstract
Glycosylation of IgG occurs at asparagine 297 of the gamma H chain and is necessary for the normal capacity of IgG to activate the classical pathway of complement-dependent cytolysis. IgM is glycosylated at five sites in the constant region of the mu H chain, of which glycosylation at asparagine 402 seems analogous to the glycosylation of IgG. In order to assess the importance of glycosylation at asparagine 402 for IgM cytolytic activity, we have used site-directed mutagenesis to produce IgM which is not glycosylated at this position. In particular we have tested the effects of substituting Gln for Asn 402 and Thr-Gly for Gly 403-Thr 404 in the third constant region domain. We tested the effects of these substitutions by expressing the mutant mu genes in hybridoma cells which produce the hapten-specific kappa-chain. The normal mu-chain is glycosylated at Asn 402, and, as expected, these mutations appear to abrogate glycosylation of the mutant mu-chains at position 402 and do not affect the hapten affinity of the IgM. However, both of these mutations cause the increased production of monomeric rather than polymeric IgM: the ratio of monomeric to polymeric IgM is 0.21, 3.5, and 10.3 for wild-type IgM, IgM-Gln 402, and IgM-Thr 403-Gly 404, respectively. The wild-type and mutant polymeric IgM preparations were compared for their capacity to promote complement-dependent cytolysis: IgM-Gln 402 and IgM-Thr 403-Gly 404 have approximately 31% and 4%, respectively, of the capacity of wild-type IgM.
Lymphokine-activated tumor inhibition in mice. Ability of a nonapeptide of the human IL-1 beta to recruit anti-tumor reactivity in recipient mice.
Authors: Forni G , Musso T , Jemma C , Boraschi D , Tagliabue A , Giovarelli M 
Published: December 2022

Abstract
The ability of the VQGEESNDK synthetic peptide corresponding to fragment 163-171 of human IL-1 beta to trigger lymphokine-activated tumor inhibition (LATI) of a poorly immunogenic fibrosarcoma (CE-2) of BALB/c mice was compared to that of the whole IL-1 beta. Neither molecule inhibits in vitro proliferation of CE-2 cells. Administration at the tumor challenge site for 10 days of daily injections of 50 micrograms of peptide 163-171 induce a consistent, although limited, inhibition of tumor growth, whereas similar injections of 1 pg of IL-1 beta induced a more marked LATI. However, strong LATI was elicited when these injections were performed in mice challenged with tumor cells admixed at 1/10 cell ratio with nonreactive lymphocytes from CE-2-bearing mice. The L3T4+ lymphocyte subset is mainly responsible for this enhancement. This reaction is abolished when recipient mice are sub-lethally irradiated, treated with cyclosporin A, or when the reactivity of L3T4+ and asialo GM1+ cells is suppressed. A similarly efficient LATI is found on combining the daily peptide injections with that of 10 U of IL-2. LATI stemming from this association, too, is abolished when mice are irradiated or treated with anti-L3T4 antibody, whereas it is not affected by cyclosporin A or anti-asialo GM1 antibody. Finally, a tumor-specific immune memory is acquired by about 50% of mice after LATI induced by IL-1 beta or 163-171 peptide alone and by about 80% of mice after LATI induced by peptide and lymphocytes from tumor-bearing mice or peptide and IL-2. These findings could lead to the building of a molecularly defined system to induce efficient immune recognition of tumor cells by using a peptide that does not cause any of the several inflammation-associated changes induced by the whole IL-1 beta.
Role of the maleyl-albumin receptor in activation of murine peritoneal macrophages in vitro.
Authors: Haberland M E , Tannenbaum C S , Williams R E , Adams D O , Hamilton T A 
Published: December 2022

Abstract
It has been previously demonstrated that maley-lated-BSA (maleyl-albumin) induces functional activation in murine peritoneal macrophages. Furthermore, maleyl-albumin has been shown to interact with two distinct sites on human monocytes; one site is the scavenger receptor, a 260-kDa oligomeric protein which recognizes modified forms of low density lipoprotein (LDL), and the second is a lower affinity site which has yet to be structurally characterized. In the present study, we wished to quantitatively assess the number and character of maleyl-albumin-binding sites on murine peritoneal macrophages and to determine which site or sites are involved in signaling the macrophage to undergo extensive functional development. Binding studies. demonstrate at least two distinct receptors for maleyl-albumin on murine peritoneal macrophages. Scatchard analyses of the binding isotherms reveal two sites characterized by dissociation constants (Kd) of 17.6 nM and 4.9 microM and maximal binding of 1.2 x 10(5) and 1 x 10(6) sites/cell, respectively. The contribution of the scavenger receptor, determined by binding analyses of malondialdehyde-LDL, is described by two sites with Kd of 39.4 pM and 9.6 nM, and maximal binding of 2.7 x 10(3) and 1.9 x 10(4) sites/cell, respectively. Maleyl-albumin blocks binding of malondialdehyde-LDL, whereas modified LDL fails to inhibit binding of maleyl-albumin. Maleyl-albumin, at concentrations producing lower affinity binding, stimulates tumor cytolysis, expression of mRNA encoding TNF, and suppression of INF-gamma-induced expression of Ia Ag. Malondialdehyde-LDL fails to elicit these responses. We conclude that macrophage activation produced by maleyl-albumin is mediated by interaction with the low affinity, high capacity binding site for maleyl-albumin rather than the scavenger receptor.
Activation of cloned human natural killer cells via Fc gamma RIII.
Authors: Werfel T , Uciechowski P , Tetteroo P A , Kurrle R , Deicher H , Schmidt R E 
Published: December 2022

Abstract
The Fc gamma RIII (CD16) Ag on human NK cells involved in antibody-dependent cellular cytotoxicity has been demonstrated to be an important activation structure. The present studies were carried out to further characterize the functional role of the CD16 Ag and the mechanisms whereby cytotoxicity is activated by using human NK clones. In phenotypic studies Fc gamma RIII was found to be expressed heterogeneously on various human cloned NK cells. Expression on CD3- and CD3+ clones varied with the donor and mAb used for detection. Functional data demonstrated that cytotoxicity against NK-resistant target cells can be induced in CD3-CD16+ NK clones and CD3+CD16+ clones with NK activity when various CD16 mAb were used. CD16 antibodies but not reactive isotype control antibodies induced cytotoxicity. In contrast to complete CD16 antibodies F(ab')2 fragments were not able to activate the cytotoxic mechanism. Both an antibody against FcR on the target cell (Fc gamma RII) and a CD11a antibody blocked induction of cytotoxicity. These results suggest that three steps are critical for activation of CD16+ cells via Fc gamma RIII: 1) specific binding of CD16 antibodies to Fc gamma RIII on effector cells irrespective of the epitope recognized; 2) cross-linking of effector cell CD16 Ag through binding of the Fc site of CD16 antibodies via corresponding FcR on the target cell membrane; and 3) interaction of CD11a/18 molecules with the target cell membrane.
Human newborn natural killer cell responses to activation by monoclonal antibodies. Effect of culture with herpes simplex virus.
Authors: Hayward A , Laszlo M , Vafai A 
Published: December 2022

Abstract
Deficient responses by NK cells may contribute to the susceptibility of human newborns to severe HSV infections. Furthermore, HSV disseminates widely during neonatal infection and may also infect and interfere with the function of blood mononuclear cells (MNC). To determine whether the function of newborn NK cells would be affected by contact with HSV, and whether newborn NK cells might be permissive for HSV replication, newborn MNC were cultured with HSV in vitro for 3 days. Before culture, the intracellular calcium mobilization in newborn NK cells induced by mAb to CD2 and CD16 did not differ from that of adult NK cells. This result argues against immaturity of an early NK cell activation event in human newborns. After culture with HSV the Ca2+ flux response was unaffected by lysis of K562 targets by newborn NK cells and NK-dependent suppression of HSV replication in fibroblasts were preserved or increased. Incorporation of thymidine by NKH-1 cells following stimulation with PHA and IL-2 was not suppressed. NK cells recovered from these cultures did not contain infectious HSV and synthesis of HSV-specific proteins was not detected by immunoprecipitation although HSV genome was detected by DNA hybridization. Our results extend the in vitro model stimulation systems in which newborn NK cells respond positively to include triggering through the CD2 Ag, cross-linking of cell surface CD 16 Ag and response to a pathogen, HSV.