bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age restriction in antigen-specific immunosuppression.
Authors: Doria G , Mancini C , Frasca D , Adorini L 
Published: January 2023

Abstract
Age-related alterations of antigen-specific T cell-mediated suppression have been examined in the 4-hydroxy-3-nitrophenyl acetyl (NP) system. Inducer suppressor T cells (Tsi) were activated in mice at the age of 3 mo (young) or 18 mo (old) by i.v. injection of NP-conjugated syngeneic spleen cells (SC). Spleen cells from the NP-SC-injected mice were subcultured in vitro with spleen cells from normal young or old mice to generate transducer suppressor T cells (Tst). Four days later subcultured cells were added to responder cell cultures 1 day before the PFC assays to trigger effector suppressor T cells (Tse). Responder cell cultures, containing NP-conjugated horse red blood cells (HRBC) and spleen cells from HRBC-primed young or old mice, were assayed on day 4 for anti-NP and anti-HRBC PFC. Suppression was found to be antigen specific and age restricted. NP-specific suppressor cells are easily induced in subculture if the Tsi and Tst cell populations are both derived from young or old mice. Conversely, if Tsi cells from young or old mice are subcultured with Tst cells from mice of a different age, suppression of the anti-NP PFC response is hardly observed. Age restriction was also found to operate in the interactions between subcultured and responder cell populations, indicating that age-matching is required for effective triggering of Tse cells by Tst cells. These results altogether suggest that aging may affect the recognition repertoire expressed in suppressor T cell subsets. Moreover, the finding that suppression is less efficient when exerted on responder spleen cells from old than from young mice provides an explanation for the increased frequency of autoimmune disorders in aging.
Direct activation of human resting T cells by IL 2: the role of an IL 2 receptor distinct from the Tac protein.
Authors: Bich-Thuy L T , Dukovich M , Peffer N J , Fauci A S , Kehrl J H , Greene W C 
Published: January 2023

Abstract
High concentrations of interleukin 2 (IL 2) were shown to produce a delayed but pronounced proliferation of purified resting T cells in the apparent absence of other activation signals. Because these stimulatory effects of IL 2 occurred in the absence of detectable Tac+ cells, the possibility that IL 2 might be initially interacting with an IL 2 binding protein distinct from the Tac protein was studied. Chemical cross-linking studies with 125I-IL 2 revealed the presence of an IL 2 binding protein distinct from the Tac protein on the surface of these unstimulated T cells. This second IL 2 receptor has an estimated molecular size of 70,000 daltons, lacks reactivity with the anti-Tac antibody, and appears to be identical to the p70 protein recently proposed as a component of the high affinity IL 2 receptor. Scatchard analysis of IL 2 binding assays performed with the unactivated T cells revealed approximately 600 to 700 p70 sites per cell and an apparent Kd of 340 pM. These data indicate that the p70 protein present on resting T cells binds IL 2 with an intermediate affinity compared with the previously recognized high and low affinity forms of the receptor and may account for the high concentration of IL 2 needed to induce resting T cell proliferation. To investigate the early biologic consequences of IL 2 binding to the p70 protein, potential changes in the expression of genes involved in T cell activation were examined. Northern blotting revealed the rapid induction of c-myc, c-myb, and Tac mRNA after stimulation of resting T cells with a high concentration of IL 2. The anti-Tac antibody did not inhibit IL 2 induced expression of these genes, suggesting that the p70 protein rather than the Tac antigen or the high affinity IL 2 receptor complex mediated this signal. However, in contrast to these early activation events, the anti-Tac antibody significantly inhibited IL 2 induced T cell proliferation. This finding implicates the high affinity form of the IL 2 receptor in the proliferative response of the IL 2 activated T cells. Thus these data support a two step model for the induction of resting T cell proliferation by high doses of IL 2 involving the initial generation of an activation or "competence" signal through the p70 protein and a subsequent proliferation or "progression" signal through the high affinity form of the receptor.
Activation of T lymphocytes through the Ly-6 pathway is defective in A strain mice.
Authors: Malek T R , Shevach E M , Danis K M 
Published: January 2023

Abstract
The Ly-6 alloantigens have been shown to participate in the process of T cell activation based on the ability of anti-Ly-6 mAb to induce IL-2 production and proliferation of T lymphocytes. In the present investigation we have demonstrated that peripheral T lymphocytes from A strain mice exhibited abnormally low proliferative responses after stimulation through Ly-6A/E and Ly-6C molecules when compared to responses of T cells from numerous other mouse strains. The abnormal activation of the Ly-6 pathway of A strain T cells was not due to ineffective FcR cross-linking of the anti-Ly-6 mAb, to inappropriate cellular expression of the Ly-6A/E alloantigen in A strain T cells, or to an active suppressive phenomenon. T lymphocytes from A strain mice proliferated normally when the cells were activated by mAb to Thy-1 or the CD3/TCR complex suggesting that A strain mice did not exhibit a generalized T cell activation defect. Cell separation studies of T cells and accessory cells demonstrated that this defect was quantitative, rather than qualitative, and that it was complex, residing at both the T cell and accessory cell levels. These results suggest that activation of T lymphocytes via the Ly-6 molecule may involve a signaling pathway and/or cell-cell interactions distinct from those required for optimal activation via CD3/TCR.
Hepatic homing of mononuclear inflammatory cells isolated during murine chronic graft-vs-host disease.
Authors: Howell C D , Yoder T , Claman H N , Vierling J M 
Published: January 2023

Abstract
Liver injury in murine chronic graft-vs-host disease (CGVHD) to minor histocompatibility Ag, B10.D2----BALB/c (600 rad), is characterized by mononuclear cell inflammation and necrosis of interlobular bile ducts. Bile duct destruction in this model is similar to that which occurs in human CGVHD, late liver transplant rejection, and primary biliary cirrhosis. This model provides a unique opportunity to isolate mononuclear inflammatory cells from the liver during CGVHD, study their functions, and investigate the immunologic mechanisms responsible for bile duct destruction. In the present study, we compared the in vivo organ homing of mononuclear inflammatory cells (MC) isolated from the liver and spleen during the course of CGVHD. MC isolated from the liver showed a progressive increase in homing to the livers of BALB/c mice from day 7 through 42. In contrast, the hepatic homing of MC isolated from the spleen peaked at day 21 and subsequently declined. CGVHD spleen MC showed a progressive increase in homing to the spleen of BALB/c mice whereas CGVHD liver MC showed no change over time. Homing to other organs was negligible. The hepatic and splenic homing of MC isolated during CGVHD was significantly greater in BALB/c (host) mice than in B10.D2 (donor) mice. Autoradiography was used to determine the intrahepatic sites at which CGVHD liver MC accumulate after i.v. injection into BALB/c mice. The results indicated that MC isolated from the liver when bile duct inflammation is most intense accumulate preferentially in hepatic portal spaces in close proximity to interlobular bile ducts. These results suggest that hepatic homing by CGVHD liver MC is specific for minor histocompatibility Ag expressed on host biliary epithelial cells. These data support the hypothesis that bile duct destruction in murine CGVHD is mediated by MC that are sensitized to minor histocompatibility Ag expressed by host biliary epithelial cells.
Role of the immune response in Sindbis virus-induced paralysis of SJL/J mice.
Authors: Mokhtarian F , Grob D , Griffin D E 
Published: January 2023

Abstract
The pathologic role of the specific immune and inflammatory responses to viral infections of the CNS was investigated by using mice which are susceptible (SJL/J) and resistant (C57Bl6 and BALB/c) to the development of experimental autoimmune encephalomyelitis (EAE). Intracerebral inoculation of 10(4) PFU of Sindbis virus (SV) into 6- to 8-wk-old SJL/J mice resulted in a severe and sometimes fatal encephalomyelitis. A mild to severe hind leg paralysis was observed around days 6 to 7 postinfection (pi) which closely resembled EAE stages and persisted for up to 8 wk pi. Immunosuppression with cyclophosphamide on day 4 alleviated the severity of this disease. Significant perivascular and parenchymal infiltration was present in the brains and spinal cords of SV-infected SJL/J mice for up to 1 mo. This apparent immunopathologic reaction was found to be a characteristic of SJL/J mice, because infection of 6- to 8-wk-old BALB/c and C57Bl6 mice with SV did not cause paralytic disease. These mice also exhibited a significantly milder cellular infiltrate which was mostly resolved on day 12 to 14 pi. Titers of virus in the brain and spinal cords of mice were comparable with clearance by day 7 pi. SV-specific lymphoproliferation and serum antibody responses were also comparable in all mice. SV-infected SJL/J mice developed antibodies to myelin components as demonstrated in Western blots and responded to myelin basic protein by lymphoproliferation. Lymph node cells from these mice, after in vitro challenge with myelin basic protein, transferred a mild EAE-like disease to naive recipients and potentiated subclinical EAE into a severe disease.
Relationship between enterotoxic- and T lymphocyte-stimulating activity of staphylococcal enterotoxin B.
Authors: Alber G , Hammer D K , Fleischer B 
Published: January 2023

Abstract
The enterotoxins produced by Staphylococcus aureus cause a gastrointestinal intoxication probably via their action on intramucosal neuronal cells. Staphylococcal enterotoxins are also the most powerful mitogens known, activating CD3+ T lymphocytes of several species in a clonally variable and MHC class II-dependent fashion. We examined a possible relationship between enterotoxic and mitogenic activity of staphylococcal enterotoxin serotype B (SEB). We used a monoclonal anti-Id directed against the combining site of an anti-SEB mAb. This anti-Id failed to elicit an enteric response by itself but could block the enteric response in monkeys to a 6000-fold excess of SEB. The anti-Id was mitogenic, however, for human and monkey T cells, triggering a fraction of CD4+ and CD8+ T cells. Not all SEB-reactive T cells were activated by the anti-Id. The anti-Id bound to T cells with a similarly low affinity as did SEB. Additional evidence for a separation of enterotoxic and mitogenic activity comes from studies with carboxymethylated SEB. Although this modified SEB had lost its enterotoxic activity, it was as mitogenic as the unmodified molecule. These results support the notion that the enteric reaction to SEB is not mediated via its effect on T lymphocytes. We conclude that SEB and anti-Id might bind to a common structure of different receptors on T cells and target cells in the intestinal mucosa, probably peripheral sensory neurons.
Gene-expression and release of macrophage-colony stimulating factor in quiescent and proliferating fibroblasts. Effects of serum, fibroblast growth-promoting factors, and IL-1.
Authors: Falkenburg J H , Harrington M A , Walsh W K , Daub R , Broxmeyer H E 
Published: January 2023

Abstract
Macrophage (M)-CSF induces the proliferation and differentiation of macrophage-precursor cells, and is an important factor in the survival and activation of mature mononuclear phagocytes. Several effector cell populations such as mononuclear phagocytes, endothelial cells, and fibroblasts, have been reported to produce M-CSF at high levels. We investigated the gene-expression and release of M-CSF in fibroblasts. Quiescent, growth-arrested, fibroblasts showed little expression of M-CSF as demonstrated by Northern blot analysis, and little production of M-CSF as measured in the murine bone marrow bioassay. Initiation of proliferation of fibroblasts by fetal bovine serum was followed by an increase in M-CSF transcription and release of the protein. Similarly, single factors (platelet-derived growth factor) or combinations of factors (epidermal growth factor (EGF) + insulin, platelet-derived growth factor + EGF + insulin, or fibroblast growth factor + EGF + insulin) that induced proliferation of the fibroblasts, also induced increased expression of M-CSF. As soon as 1 h after the addition of fetal bovine serum, M-CSF expression was increased, and reached a plateau at 2 to 8 h after induction. IL-1 increased M-CSF expression both in quiescent and proliferating fibroblasts, and induced the expression and release of granulocyte-, and granulocyte/macrophage-CSF. These results show that expression of M-CSF in fibroblasts is not constitutively at a high level, but undergoes regulation depending on the cellular proliferative state and on further activation by acute response proteins such as IL-1.
CD19 regulation of human B cell responses. B cell proliferation and antibody secretion are inhibited or enhanced by ligation of the CD19 surface glycoprotein depending on the stimulating signal used.
Authors: Callard R E , Rigley K P , Smith S H , Thurstan S , Shields J G 
Published: January 2023

Abstract
The regulation of human B cell proliferation and differentiation by the CD19 surface glycoprotein was investigated. As expected, proliferation induced by costimulation with anti-IgM plus IL-4 or IL-2, or with G28.8 antibody plus IL-4 was inhibited by antibody ligation of CD19. In contrast, proliferation of tonsillar B cells to mitogenic doses of PMA (5 ng/ml) or to EBV were enhanced, and proliferation of B cell lines to BCGF(low) was unaffected. Similarly, specific antibody responses by tonsillar B cells to influenza virus, and Ig secretion by the CESS lymphoblastoid cell line in response to IL-6 were inhibited, whereas polyclonal Ig production in response to EBV was enhanced. These results show that human B cell responses may be inhibited or enhanced by CD19 depending on the stimulating signal used. The difference in response to CD19 ligation did not depend on whether proliferation or differentiation was being measured, or whether stimulation was by surface Ig. In experiments using PMA as a T cell independent mitogen, it was found that ligation of CD19 inhibited proliferation of B cells costimulated with low doses of PMA plus G28.5 (CD40) antibody, but enhanced the response to higher (mitogenic) doses with or without costimulation with G28.5. The change from inhibition to enhancement occurred over a very small increase in PMA dose (0.5-1.0 ng/ml) that corresponded exactly to the lowest dose required for mitogenic activity. Finally, we showed that CD19 ligation inhibited the increase in surface expression of CD23, but not IgM, induced by IL-4, showing that CD19 ligation can have opposed effects on different responses to the same signal. Together our results suggest that CD19 activation of human B cells interacts with other signaling events to enhance or inhibit the subsequent response.
Activation of human phagocytes through carbohydrate antigens (CD15, sialyl-CD15, CDw17, and CDw65).
Authors: Lund-Johansen F , Olweus J , Horejsi V , Skubitz K M , Thompson J S , Vilella R , Symington F W 
Published: January 2023

Abstract
The leukocyte carbohydrate (CHO) Ag CD15, sialyl-CD15, and CDw65 have recently been found to function as ligands for CD62 and ELAM-1 cell adhesion molecules on platelets and endothelium, respectively. Cell adhesion ligands also may act as receptors capable of signal transduction. We therefore investigated the possibility that these CHO Ag and CDw17, a glycolipid Ag whose expression is regulated by leukocyte activation, may have receptor-like characteristics. The effects of antibody cross-linking of CHO Ag on phagocyte activation were measured by using flow cytometry and fluorescent indicators for cytoplasmic calcium ions, oxidative burst, and the granule-associated proteins CD11b and CD67. Cross-linking of CD15, sialyl-CD15, CDw65, or CDw17 induced a moderate release of calcium ions into the cytoplasm of granulocytes, a strong activation of oxidative burst, and a low up-regulation of CD11b and CD67 compared to the effects of treatment with 4 microM FMLP. The results suggest a role for CHO Ag in leukocyte signal transduction and support the view that these molecules are involved in phagocyte activation.
Internalization of a major group human rhinovirus does not require cytoplasmic or transmembrane domains of ICAM-1.
Authors: Staunton D E , Gaur A , Chan P Y , Springer T A 
Published: January 2023

Abstract
Intercellular adhesion molecule-1 (CD54), a cell adhesion molecule and the receptor for the major group of rhinoviruses, is a class 1 membrane protein with five Ig-like domains in its extracellular region, a transmembrane domain, and a short cytoplasmic domain. The amino-terminal domains (D1 and D2) are sufficient for virus binding and the first is most important (1). We have investigated whether other extracellular domains, transmembrane or cytoplasmic domains are required for virus entry as determined by postinfection virion protein biosynthesis. We demonstrate that cytoplasmic, transmembrane, and Ig-like domains 3, 4, and 5 are not essential for rhinovirus entry into transfected COS cells. The efficiency of rhinovirus infection directly correlates with the efficiency of rhinovirus binding and a form of intercellular adhesion molecule-1 that is glycophosphatidyl-inositol anchored, and thus does not extend into the inner leaflet of the membrane bilayer or the cytoplasm efficiently supports virus entry.
Macrophage inflammatory protein 1 modulates macrophage function.
Authors: Fahey T J , Tracey K J , Tekamp-Olson P , Cousens L S , Jones W G , Shires G T , Cerami A , Sherry B 
Published: January 2023

Abstract
Macrophage inflammatory protein 1 (MIP 1), initially purified from the conditioned medium of endotoxin-stimulated macrophages, is a low m.w. heparin-binding protein doublet comprising two peptides, MIP 1 alpha and MIP 1 beta. Although native doublet MIP 1 has previously been shown to exert pyrogenic, mitogenic, and proinflammatory effects on other cell types, its actions on its cell of origin, the macrophage, have not been well catalogued. Our study reports several aspects of macrophage function that are modulated by MIP 1. MIP 1 was not directly cytotoxic for WEHI tumor cells, but MIP 1-treated macrophage exhibited enhanced antibody-independent macrophage cytotoxicity for tumor targets. MIP 1 treatment stimulated proliferation of mature tissue macrophages, and this effect was enhanced upon costimulations with either CSF-1 or granulocyte-macrophage-CSF. Thioglycollate-elicited peritoneal exudate macrophages incubated with native doublet MIP 1-secreted bioactive TNF and IL-6, as well as immunoreactive IL-1 alpha, and these effects were enhanced significantly when the cells were costimulated with IFN-gamma. Purified preparations of the recombinantly derived MIP 1 alpha peptide alone stimulated the secretion of TNF, IL-1 alpha, and IL-6 by peritoneal macrophages, but MIP 1 beta did not. In fact, as little as eightfold excess MIP 1 beta blocked TNF-induction by MIP 1 alpha to a significant degree. By contrast to these apparent "macrophage activating" properties of MIP 1, the cytokine failed to trigger the macrophage oxidative burst, or to up-regulate the expression of Ia on the macrophage surface. Taken together, these data reveal that MIP 1 peptides act as autocrine modulators of their cells of origin, and raise the possibility that MIP 1 peptides may play a role in modulating macrophage responses to inflammatory stimuli in vivo.
The coding sequence of the hemolytically inactive C4A6 allotype of human complement component C4 reveals that a single arginine to tryptophan substitution at beta-chain residue 458 is the likely cause of the defect.
Authors: Anderson M J , Milner C M , Cotton R G , Campbell R D 
Published: January 2023

Abstract
The C4A6 allotype of the human complement component C4 is known to be defective in C5 binding within the C5 convertase. To characterize the position and nature of the molecular defect in the C4A6 allotype we have isolated the C4A6 gene from a cosmid genomic DNA library. Direct sequencing of a 4.4-kb region of the gene covering exons 17 to 31 and encoding the C4d fragment and most of the rest of the alpha chain of C4 revealed that the C4A6 allele encodes the A isotypic residues Pro Cys-Leu Asp at positions 1101, 1102, 1105, and 1106 and the same residues as the C4A3 alpha gene at the polymorphic positions 1054 (Asp), 1157 (Asn), 1182 (Thr), 1188 (Val), 1191 (Leu) and 1267 (Ala). In addition the C4A6 allele was shown to encode a Pro at the previously characterized polymorphic position 707 in the C4a peptide where the C4A3 alpha allele encodes a Leu. The remaining 26 exons of the C4A6 gene were analyzed by detecting nucleotide mismatches in C4A6/C4A3 and C4A6/C4B1 DNA heteroduplexes using the chemical cleavage of mismatch technique. The regions around detected mismatches were sequenced. In total seven nucleotide differences were defined on comparison of the C4A6 and other C4 sequences, of which three were present in exons. Two of these resulted in amino acid changes. One of the amino acid differences is a known polymorphism in C4, a Tyr/Ser substitution at position 328 in the beta-chain. The second amino acid difference caused by a C to T transition in the first base of the codon for amino acid residue 458 was the only one shown to be specific to the C4A6 allotype. The C4A6 allotype contains a Trp residue at this position in the beta-chain instead of the Arg residue found in all other C4A and C4B allotypes so far characterized. We propose that this Arg to Trp substitution at beta-chain residue 458 is responsible for the inability of C4A6 to bind C5 in the C5 convertase.
Expression of c-kit by mesenteric lymph node cells from Nippostrongylus brasiliensis-infected mice and by mast cell colonies developing from these cells in response to 3T3 fibroblast-conditioned medium.
Authors: Leftwich J A , Westin E H , Huff T F 
Published: January 2023

Abstract
Mast cell committed progenitors are nongranulated cells found in mesenteric lymph nodes of mice infected with Nippostrongylus brasiliensis (Nb-MLN) but not from normal mice. Mast cell committed progenitors can respond to either IL-3 or to a factor(s) present in 3T3 fibroblast conditioned media (F-CM) by formation of mast cell colonies. Previous studies from ours and other laboratories suggested that mast cell differentiation involved the W allele product, c-kit, as a receptor and Sl allele product, stem cell factor, as a growth factor. We report here that Nb-MLN cells, which can respond to F-CM by mast cell colony formation, also contain cells that express message for c-kit, and that c-kit message cannot be detected in naive mesenteric lymph node cells, which cannot respond to F-CM. Antisense oligonucleotides to c-kit inhibit mast cell colony formation by Nb-MLN cells in response to F-CM, but not to conditioned medium of PWM-stimulated spleen cells as a source of IL-3. The antisense oligonucleotides also inhibit the degree of granulation by mast cells derived from culture. The results suggest that c-kit and its ligand, stem cell factor, are necessary for mast cell-committed progenitors to proliferate and granulate in response to F-CM but not IL-3.