bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-2 induces IL-6 production in human monocytes.
Authors: Musso T , Espinoza-Delgado I , Pulkki K , Gusella G L , Longo D L , Varesio L 
Published: December 2022

Abstract
IL-2 is a potent activator of effector and secretory activities of human monocytes. Since monocytes are an important source of IL-6, we investigated whether IL-2 can induce IL-6 production and whether regulatory circuits can modulate this process. We found that stimulation of monocytes with IL-2 induced expression of IL-6 mRNA and bioactivity in a dose-dependent manner. Production of IL-6 in monocytes can be induced by other cytokines such as IL-1 beta. By using mAb alpha-IL-1 beta we showed that IL-2-induced IL-6 production is not mediated by the autocrine stimulation of IL-1 beta elicited by IL-2. IL-6 induction by monocytes is not a common response to activating signals because IFN-gamma did not induce IL-6 expression under conditions in which it elicits tumoricidal activity. In contrast, IFN-gamma could completely abrogate the induction of IL-6 expression by IL-1 beta but did not affect the levels of mRNA and the secretion of IL-2-elicited IL-6. We have previously reported that transforming growth factor-beta inhibits IL-6 production in response to IL-1 beta. Studies on the inhibitory activity of transforming growth factor-beta demonstrated that this cytokine differs from IFN-gamma because it inhibited both IL-1- and IL-2-induced IL-6 expression. These data demonstrate that, in human monocytes, both IL-1 and IL-2 stimulate IL-6 expression by independent mechanisms that can be dissociated by the susceptibility to the inhibitory effect of IFN-gamma. IL-6 production is also down-regulated by TGF-beta, whose inhibitory activity is stimulus-unrelated.
Modulation of interferon consensus sequence binding protein mRNA in murine peritoneal macrophages. Induction by IFN-gamma and down-regulation by IFN-alpha, dexamethasone, and protein kinase inhibitors.
Authors: Politis A D , Sivo J , Driggers P H , Ozato K , Vogel S N 
Published: December 2022

Abstract
IFN play a central role in the activation of macrophages by inducing the expression of several proteins which, in turn, result in increased functional capabilities. Homologous interferon responsive sequences have been found in many IFN-inducible genes, and the gene for a protein that binds these sequences (interferon consensus sequence binding protein, ICSBP) has recently been cloned. In this study, the regulation of ICSBP mRNA induction by IFN-gamma was characterized in murine thioglycolate-elicited peritoneal macrophages. Northern blot analysis revealed two ICSBP mRNA species from these cells. Steady-state levels of both of these species were elevated by IFN-gamma at doses consistent with many IFN-gamma-induced macrophage functional responses. ICSBP mRNA levels increased within 1 h of IFN-gamma treatment, peaked between 4 and 6 h, and subsequently declined to approach baseline levels by approximately 24 h. IFN-alpha, at a concentration shown previously to modulate macrophage surface markers and functions, had no effect on ICSBP message levels alone, but antagonized the IFN-gamma-induction of ICSBP mRNA. IFN-gamma-induction of ICSBP mRNA is resistant to cycloheximide but sensitive to protein kinase inhibitors (H7, H8, HA-1004, staurosporine) at doses that suggest that protein kinase C is a likely target. ICSBP mRNA induction is also inhibited by dexamethasone, a synthetic glucocorticoid, well known as an anti-inflammatory drug capable of influencing gene expression in macrophages. The characterization of ICSBP mRNA regulation should help identify functions for this putative IFN trans-acting factor in macrophage activation.
Surface expression of functional IgE binding protein, an endogenous lectin, on mast cells and macrophages.
Authors: Frigeri L G , Liu F T 
Published: December 2022

Abstract
IgE-binding protein (epsilon BP) is a galactoside-specific lectin containing an S-type carbohydrate-recognition domain. It was originally identified in rat basophilic leukemia cells and is now known to be identical to a macrophage surface Ag, Mac-2, and lectins designated as CBP 35/L-34/RL-29. It has also been related to a nonintegrin laminin-binding protein isolated from mouse macrophages. In this report we have shown the following: epsilon BP is present in variable amounts in several mast cell lines, and the surface expression of epsilon BP in these cell lines is quite variable and does not correlate with the total amount of epsilon BP in the cell. epsilon BP is displayed on the cell surface in a manner that is reversible by lactose, most likely through attachment to yet unidentified glycoconjugates. The putative epsilon BP binding sites on the cell surface can be readily demonstrated by using radiolabeled epsilon BP, and the sites are present in comparable amounts in various cell lines. Expression of epsilon BP on the cell surface can be regulated; the most notable example is the upregulation of surface epsilon BP on RBL cells activated through the high-affinity IgE receptor by IgE immune complexes. Cell-surface epsilon BP is functional as measured by its ability to promote adhesion of trypsinized rabbit erythrocytes to mast cells and macrophages. On the basis of these results and reported properties of related lectins, we propose that the lectin represented by epsilon BP is a new class of cell-adhesion protein.
Release of newly synthesized platelet-activating factor (PAF) from human polymorphonuclear leukocytes under in vivo conditions. Contribution of PAF-releasing factor in serum.
Authors: Miwa M , Sugatani J , Ikemura T , Okamoto Y , Ino M , Saito K , Suzuki Y , Matsumoto M 
Published: December 2022

Abstract
The behavior of platelet-activating factor (PAF) produced in stimulated human polymorphonuclear leukocytes (PMN) was investigated in the presence of serum under conditions close to those existing in vivo. When the cells were stimulated in the presence of the serum obtained from a PAF acetylhydrolase (PAF-AH)-deficient Japanese subject, over 60% of synthesized PAF was detected in the extracellular medium by bioassay, scintillation proximity RIA and selected ion monitoring/gas chromatography/mass spectrography analysis. The release of PAF from PMN after stimulation with FMLP and A23187 was also observed in the presence of normal serum treated with acid to inactivate PAF-AH. The heterogeneity of the molecular species of extracellular PAF was similar to that of intracellular PAF produced in stimulated PMN in the presence of PAF-AH-deficient serum, ruling out the possibility that a specific molecular species of PAF was preferentially released from the cells in the presence of the serum. As these data suggested the occurrence of PAF-releasing factor(s) in the serum, an attempt was made to partially purify this factor from PAF-AH-deficient serum and acid-treated normal serum by ammonium sulfate fractionation and column chromatography with DEAE-Cellulofine and Sepharose CL-6B. The molecular mass of PAF-releasing factor revealed on a TSK gel G3000 SW HPLC column was 240 kDa, which was different from that of albumin. The binding assay, newly developed for this study, revealed that the PAF-binding activity of PAF-releasing factor is stronger than that of albumin, and that the PAF-releasing factor forms a complex with PAF at low concentration (10(-9) M). PAF bound to this factor was difficult to be hydrolyzed by serum PAF-AH. On the other hand, the PAF/PAF-releasing factor complex had aggregatory activity toward washed rabbit platelets. These observations suggest that certain protein(s) releases and carries the PAF newly synthesized by PMN in blood plasma/serum. Thus it appears that PAF functions as an autacoid in vivo, along with other mediators.
Induction of C3 expression in astrocytes is regulated by cytokines and Newcastle disease virus.
Authors: Rus H G , Kim L M , Niculescu F I , Shin M L 
Published: December 2022

Abstract
Synthesis of complement proteins and their regulation in resident cells of the central nervous system are important pathophysiologic factors that can affect the outcome of inflammatory central nervous system diseases. Primary cultures of rat astrocytes constitutively express C3 mRNA and produce C3 protein; both of them were enhanced by LPS or by a live as well as inactivated Newcastle disease virus, a neurotropic paramixovirus. TNF, IL-1 beta, and IL-8 also increased the levels of C3 mRNA and protein whereas IL-1 alpha and IL-6 had no effect, although all of these cytokines are inducible by LPS. LPS stimulation in the presence of cycloheximide decreased the LPS-mediated C3 mRNA induction by 60%. These data suggest that LPS effect on C3 regulation is mediated directly by LPS as well as by LPS-induced cytokines. Interestingly, C3 mRNA induced by Newcastle disease virus or inactivated Newcastle disease virus was inhibited by protein kinase inhibitors, H-7 and staurosporine, whereas these inhibitors had no effect on C3 induction mediated by LPS or cytokines, indicating the existence of different signal transduction pathways.
Exon encoding the antigen-binding site of MHC class II beta-chains is divided into two subregions with different evolutionary histories.
Authors: Sigurdardóttir S , Borsch C , Gustafsson K , Andersson L 
Published: December 2022

Abstract
The evolution of the Ag-binding site of polymorphic class II molecules was investigated by comparing the pattern of silent and replacement substitutions in the first domain exon of DQB and DRB alleles in two distantly related mammalian species, man and cattle. We show that the first domain can be subdivided into two regions, corresponding to the beta-strand and alpha-helical regions, with distinct evolutionary histories. The data for the alpha-helical region are in conflict with the standard phylogeny of mammalian class II genes. In this region, there is only weak locus divergence at the protein level and the frequency of silent substitutions is extremely low between nonorthologous genes (i.e., DQB-DRB) within species. We propose that the major underlying cause for the observed sequence similarity in the alpha-helical region is due to a selective constraint restricting the sequence divergence at the protein level. This selective constraint may be related to the interaction between different isotypic forms of polymorphic class II beta-chains and a common ligand. The extremely low frequencies of silent substitutions between nonorthologous genes within species are most likely due to the transfer of sequence information between loci by the occurrence of gene conversion-like events in the particular gene segment.
Immune response to Moloney murine leukemia virus nonviral, tumor-associated antigens fails to provide in vivo tumor protection.
Authors: Jiang D , Flyer D C 
Published: December 2022

Abstract
Two distinct populations of CTL have previously been shown to be generated in lymphocyte cultures derived from the spleens of C57BL/6 mice that have rejected Moloney murine leukemia virus:Moloney sarcoma virus (MoMuLV:MSV)-induced tumors. One population is specific for MoMuLV viral Ag whereas the other appears to be directed against a nonviral, tumor-associated Ag (TAA). Using a virus-negative variant of the MoMuLV-induced lymphoma MBL-2 that has retained the expression of the MuLV:TAA, we attempted to further characterize the MuLV:TAA-specific CTL population. First, this same pattern of CTL reactivity was observed using a variety of immunization protocols indicating that the TAA-specific CTL population was not an artifact of the original immunization protocol but was a reproducible component of the MoMuLV CTL response. Moreover, CTL precursor frequency analysis indicates that the MuLV:TAA-specific CTL represent approximately 60% of the CTL detected in in vitro cytotoxicity assays. However, when the role of MuLV:TAA CTL in the in vivo rejection of MoMuLV-induced tumors was examined, no role for the MuLV:TAA-specific CTL response could be determined. Immunization protocols that had been shown to give rise to both CTL populations were capable of protecting mice from tumor development after a challenge with the parental MBL-2 tumor cell line but not the virus-negative variant MBLv cell line. In addition, immunization with the variant, shown to give rise to only MuLV:TAA-specific CTL capable of lysing both MBL-2 and MBLv in vitro, failed to protect mice from a tumor challenge of either cell type.
Human postnatal thymocytes generate phenotypically immature CD3dim, CD5dim, CD1abright progeny in organ culture.
Authors: Merkenschlager M , Fisher A G 
Published: December 2022

Abstract
We previously described an organ culture system that supports the in vitro development of human fetal thymocytes in murine alymphoid thymic rudiments without addition of exogenous factors. This approach to study human T cell precursors is limited by the requirement for fetal tissue. We show that human thymocytes from pediatric sources can be expanded under similar conditions. Organ cultures generated predominantly CD4 CD8 double positive cells, most of which maintained the phenotype CD3dim, CD5dim, and CD1abright, characteristic for double positive thymocytes ex vivo. This culture system should facilitate in vitro studies on human thymocyte development and repertoire selection.
A toxic shock syndrome toxin-1 peptide that shows homology to mycobacterial heat shock protein 18 is presented as conventional antigen to T cells by multiple HLA-DR alleles.
Authors: Ramesh N , Spertini F , Scholl P , Geha R 
Published: December 2022

Abstract
We observe that PBMC from most adults (16 of 18 subjects tested) show a small but significant in vitro proliferative response to a 30-amino acid-long peptide (peptide 2, amino acids 34-63) derived from toxic shock syndrome toxin. By contrast, PBMC from newborn blood and thymocytes do not proliferate to this peptide, and furthermore, peptide 2 did not displace the binding of radiolabeled TSST-1 to MHC class II positive cells, nor did it induce IL-1 beta mRNA in monocytes, indicating that this peptide does not behave as a superantigen. Proliferation of PBMC to peptide 2 could be blocked by anti-HLA-DR, but not by anti-HLA-DP or DQ mAb, suggesting that HLA-DR molecules are the restriction elements for the recognition of this peptide by T cells. This premise was further confirmed by demonstrating that mouse L cells transfected with human HLA-DR, but not HLA-DP or DQ molecules, supported the proliferation of purified T cells to peptide 2. Studies with subjects of known HLA-DR types showed that all types tested are capable of responding to this peptide, PBMC from adults exposed to mycobacterial Ag showed significantly better proliferative response to peptide 2 than unexposed adults. Studies with truncations of this peptide suggest that a "core" region of eight amino acids that is conserved between low m.w. heat shock proteins and peptide 2 may be critical to T cell recognition of this peptide. The universal presentation of peptide 2 by HLA-DR molecules may contribute to the widespread natural immunity observed against toxic shock syndrome toxin.
A common precursor for CD4+ T cells producing IL-2 or IL-4.
Authors: Röcken M , Saurat J H , Hauser C 
Published: December 2022

Abstract
To investigate whether CD4+ T cells are predetermined to produce a given pattern of lymphokines, we have used a culture system that allows the controlled induction of either IL-2- or IL-4-producing CD4+ T cells. Single, freshly isolated murine CD4+ T cells were activated with Con A, rIL-2, and APC; the developing clones were split and then cultured for an additional 14 days with either rIL-2 alone or with rIL-2 and anti-CD3 stimulation. Subclones expanded in the presence of rIL-2 alone produced predominantly IL-2, although subclones derived from the same precursor and expanded in the presence of rIL-2 and a mitogenic antibody to CD3 released predominantly IL-4. Subclones expanded for 2 wk in the presence of rIL-2 plus a mitogenic mAb to CD3 released up to 60 times more IL-4 but only 1/90 the amount of IL-2 released by subclones derived from the same precursor cell and expanded with rIL-2. Both phenotypes can be derived from IL-2-producing precursor cells. These results demonstrate that IL-2-producing clones can be derived from the same cells as IL-4-producing clones and are most consistent with the view that the IL-2-producing Th1 or the IL-4-producing Th2 phenotype of a T cell clone is acquired during T cell differentiation and is not secondary to the expansion of distinct subpopulations that are predetermined to produce a specific cytokine pattern.
Purified HLA class II peptide complexes can induce adherence and activation of peptide-specific human T cell clones.
Authors: van Schooten W C , Maiore T , Jones K R , Paborsky L 
Published: December 2022

Abstract
An initial event in T cell activation is the specific adherence of T cells via their T cell receptor to the MHC peptide complex. We have studied this adherence by incubating T cells with preformed HLA DR4Dw4 peptide complexes attached to a solid support. Adherence of sodium 51Cr-labeled T cell clones specific for the influenza hemagglutinin peptide, HA 307-319, was maximal after 15 min and was specific for the HLA DR4Dw4-HA 307-319 complex. The binding was temperature dependent and could be blocked with azide or protein kinase C inhibitors, indicating that for adherence the T cells need to be metabolically active and have a functioning protein kinase C pathway. The adherence could be blocked with CD4- or CD3-reactive murine mAb, suggesting that the TCR and CD4 molecules work in concert to induce strong adherence to the HLA DR4Dw4-HA 307-319 complex. A subsequent event in T cell activation is proliferation, which is thought to need additional proteins such as IL-1 or other adhesion molecules. MHC peptide complexes coated on microtiter plates also induced proliferation in the human T cell clones. Removal of any monocytes by treatment of human T cell clones with anti-CD14 in conjunction with C, followed by purification over a nylon wool column, did not abrogate proliferation. After prolonged culture of the T cell clones in plates coated with peptide-pulsed HLA DR4Dw4 in the presence of IL-2, the T cell clones continued to proliferate in response to peptide. These results suggest that human T cell clones do not require a second signal from a monocyte or other APC to proliferate.
Cyclosporin A and FK506 mediate differential effects on T cell activation in vivo.
Authors: Bishop D K , Li W 
Published: December 2022

Abstract
Modified limiting dilution analysis techniques were used to evaluate the effects of the immunosuppressants cyclosporin A (CsA) and FK506 on alloantigen-induced T cell activation in vivo. Treatment of sponge matrix allograft recipients with either CsA or FK506 inhibited lymphocytic infiltration of the allograft, a process thought to be dependent on local lymphokine production. In addition, both immunosuppressants markedly reduced the absolute number of lymphocytes recovered from the draining lymph nodes (LN) and prevented CTL activation in the LN. However, Ag-primed helper T lymphocytes (HTL) were present in the draining LN of sponge allograft recipients treated with CsA, but not in recipients treated with FK506. T cell depletion experiments were performed to determine the phenotype of primed HTL in the LN of untreated and CsA-treated sponge allograft recipients. In untreated sponge allograft recipients, CD4+ and CD8+ Ag-primed HTL were present in the draining LN in equivalent numbers. In contrast, the majority of primed HTL in the LN of CsA-treated sponge allograft recipients were CD8+, rather than CD4+ T cells. These observations indicate that CsA and FK506 exert distinct in vivo effects at the level of HTL priming, and CD4+ and CD8+ HTL exhibit differential sensitivity to CsA in vivo.
Allogeneic chimerism in scid mice after neonatal transfer of bone marrow.
Authors: Cowing C , Gilmore G L 
Published: December 2022

Abstract
Allogeneic chimeras are valuable tools for studies of complex immune cell interactions in vivo. Mice with severe combined immune deficiency (scid) should be ideal hosts for chimerism with allogeneic bone marrow cells as these animals lack mature T and B lymphocytes capable of reacting against donor alloantigens. However, it has been difficult to achieve full reconstitution of adult scid mice even using coisogenic bone marrow grafts without prior irradiation of the recipient. We explored ways to generate complete reconstitution of scid mice with allogeneic bone marrow. Unirradiated adult scid recipients of allogeneic bone marrow were only marginally reconstituted. Adult scid mice pretreated with 250 R were reconstituted with allogeneic bone marrow as measured by serum IgM concentration, peripheral lymphoid cellularity, and mitogen responses, but a potentially important immunologic deficit was found in these mice: 250 R caused a 70% loss of scid macrophages and dendritic cells which persisted at least 5 months. By contrast, when scid mice were injected i.p. with allogeneic bone marrow within the first 24 h after birth, rapid and complete reconstitution of both T and B cell lineages was achieved, and the animals had APC that were both donor and host in origin. Considering the extent and duration of engraftment (43 wk) by allogeneic cells in neonatally transplanted scid mice, it was anticipated that their bone marrow would be chimeric. However, the bone marrow contained very few donor-derived cells, suggesting that lymphopoiesis may be taking place in other organs in these chimeras.
Stimulation of human monocytes via CD45, CD44, and LFA-3 triggers macrophage-colony-stimulating factor production. Synergism with lipopolysaccharide and IL-1 beta.
Authors: Gruber M F , Webb D S , Gerrard T L 
Published: December 2022

Abstract
Stimulation of human monocytes with immobilized mAb directed against the CD45, CD44, or LFA-3 Ag induced the production of macrophage-CSF (M-CSF). M-CSF-specific transcripts appeared at 3 h poststimulation, were further increased by 12 h, and were still detectable at 24 h. M-CSF gene expression was accompanied by the induction of small but detectable amounts of M-CSF protein. LPS and IL-1 beta, but not IL-6 or TNF-alpha, dramatically augmented the ability of anti-CD45, anti-CD44, and anti-LFA-3 antibodies to induce M-CSF secretion but failed to stimulate M-CSF secretion in the absence of antibody. M-CSF activity in the culture supernatants was first detectable at 8 h of culture, peaked at day 2, and declined thereafter. Purified F(ab)2 fragments of anti-CD45 antibody were also effective in inducing M-CSF message and secretion, indicating that the Fc gamma RII is not involved in this response. Stimulation of cells with antibodies to the monocyte surface Ag MAC-1, LFA-1, and ICAM-1 did not result in M-CSF secretion. Moreover, LPS and IL-1 beta failed to synergize with these Ag in inducing M-CSF production. Together, these results indicate that stimulation of monocytes via the cell surface Ag CD45, CD44, and LFA-3 can trigger M-CSF production. However, second signals that can be provided by IL-1 beta or LPS are required to regulate optimal M-CSF protein secretion.