bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiviral immune responses of fully allogeneic irradiation bone marrow mouse chimeras.
Authors: Fang L B , Gessner A , Kühlcke K , Gossmann J , Lehmann-Grube F 
Published: December 2022

Abstract
In (B10.BR----B10) chimeras infected with lymphocytic choriomeningitis (LCM) virus higher titers were attained in spleens and livers than in organs of the mice used for their construction, and the subsequent elimination was retarded, but eventually the virus was cleared. The numbers of LCM virus-specific CTL and their precursors as quantitated with chromium-release assay and limiting dilution method, respectively, were lower in chimeras than in B10.BR or C57BL/10J mice, and fewer were restricted for the haplotypes of the donors than of the recipients. The same was true with regard to antiviral effector cells, which were determined by adoptive immunization. The numbers of spleen cells releasing IgM and IgG antiviral antibodies were virtually as high in chimeras as they were in C57BL/10J and B10.BR mice. Transfer of immune splenocytes from either B10.BR or C57BL/10J mice resulted in incomplete virus elimination from the spleens of infected chimeras, whereas injection of a mixture of the two types of immune cells led to efficient clearance. We conclude that in the chimeras cells of both donor and recipient haplotypes participate in the infection, which is terminated by H-2k- and H-2b-restricted T lymphocytes that these animals are capable of generating. We conclude, furthermore, that clearance of the LCM virus from the tissues requires contact between effector and target cells.
Antibody-dependent enhancement of dengue virus infection mediated by bispecific antibodies against cell surface molecules other than Fc gamma receptors.
Authors: Mady B J , Erbe D V , Kurane I , Fanger M W , Ennis F A 
Published: December 2022

Abstract
It is known that antibodies to dengue viruses at subneutralizing concentrations enhance dengue virus infection of Fc gamma R+ cells. This phenomenon called antibody-dependent enhancement (ADE) occurs when virus-antibody complexes bind to the Fc gamma R via the Fc portion of the Ig. It has been hypothesized that ADE may be responsible for the pathogenesis of the severe manifestations of dengue virus infection including dengue hemorrhagic fever/dengue shock syndrome. To further analyze the mechanisms of ADE, we prepared bispecific antibodies by chemically cross-linking antidengue virus antibodies to antibodies specific for Fc gamma RI or Fc gamma RII and the non-Fc R molecules beta2 microglobulin, CD15 or CD33 and examined whether these bispecific antibodies could enhance infection. Bispecific antibodies targeting dengue virus to Fc gamma RI or Fc gamma RII enhanced dengue virus infection, consistent with previous reports using conventional antibodies. Furthermore, bispecific antibodies targeting dengue virus to beta2 microglobulin, CD15 or CD33 also enhanced dengue virus infection. Bispecific antibody mediated ADE was inhibited by pretreating the cells with the appropriate blocking mAb. These results indicate that cell surface molecules other than Fc gamma R can mediate ADE and suggest that the Fc gamma R does not provide a unique signal necessary for enhanced infection. We hypothesize that directing dengue virus to the cell surface by a bispecific antibody facilitates the interaction between dengue virus and its receptor, thereby increasing its infectivity.
An HIV-1-infected T cell clone defective in IL-2 production and Ca2+ mobilization after CD3 stimulation.
Authors: Perez V L , Rowe T , Justement J S , Butera S T , June C H , Folks T M 
Published: December 2022

Abstract
A chronically HIV-1-infected T cell clone (J1.1) derived from Jurkat cells was developed that possesses defects in CD3 signaling. This clone was phenotypically determined to be CD4- and express a reduced surface density of CD3 as compared with a pool of uninfected Jurkat clones. Although J1.1 could be induced with TNF-alpha to produce HIV-1 particles, stimulation via the CD3 (T3-Ti) complex, using mAb cross-linking, had no effect on viral production. Further investigation revealed that J1.1 secreted approximately 20-fold less IL-2 than did uninfected Jurkat cells after anti-CD3 treatment. In addition, a separate defect in Ca2+ mobilization was noted in the HIV-1-infected J1.1 line when compared with uninfected Jurkat cells after anti-CD3 cross-linking. The cell line described offers a new model in which to study the mechanisms of several defects directly imposed by HIV-1 on CD3+ cells.
IFN-gamma modulates the early development of Th1 and Th2 responses in a murine model of cutaneous leishmaniasis.
Authors: Scott P 
Published: December 2022

Abstract
Resistance to Leishmania major in mice is associated with the generation of distinct CD4+ Th subsets, termed TH1 and TH2. To define the factors contributing to the genesis of these Th cells, we first investigated when these subsets developed following L. major infection. Lymph node (LN) cells collected 3 days after infection of BALB/c mice secreted IL-4 and IL-5 in vitro, but little IFN-gamma, whereas LN cells from a resistant strain, C3H/HeN, secreted IFN-gamma and no IL-4 or IL-5. Cytokine production was eliminated in both cases by in vivo or in vitro depletion of CD4+ cells, but not after depletion of CD8+ cells. Similar responses were observed after inoculation of killed promastigotes or a soluble leishmanial Ag preparation. These data indicate that the development of Th1- and Th2-like responses can precede lesion formation and does not require a live infection. We next investigated whether IFN-gamma was important in the differentiation of Th1 and Th2 cells. C3H/HeN mice have previously been shown to be susceptible to leishmanial infection after treatment with anti-IFN-gamma. We confirmed this observation and found that the abrogation of resistance was associated with enhanced production of IL-4 and IL-5, and decreased production of IFN-gamma by cells taken from these mice. Conversely, LN cells from BALB/c mice inoculated with parasites plus IFN-gamma produced significantly higher levels of IFN-gamma, and decreased levels of IL-4 and IL-5, than mice infected with parasites alone. Finally, we determined if IFN-gamma might augment vaccine induced immunity. We found that s.c. immunization with soluble leishmanial Ag, the bacterial adjuvant, Corynebacterium parvum and IFN-gamma could protect mice against L. major infection, and that this protection was associated with induction of Th1 responses. From these data we conclude that levels of IFN-gamma at the time of infection or immunization dramatically alters the type of response elicited: high levels of IFN-gamma favor Th1 type responses, whereas low levels promote a Th2 response.
Transrearrangements between antigen receptor genes in normal human lymphoid tissues and in ataxia telangiectasia.
Authors: Kobayashi Y , Tycko B , Soreng A L , Sklar J 
Published: December 2022

Abstract
The polymerase chain reaction (PCR) was used on DNA obtained from various normal lymphoid tissues to amplify chimeric TCR gene rearrangements involving J segments of the beta gene and V segments of the gamma or delta genes. As found previously for the transrearrangements between the gamma and delta genes, transrearrangements involving the beta gene were more abundant in DNA of the thymus than in DNA of the spleen, lymph node, bone marrow, or PBL. In addition, transrearrangements between Ig H chain V region segment and J segment of TCR delta chain were also found in DNA of normal thymus. Sequence analysis of the trans-rearrangement PCR products revealed structures closely resembling normal intragenic rearrangements, with N insertions and often D segments at the junctions between segments. The sequences analyzed suggest that transrearrangements arise through the action of normal lymphocyte recombinase, involve trans recognition of heptamer/nonamer recombination signals, and follow the 12 + 23 spacer rule. To test whether transrearrangements result from chromosomal rearrangements with breakpoints at the sites of Ag receptor genes, PCR was performed on the DNA of PBL from patients with ataxia telangiectasia, a disorder in which circulating lymphocytes often have numerous karyotypic abnormalities with breakpoints at the cytogenetic positions of these genes. Comparison of the results of PCR on this DNA and that of normal tissues demonstrated a substantially increased frequency for most types of transrearrangements investigated. These results support the interpretation that transrearrangement among TCR genes may occur by chromosomal rearrangement.
Allelic exclusion of a T cell receptor-beta minilocus.
Authors: van Meerwijk J P , Iglesias A , Hansen-Hagge T , Bluethmann H , Steinmetz M 
Published: December 2022

Abstract
A TCR-beta minilocus in germline configuration (beta M) has previously been shown to undergo rearrangement and expression in transgenic mice. To study allelic exclusion of TCR miniloci, several beta M transgenic mouse lines were generated and crossed with mice transgenic for a functionally rearranged TCR V beta 2 gene (beta R). PCR analysis of beta M beta R double transgenic mice revealed almost complete suppression of endogenous TCR V beta gene rearrangements, but blockage of minilocus V beta rearrangements was achieved with only one of five minilocus transgenic lines. This result cannot be explained by copy number or arrangement of the multiple miniloci integrated. It appears that the minilocus is not autonomously regulated which suggests that sequences flanking the integration sites influence accessibility of the minilocus for rearrangement and allelic exclusion. However, although productively rearranged genes were formed in double transgenic mice, surface expression of minilocus-encoded beta chains was not detected. This indicates that allelic exclusion may operate at a level after gene rearrangement.
Lipopolysaccharide-induced inhibition of scavenger receptor expression in human monocyte-macrophages is mediated through tumor necrosis factor-alpha.
Authors: van Lenten B J , Fogelman A M 
Published: December 2022

Abstract
The exposure of mononuclear cells to LPS results in a variety of cellular alterations including changes in the expression of various membrane receptors. In human monocyte-macrophages the development of the scavenger receptor, which mediates the uptake and internalization of chemically modified proteins, was suppressed by 100 ng/ml of LPS, concomitant with a reduction in receptor mRNA. Removal of LPS from the media resulted in a rapid increase in scavenger-receptor activity and mRNA that was further enhanced by macrophage-CSF and granulocyte/macrophage-CSF. However, neither macrophage-CSF nor granulocyte/macrophage-CSF could overcome the suppression of scavenger-receptor activity in the presence of LPS. The LPS-induced suppression of the scavenger receptor could be overcome by the co-addition of neutralizing antibody to TNF-alpha. TNF-alpha added to human monocyte-macrophages in the absence of LPS suppressed scavenger receptor activity to the same extent as did LPS. In contrast, the co-addition of LPS and neutralizing antibodies to either IFN-gamma or to IL-1 beta did not overcome the inhibitory effects of LPS on scavenger receptor activity. We conclude that the LPS-induced suppression of the scavenger receptor is mediated primarily through TNF-alpha.
IL-1 increases phospholipase A2 activity, expression of phospholipase A2-activating protein, and release of linoleic acid from the murine T helper cell line EL-4.
Authors: Bomalaski J S , Steiner M R , Simon P L , Clark M A 
Published: December 2022

Abstract
The early events in IL-1-mediated activation of T cells were investigated in the murine T cell line, EL-4. Treatment of EL-4 cells with human rIL-1 beta resulted in a rapid increase in phospholipase A2 (PLA2) activity. PLA2 activity increased approximately fivefold within 4 min after exposure to IL-1. Synthesis of the phospholipase A2- activating protein (PLAP) and its mRNA were also increased within 4 min of IL-1 treatment and preceded the increase in PLA2 enzyme activity. The increases in PLA2 activity and PLAP protein and mRNA levels were all transient and declined to baseline within 10 min after the addition of IL-1. The changes in levels of PLAP as a function of time after IL-1 treatment were consistent with PLAP playing an important role in the regulation of PLA2 activity in this system. The consequence of the elevated PLA2 activity was examined by analysis of the fatty acids released from IL-1-treated cells. There was a 20-fold increase in the release of radioactivity from [14C]-linoleic acid labeled cells whereas there was very little change in the release of radioactivity from [14C]-arachidonic acid labeled cells in response to the addition of IL-1. The radioactivity released from [14C]-linoleic acid labeled cells was analyzed by HPLC; no conversion of radiolabeled linoleic into arachidonic acid was observed. In EL-4 cells, IL-1 potentiates PMA-mediated release of IL-2 at suboptimal concentrations of PMA. Linoleic acid also augmented PMA-induced IL-2 release from the EL-4 cells. This fatty acid was more than 10 times more effective than arachidonic acid in this regard. Furthermore, the addition of exogenous PLAP to EL-4 cells could substitute for IL-1 in the stimulation of IL-2 release. These results suggest that the IL-1 effects on T cells may be mediated at least in part through increased PLA2 activity due to increased synthesis of PLAP. Furthermore, the release of the unsaturated fatty acid linoleic acid or its metabolites may be of functional importance in IL-1-mediated IL-2 production by EL-4 cells.
Endogenous loading of HLA-A2 molecules with an analog of the influenza virus matrix protein-derived peptide and its inhibition by an exogenous peptide antagonist.
Authors: Gammon M C , Bednarek M A , Biddison W E , Bondy S S , Hermes J D , Mark G E , Williamson A R , Zweerink H J 
Published: December 2022

Abstract
Episomal plasmids (p8901) with minigenes coding for the influenza virus matrix peptide amino acids 57-68 (KGILGFVFTLTV; referred to as M57-68) or coding for a modified peptide were introduced into HLA-A2-positive target cells. The association of these peptides, synthesized in the cytoplasm, with HLA-A2 and the expression of this complex at the cell surface was evaluated with HLA-A2-restricted CTL specific for the influenza virus matrix peptide M57-68. Cells expressing M57-68 were lysed effectively, as were cells expressing a peptide that retained residues 60-64 with seven flanking alanine residues (AAALGFVFAAAA). An exogenously added synthetic analog of peptide M57-68 that inhibited sensitization of targets with synthetic peptide M57-68 also inhibited lysis of cells expressing the minigene coding for the peptide with seven alanine substitutions. These results demonstrate the utility of minigene DNA constructs in creating experimental systems to develop agents to diminish the severity of CTL-mediated tissue damage in autoimmune diseases and graft rejection.
Inhibition of tumor necrosis factor (TNF)-mediated NF-kappa B activation by selective blockade of the human 55-kDa TNF receptor.
Authors: Kruppa G , Thoma B , Machleidt T , Wiegmann K , Krönke M 
Published: December 2022

Abstract
The numerous biologic activities of TNF appear mediated by two types of specific cell surface receptors of 55 to 60 kDa (TR55) and 75 to 80 kDa (TR75) molecular mass, respectively. The role of TR55 in the activation of the nuclear transcription factor kappa B (NF-kappa B) was investigated using an antagonistic, mAb, H398, specific for the human TR55. The human leukemic T cell line, Jurkat, which expresses both types of receptors at comparable levels, was used to test for NF-kappa B activation by electrophoretic mobility shift assays using as a probe an oligonucleotide encompassing the two tandemly arranged kappa B sites of the HIV-1 LTR enhancer. mAb H398 is shown to efficiently block not only TNF- but also lymphotoxin-mediated activation of NF-kappa B. Furthermore mAb H398 also impeded TNF- or lymphotoxin-mediated activation of chloramphenicol acetyl transferase gene expression from the HIV-1-LTR as determined by transient transfection assays. These findings indicate that both, induction of NF-kappa B binding to DNA, and transcriptional activity can be efficiently inhibited by selective blockade of TR55. Finally it is shown, that human TR55 confers NF-kappa B inducibility when expressed in the mouse pre-B cell line 70Z/3, which does not respond to TNF in its parental state. Together, the results of this study indicate that TR55 is both necessary and sufficient for mediating TNF activation of NF-kappa B.
Two additional human serum proteins structurally related to complement factor H. Evidence for a family of factor H-related genes.
Authors: Skerka C , Timmann C , Horstmann R D , Zipfel P F 
Published: December 2022

Abstract
We identify and characterize two human serum proteins with an apparent molecular mass of 24 and 29 kDa, which are antigenically related to complement factor H. These proteins represent differently glycosylated forms and are encoded by the same mRNA. The corresponding cDNA clone is 1051 bp in size and hybridized to a 1.4-kb mRNA derived from human liver. The predicted translation product represents a protein of 270 amino acids, which displays a hydrophobic leader sequence, indicative of a secreted protein. The secreted part is organized in four short consensus repeats (SCR) and has a single putative N-linked glycosylation site. This predicted sequence is closely related to that of the previously described factor H-related proteins h37 and h42, which are also derived from a 1.4-kb mRNA. Amino acid comparison of these factor H-related proteins showed identical leader sequences, an exchange of three amino acids in SCR1, identical sequences of SCR2, and a lower degree of homology between SCR3-4 (h24 and h29) and SCR4-5 (h37 and h42). In addition, SCR3-4 of h24 and h29 display homology to SCR19-20 of human complement factor H. The relatedness of structural elements of the factor H-related proteins h24, h29, h37, and h42 and of factor H, suggests a function common to these proteins and indicates the existence of a gene family consisting of factor H and at least two factor H-related genes.
Processing of exogenous liposome-encapsulated antigens in vivo generates class I MHC-restricted T cell responses.
Authors: Collins D S , Findlay K , Harding C V 
Published: December 2022

Abstract
Acid-sensitive liposomes have been developed for cytosolic delivery of encapsulated substances. We now demonstrate delivery of liposome-encapsulated Ag into the class I MHC Ag processing pathway in peritoneal macrophages in vitro using several types of acid-sensitive liposomes, including those composed of dioleoylphosphatidylethanolamine (DOPE)/palmitoylhomocysteine, DOPE/cholesterol hemisuccinate, DOPE/dioleoylsuccinylglycerol, and DOPE/dipalmitoylsuccinylglycerol. Our previous studies showed that acid-resistant liposomes (dioleoylphosphatidylcholine/dioleoylphosphatidylserine) did not engender class I-mediated presentation in vitro. However, in vivo immunization with OVA encapsulated in acid-resistant as well as acid-sensitive liposomes generated class I MHC-restricted T cell responses, as determined by subsequent in vitro cytotoxicity assays using OVA-transfected target cells. Target lysis by these cells was OVA- and class I MHC (Kb)-specific. This response was not generated by immunization with equivalent amounts of soluble OVA. Thus, a pathway for in vivo class I processing of Ag encapsulated in acid-resistant liposomes has been missed in vitro, perhaps because it is dependent on specific populations of APC or interactions between cells that have not been reconstituted in vitro. This pathway may explain the ability of many exogenous particulate Ag (liposomes, bacteria, parasites, and mammalian cells) to generate class I MHC-restricted T cell responses.
T-deficient transmembrane signaling in CD4+ T cells of retroviral-induced immune-deficient mice.
Authors: Fitzpatrick E A , Bryson J S , Rhoads C , Kaplan A M , Cohen D A 
Published: December 2022

Abstract
The defective virus found in the LP-BM5 mixture of murine leukemia viruses induces a severe immune deficiency disease in C57BL/6 mice that is characterized by the activation and expansion of T and B cells that become unresponsive to normal immune stimuli. The nature of the biochemical lesion in these defective lymphocyte populations remains unknown. Flow cytometric analysis of the T cell population in infected animals has demonstrated expansion of both CD4+ and CD8+ subsets. Despite chronic expansion in vivo, CD4+ T cells by wk 4 postinfection failed to up-regulate cell surface IL-2R expression, produced IL-2, or proliferate in vitro in response to either Con A, Staphylococcal enterotoxin super-antigens, or anti-CD3 stimulation. Exogenous IL-2 did not restore the proliferative response and also failed to up-regulate IL-R expression on CD4+ T cells from infected mice, even though basal IL-2R expression was initially elevated compared to normals. In contrast, CD4+ T cells from infected mice could be induced to proliferate by stimulation with PMA and ionomycin resulting in IL-2R up-regulation, IL-2 production, and proliferation. Moreover, proliferation could also be induced by anti-CD3 plus PMA, although anti-CD3 plus ionomycin was without effect. These studies suggest that chronic expansion of CD4+ T cells in infected mice is probably not maintained by normal TCR signaling, which appears defective in these cells. In addition, the lesion in biochemical signaling appears to result in defective activation of protein kinase C, which can be overcome by direct activation with PMA.
Stimulation of mouse connective tissue-type mast cells by hemopoietic stem cell factor, a ligand for the c-kit receptor.
Authors: Takagi M , Nakahata T , Kubo T , Shiohara M , Koike K , Miyajima A , Arai K , Nishikawa S , Zsebo K M , Komiyama A 
Published: December 2022

Abstract
The proliferative capacity of mouse connective tissue-type mast cells (CTMC) was analyzed by using a newly discovered c-kit ligand, termed stem cell factor (SCF). More than 90% of CTMC in the peritoneal cavity responded to recombinant rat SCF (rrSCF) and were able to give rise to pure mast cell colonies in methylcellulose culture. Serial observation (mapping) of growth of individual CTMC in culture containing rrSCF confirmed their striking proliferative ability. No serum but accessory cells (non-CTMC cells) in the peritoneal population were required for the clonal growth of CTMC induced by rrSCF in our methylcellulose culture of whole peritoneal cells. The rrSCF-induced mast cell colony formation from peritoneal CTMC was completely inhibited by the addition of anti-c-kit antibody, which can block the binding of SCF to c-kit, to the culture. When IL-3 was combined with rrSCF, mast cell colonies dramatically increased in size. Mapping studies revealed that the combination of the two factors augmented the proliferative rate of CTMC. Approximately 60% of the constituent cells of the mast cell colonies which were formed from peritoneal CTMC in the culture containing rrSCF alone were stained with berberine sulfate, which is a characteristic of CTMC. However, most mast cells which were induced by rrSCF+IL-3 from peritoneal CTMC contained berberine(-)-safranin(-)-Alcian blue(+) granules. Although IL-4 exhibited little synergism with rrSCF in the induction of CTMC proliferation, the addition of IL-4 to the culture containing rrSCF+IL-3 resulted in an increase in mast cells which retained CTMC characteristics.