bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antigen-induced Ca2+ signaling and desensitization in B cells.
Authors: Lazarus A H , Mills G B , Delovitch T L 
Published: December 2022

Abstract
Cross-linking of B cell surface Ig (sIg) by anti-Ig results in transmembrane signaling. However, the capacity of a thymus-dependent (TD) Ag to mediate B cell signal transduction has been less well documented. Therefore, we examined Ag-induced intracellular free calcium concentration [( Ca2+]) in B cells by using TD Ag that would be expected to either cross-link or not cross-link sIgM and/or induce the coupling of sIgM to FcR. Stimulation of mouse TA3 hybridoma B cell transfectants that express the SP6 anti-TNP specific sIgM with either TNP-OVA or anti-IgM antibodies resulted in a maximal fourfold increase in [Ca2+]i. The net increase in [Ca2+]i in response to TNP-OVA was dependent upon both the Ag dose and the TNP:OVA molar ratio. Because occupancy of several cell-surface receptor types leads to a loss of response to subsequent stimulation by ligand (homologous desensitization), we examined the ability of Ag to induce homologous desensitization of sIgM in these B cells. TNP1-OVA at all concentrations tested (up to 500 micrograms/ml) did not lead to any change in [Ca2+]i or desensitization. Cross-linking of TNP1-OVA (10 micrograms/ml) with F(ab')2 of anti-OVA antibody induced both a rise in [Ca2+]i and homologous desensitization of sIg, suggesting that cross-linking of sIgM by Ag is sufficient to induce both these processes. TNP6-OVA at a concentration of 10 micrograms/ml induced changes in [Ca2+]i and partially desensitized TNP-specific B cells to stimulation by anti-IgM. Interestingly, a high dose (180 micrograms/ml) of TNP6-OVA stimulated minimal changes in [Ca2+]i yet did not lead to desensitization. However, cross-linking of TNP6-OVA at this high dose with F(ab')2 of rabbit anti-OVA elevated [Ca2+]i and elicited partial desensitization. Complete desensitization of sIgM by Ag was achieved when intact (Fc-containing) anti-OVA antibody was used, suggesting that the FcR can play a role in desensitization. Ag- and antibody-mediated desensitization was not caused by steric hindrance of sIg. Thus, we have observed two forms of Ag-induced desensitization of sIgM, both of which involve sIg cross-linking and one of which is mediated by the physiologic coupling of sIg to FcR.
Orally inducible immune unresponsiveness is abrogated by IFN-gamma treatment.
Authors: Zhang Z Y , Michael J G 
Published: December 2022

Abstract
The role of murine epithelial cells from small intestine (IEC) in orally induced immune unresponsiveness has been investigated. Murine IEC were shown to express a relatively low level of class II MHC Ag and were incapable of presenting BSA to Ag-specific Th cells. IFN-gamma treatment of the animals dramatically enhanced expression of class II MHC Ag by IEC enabling Ag presentation to Th cells. Ag-presenting function of IEC after IFN-gamma treatment was not affected by IEC panning on anti-IgG or anti-MAC-1-coated plates but it was blocked by a class II MHC-specific mAb. IFN-gamma-treated mice were responsive to parenteral BSA challenge after oral administration of the Ag, whereas untreated mice were immunosuppressed. Our data support the concept that poor expression of class II MHC Ag on IEC contributes to immunosuppression induced by oral administration of a protein Ag.
Decreased HLA-DR antigen expression on monocytes causes impaired suppressor cell activity in multiple sclerosis.
Authors: Baxevanis C N , Reclos G J , Papamichail M 
Published: December 2022

Abstract
Mitogen-induced Ts cell activity and (DR) expression on monocytes have recently been shown to be reduced in patients with multiple sclerosis (MS). In our study, T cells were cultured with autologous monocytes in the presence of Con A for 6 days (primary cultures). At the end of the culture T cells were isolated and were 1) tested for surface DR expression and 2) treated with mitomycin C and placed in a secondary culture of allogeneic responder cells and Con A, to test their suppressor function. Treatment of monocytes of the primary culture with an anti-HLA-DR antibody abolished the expression of DR Ag on the T cells as well as their ability to function as Ts cells in the secondary culture. Monocytes from patients with active MS expressed low levels of surface DR Ag and induced reduced amounts of DR Ag on the surface of autologous T cells in primary cultures, which in turn expressed deficient suppressor function when placed in secondary cultures. In contrast, monocytes obtained from patients with inactive disease expressed higher levels of DR and induced higher amounts of DR Ag on autologous T cells, which expressed normal suppressor function. We conclude that the deficient expression of DR Ag on MS monocytes causes reduced suppressor function in activated autologous T cells and may be a primary abnormality in the immunopathogenesis of MS.
IL-6 stimulates osteoclast-like multinucleated cell formation in long term human marrow cultures by inducing IL-1 release.
Authors: Kurihara N , Bertolini D , Suda T , Akiyama Y , Roodman G D 
Published: December 2022

Abstract
IL-6 enhances the differentiation of pluripotent hematopoietic stem cells but predominantly affects the differentiation of hematopoietic cells in the granulocyte-macrophage lineage. We have previously shown that multinucleated cells (MNC) with many features of the osteoclast phenotype form in long term human marrow cultures. Addition of rhIL-6 (10 to 100 pg/ml) to these cultures significantly increased MNC formation, with greater than 80% of the MNC expressing an Ag that cross-reacts with the mAb 23c6. This antibody preferentially binds to osteoclasts. rhIL-6 did not enhance MNC formation in marrow cultures treated with 1,25 dihydroxyvitamin D3, a potent stimulator of MNC formation, but significantly increased the percentage of MNC that cross-reacted with the 23c6 mAb. Addition of antihuman IL-1 to cultures treated with rhIL-6 totally inhibited the increase in MNC formation stimulated by rhIL-6. In contrast, anti-IL-1 did not affect MNC formation stimulated by 1,25 dihydroxyvitamin D3. Further, conditioned media from marrow cultures exposed to rhIL-6 contained elevated levels of IL-1 beta (500 pg/ml compared to 23 pg/ml in control cultures 15 h after IL-6 addition). These results suggest that the capacity of rhIL-6 to stimulate formation of MNC which cross-react with 23c6 is mediated by induction of release of IL-1 beta.
Regulation of arachidonic acid release in mouse peritoneal macrophages. The role of extracellular calcium and protein kinase C.
Authors: Balsinde J , Fernández B , Diez E 
Published: December 2022

Abstract
Primary cultures of [3H]arachidonic acid-prelabeled mouse peritoneal macrophages were stimulated with the physiologic agonists zymosan and Con A. The cells released a large quantity of labeled compounds into the extracellular medium. When the cells were preincubated for 10 min with PMA at concentrations from 10 to 1000 ng/ml, zymosan- and Con A-stimulated compound release was greatly enhanced. PMA also potentiated arachidonic acid release when cells were stimulated with the calcium ionophore A23187. However, under the same conditions, PMA treatment blocked agonist- and ionophore-mediated phosphoinositide hydrolysis in cells prelabeled with [3H]inositol. Thus, PMA treatment appears to have dissociated agonist-induced arachidonic acid liberation (index of phospholipase A2) from phosphoinositide hydrolysis (index of phospholipase C), suggesting that these two coupling processes can occur in a parallel and independent manner in mouse peritoneal macrophages. Furthermore, the ligand-induced arachidonic acid release from PMA-treated macrophages was shown to be directly dependent on the extracellular calcium concentration. Considering that in PMA-pretreated cells, receptor-mediated phosphoinositide breakdown and intracellular calcium mobilization were abolished, our data suggest that the extracellular calcium influx that takes place after receptor-ligand interaction may be a required event for arachidonic acid mobilization in mouse peritoneal macrophages.
Activation of mouse peritoneal macrophages during infection with Salmonella typhimurium does not result in enhanced intracellular killing.
Authors: Langermans J A , van der Hulst M E , Nibbering P H , van Furth R 
Published: December 2022

Abstract
Our study was performed to investigate whether macrophages become activated during an infection with Salmonella typhimurium and, if so, whether these activated macrophages kill S. typhimurium faster than resident macrophages. Mice received i.v. injections with a sublethal number of S. typhimurium; on about day 12 of the infection the numbers of bacteria in the liver and the spleen were maximal. During the infection, activation of peritoneal macrophages could be demonstrated on the basis of three criteria, i.e., the ability to inhibit the proliferation of Toxoplasma gondii, an enhanced production of H2O2 and an increased expression of Ia Ag. The rate of in vitro intracellular killing of S. typhimurium by these activated macrophages was not increased compared to that for resident macrophages. To determine the growth of S. typhimurium in activated mice a nalidixic acid-resistant mutant strain, called S. typhimurium 510R, was used. The net growth rates of the mutant S. typhimurium 510R in the spleen of S. typhimurium 510-activated and normal mice were similar. However, in the liver of S. typhimurium 510-activated mice the number of S. typhimurium 510R did not change during 3 to 48 h after injection. The role of specific antibodies during the initial phase of the infection was negligible, because only low levels of antibodies were detected during the first 15 days of infection and the growth rates of S. typhimurium 510 in the spleen and liver of mice with high titers of antibodies were not significantly different from the rates in normal mice. The results of this study demonstrate that although macrophages become activated during an infection with S. typhimurium, these cells do not display an enhanced bactericidal activity in vitro and in vivo no significant effect on the growth rate of S. typhimurium in the spleen and a bacteriostatic effect in the liver is found. Hence macrophage activation is probably not very important in the host defense against S. typhimurium.
Recombinant IL-2 therapy reverses diminished granulomatous responsiveness in anti-L3T4-treated, Schistosoma mansoni-infected mice.
Authors: Mathew R C , Ragheb S , Boros D L 
Published: December 2022

Abstract
We have previously shown, that anti-L3T4 mAb treatment strongly suppressed granuloma formation in the liver, and IL-2 production in the spleen of Schistosoma mansoni-infected mice. In the present study the dynamics of IL-2 production was delineated during the infection, and the effect of rIL-2 treatment on granulomatous responsiveness was examined. IL-2 production in soluble egg Ag-stimulated spleen cells of mice was detectable at 6, peaked at 8 and waned by 20 wk of the infection. In contrast, Con A stimulus elicited high levels of IL-2 production by 8 wk which remained nearly unchanged throughout the infection. Administration of rIL-2 to acutely infected, anti-L3T4 mAb-treated, or chronically infected mice reversed the diminished or modulated granulomatous responses without restoring the ability for endogenous IL-2 production. Transfer of spleen cells of anti-L3T4 mAb-treated, chronically infected mice did not indicate a role for Ts cells in the impaired production of IL-2 in recipients. These data suggest that lack of IL-2 production can play an important role in the immunoregulation of the granulomatous response.
Mechanisms of anti-CD4-mediated depletion and immunotherapy. A study using a set of chimeric anti-CD4 antibodies.
Authors: Alters S E , Sakai K , Steinman L , Oi V T 
Published: December 2022

Abstract
A family of rat-mouse chimeric anti-murine CD4 antibodies was used to study the mechanisms of anti-CD4-mediated depletion and immunotherapy. The chimeric antibodies retain identical affinity and specificity as the therapeutically effective prototype antibody, rat GK1.5, but are of different mouse isotypes. GK1.5 gamma 1, GK1.5 gamma 2a, and GK1.5 gamma 2b are significantly more effective at CD4+ cell depletion than rat GK1.5 when low doses of antibody are administered. In contrast, no depletion is seen with GK1.5 gamma 3 at any dose. Depletion of CD4+ cells in vivo is not correlated with either the ability of the antibody to mediate C-dependent cytotoxicity or antibody-dependent cell-mediated cytotoxicity in vitro, implying that additional antibody-mediated cytotoxic mechanisms occur in vivo. The chimeric antibodies were used to investigate the mechanism of GK1.5-mediated immunotherapy in a prototypic model of T cell-mediated autoimmunity, experimental allergic encephalomyelitis. Mice treated with a single dose of 100 micrograms of either GK1.5, GK1.5 gamma 1, or GK1.5 gamma 2a showed significant recovery within 72 h. In contrast, mice treated with 100 micrograms of GK1.5 gamma 3 showed only marginal improvement within the first 72 h and regressed within 5 days of treatment initiation. These data suggest that anti-CD4-mediated immunotherapy of murine experimental allergic encephalomyelitis is correlated with depletion of CD4+ cells.
A study of in vivo immune complex formation and clearance in man.
Authors: Davies K A , Hird V , Stewart S , Sivolapenko G B , Jose P , Epenetos A A , Walport M J 
Published: December 2022

Abstract
C and CR1 have been shown to participate in the clearance of injected, preformed, immune complexes in humans and in non-human primates. Their role in the physiologic disposal of immune complexes formed in vivo in humans was investigated in three patients receiving radioimmunotherapy for ovarian carcinoma. On day 0 each patient received, by intraperitoneal injection, 10 mg of 131I-mouse anti-tumor mAb (10 mCi/mg). On days 1 and 2, 18 mg of trace-labeled, 125I-human anti-mouse IgG was administered by i.v. infusion over 15 min, to accelerate the clearance of the 131I-anti-tumor antibody from the circulation and reduce the radiation dose to the marrow. Sequential blood samples were obtained after the injection of the second (anti-mouse) antibody, to monitor clearance. Immune complexes (shown by sucrose gradient centrifugation to be 19 to 40 S in size) formed within 5 min, and were cleared with a half-life of 11 +/- 1.7 min in the liver. Complexes were measured by 4% polyethylene glycol precipitation, and by solid phase C3d- and C1q-binding assays. Between 8 and 11% of the total available complexed material bound to CR1 on E. Peak binding of immune complexes to red cells occurred 10 min after the maximal complex load was detected by precipitation with polyethylene glycol. At that time, immune complexes bound to E constituted one-fifth of the total circulating pool of complexes. Coincident with immune complex formation and clearance, a 47% fall in serum C4, C3, and CH50 was measured, with the deposition of up to 1230 molecules of C4, and 2590 molecules of C3 on the surface of red cells. During 20 min after immune complex formation there was a mean loss of 32% of erythrocyte CR1. The changes in complement and CR1 on E and in serum observed in these patients resembled those seen in patients with SLE: i.e., a reduction in CR1 and an increase in C3 and C4 on E, and reduced serum C.
Monoclonal antibodies directed against the galactose-binding lectin of Entamoeba histolytica enhance adherence.
Authors: Petri W A , Snodgrass T L , Jackson T F , Gathiram V , Simjee A E , Chadee K , Chapman M D 
Published: December 2022

Abstract
The Entamoeba histolytica galactose-binding lectin is a surface glycoprotein composed of 170- and 35-kDa subunits. Inhibition of this lectin with galactose or anti-170 kDa subunit polyclonal antibody blocks amebic adherence to target cells and colonic mucin glycoproteins. We describe the properties of 10 mAb with specificity for the 170-kDa subunit. Based on competitive binding studies, six nonoverlapping antigenic determinants on the lectin were identified. The effect of the mAb on adherence of amebic trophozoites to both Chinese hamster ovary (CHO) cells and human colonic mucins was measured. Antilectin antibodies directed against epitopes 1 and 2 enhanced adherence, with the number of amebae having at least three adherent CHO cells increasing with the addition of epitope 1 mAb from 26 +/- 9 to 88 +/- 2% and the binding of colonic mucins increasing from 34 +/- 1 to 164 +/- 3 pg/10(5) amebae. Antibody-enhanced adherence remained 90 to 100% galactose inhibitable, occurred at 4 degrees C and was not Fc mediated. Univalent Fab fragments of epitope 1 mAb augmented mucin binding by 238% and CHO cell adherence by 338%. The binding of purified lectin to CHO cells was increased from 1.1 +/- 0.1 to 2.4 +/- 0.3 ng/10(3) CHO cells by mAb directed to epitope 1, demonstrating that enhanced adherence was due to direct activation of the lectin. mAb to epitope 3 bound to the lectin only upon its solubilization from the membrane and had no effect on adherence. Adherence to CHO cells and mucins was inhibited from 50 to 75% by mAb to epitopes 4 and 5; epitope 6 mAb inhibited amebic adherence to CHO cells but not mucins. The pooled sera from 10 patients with amebic liver abscess blocked the binding to the 170-kDa subunit of mAb directed to all six epitopes. Striking individual variations in the effects of immune sera on adherence were observed. Although the sera of all 44 South African patients with amebic liver abscess had high titer anti-lectin antibodies, 16 patients' sera significantly (more than 3 SEM) enhanced adherence whereas 25 patients' sera significantly inhibited adherence. Antilectin antibodies exert profound functional effects on the interaction of E. histolytica with target cells and human colonic mucins. Exploration of the clinical consequences of adherence-enhancing and inhibitory antibody responses may give insight into the role of antilectin antibodies in immunity to invasive amebiasis.
Expression of the human leukocyte adhesion molecule, LAM1. Identity with the TQ1 and Leu-8 differentiation antigens.
Authors: Tedder T F , Penta A C , Levine H B , Freedman A S 
Published: December 2022

Abstract
The LAM1 molecule is a member of the new family of cellular adhesion/homing molecules that contain a lectin-like domain at their amino-terminal end followed by an epidermal growth factor-like domain and short consensus repeat units like those found in C3/C4 binding proteins. Two mAb that react with the leukocyte adhesion molecule 1 (LAM1) were produced and used to examine the cell-surface expression of LAM1. The anti-LAM1 antibodies were reactive with the majority of blood lymphocytes, NK cells, neutrophils, and monocytes. LAM1 was also expressed by subpopulations of phenotypically immature and mature thymocytes. Blood lymphocytes rapidly modulated LAM1 from the cell surface during PMA exposure for 60 min. Coordinate with the loss of LAM1 from the cell surface, PMA-treated lymphocytes lost the ability to bind to lymph node high endothelial venules, indicating that expression of LAM1 may play a role in lymphocyte homing. Mitogen stimulation of blood T and B lymphocytes also resulted in decreased LAM1 expression, but at a slower rate. LAM1 was only weakly expressed by a minority of spleen lymphocytes. However, culturing spleen lymphocytes in media alone resulted in increased expression of LAM1 by a subpopulation of the cells (40 to 60%). Concomitant mitogen stimulation of spleen lymphocytes resulted initially in down-regulation of LAM1 expression followed by increased expression of LAM1 and then subsequent loss of LAM1 from the cell surface. The pattern of anti-LAM1 antibody reactivity was identical to that reported for the TQ1 and Leu-8 antibodies, and all of these antibodies reacted with cells transfected with the LAM1 cDNA. Thus, LAM1 is broadly expressed by leukocytes, and binding of LAM1 may participate in the process of leukocyte extravasation into lymphoid organs or sites of acute inflammation with subsequent loss of LAM1 from the cell surface.
Protease inhibitors block the macrophage-mediated inhibition of tumor cell mitochondrial respiration.
Authors: Kilbourn R , Lopez-Berestein G 
Published: December 2022

Abstract
The antitumor activity of activated macrophages toward tumor cells, in vitro, appears to involve the production of toxic nitrogen intermediates. These intermediates, particularly nitric oxide, have been shown to cause the inhibition of cell division and to decrease cellular respiration by inhibiting electron transport. We studied the effects of proteolytic inhibitors on macrophage-mediated inhibition of L1210 tumor cell respiration and DNA synthesis, and found that chloromethyl ketone derivatives, which covalently modify serine proteases, can block macrophage cytotoxicity. Furthermore, these inhibitors decrease nitrite production by activated macrophages suggesting that the mechanism of action involves the inhibition of nitric oxide production.
Modulation of lymphokine release and cytolytic activities by activating peripheral blood lymphocytes via CD2.
Authors: Valentin H , Groux H , Gelin C , Chretien I , Bernard A 
Published: December 2022

Abstract
We had previously shown that the signal of activation delivered via CD2 varies according to the mitogenic pair of CD2 mAb used. We had selected two typical mAb pairs, D66 + T11(1) and GT2 + T11(1), the former delivering the "richest" signal, the latter the poorest. Here we analyzed the cytolytic activities generated within PBL-stimulated by these two pairs. When purified CD2+,3- cells were cultured with either one of these two pairs, no significant lymphokine-activated killer (LAK) activity--namely the activity exerted on NK-resistant malignant cell lines or fresh tumor cells--was detected, thereby demonstrating the inability of CD2 mAb pairs to directly trigger the LAK precursors. By contrast, when purified CD2+,3+ cells were cultured, only D66 + T11(1) was able to trigger a potent CTL activity, as judged by targeting their activity, at the effector phase, with a bridging CD3 mAb on a FcR+ target cell or by using heteroaggregates on FcR- malignant cells. When whole PBL were used, a similar and moderate LAK activity was generated after culture with either one of the 2 CD2 mAb pairs. This, in fact, masked quite different events. The amounts of endogeneous IL-2 released in PBL cultures with GT2 + T11(1) was rather low, although it was sufficiently high in PBL cultures with D66 + T11(1) to generate a potent LAK activity. Yet, PBL stimulated with D66 + T11(1) released concomitantly a high amount of IL-4 which inhibited the development of the LAK activity, as demonstrated by unmasking this activity with an anti-IL4 antiserum and which did not inhibit the T CTL activity; this IL-4 secretion was not seen with GT2 + T11(1). Therefore, stimulation by these two typical CD2 mAb pairs induce a striking different pattern of IL synthesis.