bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell specificity for class II (I-A) and the encephalitogenic N-terminal epitope of the autoantigen myelin basic protein.
Authors: Zamvil S S , Mitchell D J , Moore A C , Schwarz A J , Stiefel W , Nelson P A , Rothbard J B , Steinman L 
Published: December 2022

Abstract
The role of class II restriction in T cell recognition of an epitope of the autoantigen myelin basic protein (MBP) has been investigated. Encephalitogenic PL/J(H-2u) and (PL/J X SJL/J(H-2s))F1 ((PLSJ)F1) clones, isolated after immunization with intact MBP, recognize the N-terminal 11 amino acid residues of MBP in association with I-Au class II molecules. The synthetic peptide MBP 1-11 has been tested in vivo for induction of EAE. Clinical and histological EAE occurs in PL/J and (PLSJ)F1 mice but not SJL/J. The class II restriction of T cells primed with MBP 1-11 has been examined in primary cultures in vitro. Similar to encephalitogenic T cell clones, isolated after continuous selection in vitro, the population of MBP 1-11-specific proliferative PL/J and (PLSJ)F1 T cells, recognize this epitope in association with I-Au class II molecules. Not all MBP-specific T cell clones which are restricted to I-Au class II molecules cause autoimmune encephalomyelitis. The specificity of these non-encephalitogenic clones has been examined in this report. These clones also recognize MBP 1-11. Thus recognition of an encephalitogenic T cell epitope is not sufficient for induction of EAE.
Granulocyte-macrophage colony-stimulating factor augments the primary antibody response by enhancing the function of antigen-presenting cells.
Authors: Morrissey P J , Bressler L , Park L S , Alpert A , Gillis S 
Published: December 2022

Abstract
Purified, recombinant-derived murine granulocyte-monocyte colony-stimulating factor was found to enhance the primary in vitro immune response to SRBC by murine spleen cells. In determining the mechanism of this augmentation, it was found that only splenic adherent cells and neither resting nor activated T cells nor B cells expressed specific receptors for GM-CSF. When splenic adherent cells were pulsed briefly with GM-CSF before addition to macrophage-depleted cultures, they reconstituted the PFC response to a significantly greater degree than did control macrophages. Splenic adherent cells incubated overnight with SRBC plus GM-CSF were also more efficient antigen-presenting cells than splenic adherent cells incubated with antigen alone. The mechanism of this enhanced antigen presentation was found to be due to a GM-CSF-dependent increase in the level of IL 1 secretion and Ia antigen expression. Consistent with these data was the finding that GM-CSF augmented IL 2 production by splenic T cells in response to suboptimal concentrations of Con A. Finally, the day 5 in vivo antibody response (as measured by serum titers) of mice immunized with a low dose of SRBC was enhanced by two daily inoculations of GM-CSF. Thus, the role that GM-CSF plays in augmenting immune responses may not be solely accounted for by its ability to cause the proliferation or differentiation of macrophages, but more than likely includes its ability to enhance the function of antigen-presenting macrophages.
Interleukin 1 release by human monocytes treated with liposome-encapsulated lipopolysaccharide.
Authors: Bakouche O , Koff W C , Brown D C , Lachman L B 
Published: December 2022

Abstract
Liposome therapy offers a unique method of delivering antifungals, antiprotozoans, and macrophage-activating factors directly to reticuloendothelial cells. Although liposomes are entering clinical trials, their effect on Il 1 synthesis and release has yet to be determined. The beneficial, as well as possible pathological, effects of liposome therapy may be due to IL 1 released by reticuloendothelial cells. This study examined the effects of multilamellar phospholipid vesicles on the synthesis and release of IL 1 from human peripheral blood monocytes. Liposomes consisting of phosphatidylcholine and phosphatidylserine in molar ratio of 7:3 did not stimulate IL 1 release, and did not diminish the level of IL 1 release when monocytes were subsequently stimulated with LPS or Staphylococcus aureus. Surprisingly, LPS encapsulated in liposomes failed to stimulate IL 1 release from monocytes. This defect was limited to the release of IL 1, because monocytes stimulated with liposomes containing LPS had control levels of intracellular (cytosolic) and membrane IL 1. By contrast, LPS associated with lyophilized liposomes induced the secretion of IL 1 and behaved similarly to free LPS. These findings indicate that LPS activation of monocytes may involve not only the synthesis of IL 1 but activation of the secretory mechanism for IL 1, and that these two events could be independent, that the density of LPS molecules at the surface of the liposome may influence the degree of monocyte activation as measured by intracellular IL 1 synthesis, membrane accumulation, and secretion into the medium, and that intracellular lipids may not interfere with the secretory mechanism, because liposomes made with phospholipids differing in acyl chain length or the headgroup behaved identically.
Down regulation of the receptors for tumor necrosis factor by interleukin 1 and 4 beta-phorbol-12-myristate-13-acetate.
Authors: Holtmann H , Wallach D 
Published: December 2022

Abstract
Binding of radiolabeled tumor necrosis factor (TNF) to cell surface receptors was markedly reduced in human foreskin fibroblasts and cells from SV-80 and HeLa cell lines subsequent to treatment with interleukin 1 (IL-1) or 4 beta-phorbol-12-myristate-13-acetate (PMA). The decrease in TNF binding was initiated within minutes of application of IL-1 or PMA and could not be blocked by cycloheximide, suggesting that it is independent of protein synthesis. Scatchard plot analysis of TNF binding to the SV-80 cells indicated that its decrease in response to IL-1 and PMA reflects a reduced amount of TNF receptors, with no change in their affinity. IL-1 and PMA together had an additive effect on TNF binding. Treatment with TNF did not result in decreased binding of IL-1 to its receptors nor did TNF and IL-1 compete directly for their respective receptors. Human U937 cells on which receptors for IL-1 were below detectable levels exhibited no decrease in TNF binding when treated with IL-1, but did so in response to PMA. In addition to a decrease in TNF receptors, cells treated with IL-1 or PMA exhibited a lesser vulnerability to the cytolytic effect of TNF. The two kinds of changes were not completely correlated. A particularly notable dissimilarity was evident when comparing the rate of their reversal: the TNF receptor level was fully recovered within a few hours of removal of IL-1 or of the water-soluble analogue of PMA, 4 beta-phorbol-12,13-dibutyrate, from pretreated SV-80 cells; yet at that time resistance to the cytotoxicity of TNF was still prominent. These findings indicate that IL-1 as well as tumor-promoting phorbol diesters can down regulate cellular response to TNF by inducing a decrease in the number of receptors for TNF, and apparently through some other effect(s) as well.
The murine lymphocyte receptor for IgE. V. Biosynthesis, transport, and maturation of the B cell Fc epsilon receptor.
Authors: Keegan A D , Conrad D H 
Published: December 2022

Abstract
The post-translational processing and maturation of the receptor for IgE (Fc epsilon R) on murine hybridoma B cells were studied to determine the carbohydrate content and the importance of processing events in cell surface expression and ligand (IgE) binding ability. Endo and exoglycosidase treatment demonstrated that the mature receptor is composed of two to three complex-type N-linked oligosaccharides and contains sialic acid. Pulse-chase experiments indicated that the receptor is synthesized as a 44,000 dalton precursor that begins to be processed by 1 hr to the mature 49,000 dalton form, and the latter is expressed at the cell surface by 2 hr. It was determined that the processing included the conversion of N-linked oligosaccharides to the complex type as well as an additional processing event, because in the presence of tunicamycin, the receptor is synthesized as a 36,000 dalton precursor that is processed to a 38,000 dalton species. Analysis of the effects of tunicamycin treatment and endo F digestion on soluble Fc epsilon R isolated from cell supernatants demonstrated the existence of several m.w. species of Fc epsilon R fragments, and indicated that only the higher m.w. fragments were N-glycosylated. The use of several inhibitors of the N-linked carbohydrate processing pathway demonstrated that the addition of core N-linked side-chains, but not their processing to the complex type, is required for cell surface expression of Fc epsilon R. Also, processing of N-linked carbohydrate is not required for ligand binding activity. Finally, IgE affinity chromatography indicated that the 49,000 and 38,000 dalton (tunicamycin) Fc epsilon R bind IgE more effectively than their precursor forms, 44,000 and 36,000 daltons, respectively, indicating that a processing event independent of N-linked glycosylation is necessary for optimal ligand binding activity.
Species-specific antibodies to Leishmania tropica (minor) recognize somatic antigens and exometabolites.
Authors: Jaffe C L , Sarfstein R 
Published: December 2022

Abstract
Monoclonal antibodies were raised against membranes of Leishmania tropica (formerly L. tropica minor). These antibodies do not react with membranes or homogenates prepared from any other species of Leishmania examined. The antigens identified by all four monoclonal antibodies reside on the external surface of the promastigote and are released into the culture medium. Immunoprecipitation of metabolically ([3H]glucose, -glucosamine, or [35S]methionine)-labeled, [125I]lactoperoxidase-labeled, or Western blot analysis of the parasites identified species-specific determinants residing on several different molecules with Mr between 12,000 and 140,000. All of the monoclonal antibodies appear to recognize determinants on a common [3H]sugar-labeled glycoconjugate, Mr = 32,000 to 44,000, but also react with additional components of 55,000, 80,000, 92,000, and 130,000 m.w. Antibody binding to the parasites is very sensitive to mild oxidation with periodate, suggesting that the species-specific determinants are carbohydrate in nature.
Maleylated bovine serum albumin triggers cytolytic function in selected populations of primed murine macrophages.
Authors: Somers S D , Hamilton T A , Adams D O 
Published: December 2022

Abstract
The complex algal polysaccharide fucoidan has been reported as serving as a second signal for activation of macrophages primed in vivo by BCG. To assess the potential utility of this observation in analyzing biochemical mechanisms involved in macrophage activation, we examined the triggering effects of maleylated bovine serum albumin (maleylated-BSA), a defined molecule that clears via similar mechanisms. Cytolysis of P815 mastocytoma targets was triggered by maleylated-BSA, in a dose-dependent manner, in murine peritoneal macrophages primed in vivo by BCG. Unlike bacterial LPS, which triggered cytolysis when used to pretreat the macrophages, maleylated-BSA was only effective if present throughout the period of macrophage-target cytolytic interaction. Maleylated-BSA alone did not lyse the P815 targets and did not affect the binding of such targets by macrophages. Maleylated-BSA was equally effective in triggering cytolysis in BCG-primed macrophages from C3H/HeJ or C3H/HeN mice. Macrophages primed in vitro with IFN-gamma, however, could not be triggered by maleylated-BSA, even though these macrophages bound maleylated-BSA comparably to the BCG-primed macrophages. When responsive macrophages were fully activated in vitro by IFN-gamma and LPS and then allowed to decay to the primed state, maleylated-BSA was then as effective as LPS in triggering cytolysis. Taken together, the results indicate that maleylated-BSA can trigger cytolysis in certain populations of primed macrophages but not in others.
Bi-specific monoclonal antibodies: selective binding and complement fixation to cells that express two different surface antigens.
Authors: Wong J T , Colvin R B 
Published: December 2022

Abstract
A new dimension of immunotherapeutic selectivity might be achieved if antibodies could distinguish cells that co-express two different surface antigens. Bi-specific monoclonal antibodies (BSMAB) with two different antigen combining sites that share a common Fc region theoretically might have such a potential. Two such BSMAB were produced by hybrid-hybridoma clones prepared by fusion of pre-existing hybridomas and were purified by isoelectric focusing. CD3,4 (IgG2a, IgG2b) recognizes the T cell surface antigens CD3 and CD4, and CD3,8 (IgG2a, IgG2a) recognizes CD3 and CD8. These BSMAB promote complement-mediated lysis of target cells that bear both surface antigens 25 to 3125 times more efficiently than those that express only one of the antigens. This selectivity results from the increased avidity of these antibodies for cells with both antigens, as reflected by the increased surface immunoglobulin concentration detected by flow cytometry. It was also demonstrated that there exists a threshold surface immunoglobulin density necessary for antibody-dependent complement-mediated cytotoxicity microtiter assays for the various IgG antibodies tested in both bivalent and monovalent binding. These results support the associative model of IgG-mediated complement fixation.
Interleukin 2 mediates an alteration in the T200 antigen expressed on activated B lymphocytes.
Authors: Cook R G , Landolfi N F , Mehta V , Leone J , Hoyland D 
Published: December 2022

Abstract
We have examined the effect of exogenous IL 2 on cell surface antigen expression in LPS/dextran sulfate-activated murine B cells with the use of a panel of fluorescein-conjugated lectins. Elevated binding of the lectins PNA and SBA to activated B cells was found to be mediated by IL 2-containing supernatants from stimulated EL4 cells as well as by recombinant IL 2. These lectins have specificity for terminal beta-(1-3)-N-acetylgalactosaminyl residues; thus, the quantity or accessibility of these moieties is mediated by IL 2 in activated B lymphocytes. PNA binding in all strains tested, regardless of MHC or background genes, was found to be elevated fivefold to 15-fold by exogenous IL 2. To observe this effect, IL 2 must be added during the first 24 hr of culture. Based on anti-Thy-1 + complement depletion studies, T cells were not required, suggesting a direct effect of IL 2 on B cells. The glycoprotein responsible for this elevated binding of PNA has an Mr of approximately 220K and by immunodepletion was shown to belong to the T200 (Ly-5) family of cell surface antigens. These data demonstrate that exogenous IL 2 can mediate alterations in T200 expression on activated B cells that may be related to IL 2-driven modulation of B cell proliferation and/or differentiation.
T cell growth without serum.
Authors: Herzberg V L , Smith K A 
Published: December 2022

Abstract
Most in vitro T cell proliferation experiments are performed by using serum-supplemented medium, yet the actual contributions of serum components to cell cycle progression remain ill-defined, thus complicating attempts to fully define requirements for cell division. By utilizing a functional separation between T cell receptor-triggered "competence" and IL 2-promoted "progression" to independently assess serum requirements during each cell cycle stage, it was shown that serum serves an essential, active role only during the early events of the competence phase (G0-G1 transition) of T cell activation. Serum is required for optimal IL 2 production and the cell surface expression of IL 2 receptors after the stimulation of the T3/Ti antigen receptor complex. In contrast, serum does not function actively during IL 2-mediated progression through the G1 phase of the cycle. Serum proteins serve only a passive role at this stage, preventing the adsorption of IL 2. This same effect can be provided by any number of proteins including IL 2 itself, or even a high cell concentration. Supplementation of serum-free T cell cultures solely with IL 2 and transferrin is sufficient for maximal T cell proliferation, although the time of the peak response is delayed owing to a suboptimal rate of IL 2 receptor expression. Accordingly, the realization that serum is only necessary for the earliest stage of T cell activation will now enable studies designed to identify the critical individual serum components and to define their mechanism of action.
Selective elimination of non-lpr lymphoid cells in mice undergoing lpr-mediated graft-vs-host disease.
Authors: Perkins D L , Michaelson J , Glaser R M , Marshak-Rothstein A 
Published: December 2022

Abstract
The transfer of lpr BM stem cells into lethally irradiated non-lpr recipients (including the congenic MRL/+ differing only at the lpr locus) causes GVHD characterized by a wasting syndrome. In this study we investigated the interaction between the autoimmune (lpr) and normal (A-Thy) B, T, and RBC cell lineages in two types of radiation chimeras: MRL/lpr plus A-Thy----(MRL/lpr X A-Thy)F1 and MRL/+ plus A-Thy----(MRL/lpr X A-Thy)F1. Analysis of B cell repopulation by competitive RIA of serum Igh-1 allotype showed that both the MRL and the A-Thy donor cells initially engrafted. However, by 2 to 4 mo post-transplantation the normal A-Thy allotype was barely detectable (reduced greater than 2 orders of magnitude), whereas the autoimmune MRL/lpr allotype persisted at normal levels. Similarly, investigation of the donor origin of peripheral blood T cells by two-color flow cytometry showed that by 8 mo post-transplantation normal A-Thy T cells had been eliminated and only MRL/lpr T cells were present in the circulation. In contrast, erythrocytes from both the MRL/lpr and A-Thy donor strains successfully engrafted the F1 recipients and persisted until the termination of the study. Control chimeras transplanted with a mixture of MRL/+ plus A-Thy BM were stably engrafted with both donor strains in both the erythroid and lymphoid populations. Additional experiments in which either B6/lpr or MRL/lpr (and B6/+ or MRL/+ control) BM cells were transferred into (MRL/lpr X B6/+)F1 and (MRL/lpr X B6/lpr)F1 recipients demonstrated that the development of GVHD was not simply due to increased alloreactivity by the lpr donor cells. In these chimeras only the recipients heterozygous (but not homozygous) for the lpr gene developed lpr-GVHD, although both types of recipients had identical genotypes except at the lpr locus.
Mechanism of cell contact-mediated inhibition of natural killer activity.
Authors: Heiskala M K , Carpén O , Saksela E , Timonen T 
Published: December 2022

Abstract
Natural killer cell activity is inhibited by primary cultures of monolayer cells. In this study, we analyzed the mechanism of the inhibition. Inhibited NK cells showed unaltered binding capacity to NK sensitive K562 cells. The orientation of the effector cells' actin-containing microfilaments, an event known to occur during the programming for the lysis stage in lytic conjugates, was unaffected by the inhibition. In single cell cytotoxicity experiments, the number of killer cells among conjugate-forming cells was reduced. The capacity of the inactivated NK cells to secrete cytotoxic factors upon stimulation with Con A was also impaired. Both NK-resistant inactivating target cells and NK-sensitive K562 cells were sensitive to the toxic factors secreted by NK cells. Thus, the results indicate that the target cell-mediated inactivation of NK cell is based on a block in the lethal hit stage, possibly due to reduced release of toxic factor(s) from the effector cells. The capacity of inactivated effector cells to mediate antibody-dependent cellular cytotoxicity was unimpaired, suggesting that the contact-mediated inhibition of cytotoxicity selectively affects NK cells.
Concomitant immunoglobulin E and immunoglobulin G1 formation in Nippostrongylus brasiliensis-infected mice.
Authors: Lebrun P , Spiegelberg H L 
Published: December 2022

Abstract
The immunoglobulin (Ig)E, IgG subclass, and IgM formation in vivo and in vitro were measured by radioimmunoassays in normal and immunodeficient mice infected with the parasite Nippostrongylus brasiliensis (Nbr). High IgE responder mice had higher IgE serum levels than low responder mice both before (100 to 250 vs 2 to 20 ng of IgE/ml) and after (17,000 to 27,000 vs 1,000 to 5,000 ng of IgE/ml) infection. In vitro, mesenteric lymph node cells formed 5- to 10-fold more IgE than the spleen cells. Nu/nu mice had less than 1 ng before and 5 ng of IgE/ml serum after Nbr infection; no IgE was detectable in cell supernatants. There was no difference in the in vivo and in vitro IgE formation between C57BL/6 and C57BL/6-beige mice. Both in vivo and in vitro Nbr-infected Xid+ mice (CBA/N; (CBA/N X BALB/c) F1 male) formed approximately twice the amount of IgE than Xid- mice. Concomitant with the rise of the IgE serum levels, the IgG1 serum level increased by 100 to 1,500 micrograms/ml over preinfection levels in all strains except nu/nu+ mice. The IgM serum level increased by 100 to 500 micrograms/ml. In contrast, the IgG2a and IgG2b levels decreased in most strains, and the IgG3 levels remained unchanged. Nu/nu+ mice showed an increase of all IgG subclasses after Nbr infection. The antibodies to an Nbr extract were predominantly of IgM and IgG1, except in SJL mice which also had IgG2b and nude mice which only had IgM antibodies. The concomitant increase of IgE and IgG1 formation in all but the nude strains suggests that the regulation of these two Ig isotypes may be linked via regulatory T helper cells, which corroborates recent data on the simultaneous induction of IgG1 and IgE synthesis in vitro by the B cell stimulatory factor 1.