bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic control of natural resistance to Salmonella typhimurium in mice during the late phase of infection.
Authors: O'Brien A D , Taylor B A , Rosenstreich D L 
Published: January 2023

Abstract
Previous studies have shown that C57L and DBA/2 mice are able to control the initial net growth of Salmonella typhimurium in splenic and hepatic tissues, but when infected i.p., they ultimately succumb to the typhoid-like disease caused by this Gram-negative bacterium. In this investigation, it was observed that the late-phase susceptibility of both the C57L and DBA/2 strains to murine typhoid was not only evident when mice were challenged i.p., but also when mice were challenged subcutaneously, i.v., and orally. Genetic analyses were then performed to characterize the gene or genes responsible for this susceptibility. The results of such experiments were consistent with the hypothesis that a single autosomal recessive gene is primarily responsible for the susceptibility. This gene was distinct from all other previously defined S. typhimurium response genes. The chromosomal location of the late-phase susceptibility gene could not be determined; no linkage was observed between expression of the late-phase susceptible phenotype and selected markers on chromosomes 1, 2, 4, 5, or 7.
Characterization of tick antigens inducing host immune resistance. I. Immunization of guinea pigs with Amblyomma americanum-derived salivary gland extracts and identification of an important salivary gland protein antigen with guinea pig anti-tick antibodies.
Authors: Brown S J , Shapiro S Z , Askenase P W 
Published: January 2023

Abstract
Guinea pigs immunized by subcutaneous injection of an emulsion of incomplete Freund's adjuvant (IFA) containing tick salivary gland extract antigens (SGA) from partially fed female ticks expressed a significant level of tick rejection when challenged 17 days later. This level of tick rejection was similar to animals actively sensitized by tick feeding and challenged at the same time. SGA emulsified with complete Freund's adjuvant (CFA) or administered with saline was ineffective. However, ticks that fed on animals immunized with SGA+IFA or SGA+CFA expressed significant reductions in engorgement weight. SGA was active when prepared with or without protease inhibitors. The minimum effective immunizing dose of SGA was between 100 and 280 micrograms per animal. Extracts made from salivary gland-derived cement material (CA) from partially fed female ticks administered at 50 micrograms in IFA induced levels of tick rejection comparable to animals immunized with 280 micrograms of SGA+IFA. Sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS/PAGE) of 35S- and 125I-radiolabeled SGA and CA extracts immunoprecipitated by guinea pig anti-tick serum that transferred immune resistance demonstrated a unique protein of 20,000 m.w. Serum from animals immunized with SGA+IFA (successful immunization) recognized this same protein, whereas serum from animals immunized with SGA+CFA (unsuccessful immunization) did not. The results of this study suggest that a 20,000 m.w. protein derived from the tick salivary gland may be responsible for the induction and perhaps elicitation of host immune resistance responses to Amblyomma americanum ticks.
Subclasses of rat IgG active in the killing of schistosomula of Schistosoma mansoni in vitro and in vivo.
Authors: Horta M F , Ramalho-Pinto F J 
Published: January 2023

Abstract
Schistosomula of Schistosoma mansoni are known to be killed in vitro by complement and IgG (lethal antibody). To investigate whether this mechanism reflects the in vivo situation, we isolated IgG subclasses from sera of infected rats and assayed their ability to promote the complement-mediated killing of schistosomula in vitro as well as to protect normal recipients from a challenge infection. We found that a serum fraction containing only IgG2a + IgG2b has lethal activity to schistosomula in vitro, whereas a fraction containing only IgG1 + IgG2c fails to kill schistosomula in the presence of complement. The assay of protective activity has shown that the same fraction containing the lethal activity (IgG2a + IgG2b) was able to reduce the number of schistosomula recovered from lungs. These results provide evidence of the participation of IgG2a and/or IgG2b, but not IgG1 or IgG2c, in protective immunity to S. mansoni in rats, possibly through a complement-mediated mechanism.
Macrophage activation to kill Leishmania tropica: characterization of P/J mouse macrophage defects for lymphokine-induced antimicrobial activities against Leishmania tropica amastigotes.
Authors: Nacy C A , Meltzer M S , Fortier A H 
Published: January 2023

Abstract
Macrophages from P/J mice demonstrated both quantitative and qualitative defects in lymphokine (LK)-induced activated macrophage antileishmanial effector reactions: a) these cells recognized the same LK signals that generated resistance to infection in responsive C3H/HeN macrophages, but more signal was required to observe maximal activity; b) LK-induced intracellular destruction of Leishmania tropica by P/J macrophages was minimal (less than 20%), and was induced by only one of three LK signals that regulate antimicrobial activities in C3H/HeN macrophages. The defective microbicidal activity of P/J macrophages observed with LK activation in vitro could also be demonstrated in vivo. Macrophages from P/J mice exposed to the macrophage-activating agent Mycobacterium bovis strain BCG in vivo were capable of restricting the intracellular replication of L. tropica but could not eliminate intracellular parasites, even with further incubation with LK during the 72-hr culture period. The defect of P/J macrophages for intracellular destruction of L. tropica, then, occurred in the activation sequence before the triggering stage that characterizes the macrophage defect of C3H/HeJ mice. Genetic regulation of the P/J macrophage defect appears to be by a single autosomal gene, with defective microbicidal activity as a recessive trait in these animals.
Measles-specific T cell clones derived from a twin with multiple sclerosis: genetic restriction studies.
Authors: Richert J R , McFarland H F , McFarlin D E , Johnson A H , Woody J N , Hartzman R J 
Published: January 2023

Abstract
The association between multiple sclerosis (MS) and HLA-DR2 suggests that the disease may be associated with an aberrant immune response, likely directed against an antigen of either viral or host origin. We have used measles virus-specific T cell clones derived from a patient with MS to study genetic restriction patterns of antigen presentation by macrophage-enriched (E-) populations. Twenty-two clones proliferated in response to measles-infected Vero cells but not to mumps-infected or uninfected Veros. E- cells from both the autologous subject and her healthy, measles nonresponder identical twin were capable of presenting antigen to all clones. Studies with E- cells obtained from a panel of cell donors demonstrated clones which recognized antigen in association with D2/DR2, DR4, subgroups of DR4, and SB3. Three clones recognized antigen only in association with the autologous or twin's cells, but not with other sets of HLA-matched E-cells obtained from healthy donors or from other patients with MS. These studies indicate that the differing responses to measles virus demonstrated by these two identical twins are not explained by alterations in the interactions between antigen-presenting cells and T cells. Furthermore, at the clonal level, no preferential role is seen for HLA-DR2 as the restricting element for presentation of measles virus to these clones.
The in vitro photosensitivity of systemic lupus erythematosus skin fibroblasts.
Authors: Zamansky G B , Minka D F , Deal C L , Hendricks K 
Published: January 2023

Abstract
To investigate the role of DNA damage in the pathogenesis of systemic lupus erythematosus (SLE), we studied the ability of skin fibroblasts derived from SLE patients to recover from ultraviolet (UV) light radiation of varying wavelengths. Four of five SLE cell strains were more sensitive to UV-C (254 nm), sun lamp, and UV-A (320 to 400 nm) light than were normal cells. SLE cellular recovery was most sensitive to broad spectrum, long wavelength light. This hypersensitivity did not appear to result from the UV light activation of a clastogenic factor. Experiments which examined the DNA repair capacity of irradiated cells indicated that SLE fibroblasts may be able to excise certain DNA lesions as well as normal cells. The mechanisms responsible for the hypersensitivity of SLE cells remain under investigation.
Idiotypic analysis of polyclonal and monoclonal anti-p-azophenylarsonate antibodies of BALB/c mice expressing the major cross-reactive idiotype of the A/J strain.
Authors: Leo O , Slaoui M , Marvel J , Milner E C , Hiernaux J , Moser M , Capra J D , Urbain J 
Published: January 2023

Abstract
The idiotypic cascade allows the induction of silent idiotypes, and as such, the immune system can be reprogrammed towards predetermined goals. To understand the genetic origin of silent idiotypes, we have used a system in which detailed structural and genetic information is available. The major cross-reactive idiotype (CRIA) of A/J mice (positive strain) immunized with arsonate coupled to a carrier can be regularly induced in BALB/c mice (negative strain) by anti-idiotypic treatment with or without subsequent antigen immunization. By using a panel of monoclonal anti-idiotypic antibodies, we have found that the germline-encoded CRIA displays a mosaic of at least five idiotopes. Polyclonal and monoclonal anti-arsonate antibodies prepared from idiotypically manipulated BALB/c mice have been studied. Four germline idiotopes are shared between the CRIA of the A/J strain and the CRIA-like idiotype induced in BALB/c mice. Furthermore, CRIA-like antibodies can appear "spontaneously" in some BALB/c mice immunized with antigen only. The data suggest that anti-idiotypic treatment in BALB/c mice selects a preexisting subset of antibodies. From the serological analysis, it is predicted that CRIA molecules from A/J and CRIA-like molecules from BALB/c employ different VH subgroups but share some components of the hypervariable regions. These predictions are tested in a forthcoming paper that describes the amino acid sequences of BALB/c monoclonal antibodies displaying the major cross-reactive idiotype of the A/J strain.
The fate of IgE bound to rat basophilic leukemia cells. IV. Functional association between the receptors for IgE.
Authors: Furuichi K , Rivera J , Triche T , Isersky C 
Published: January 2023

Abstract
Rat basophilic leukemia cells (RBL-2H3) have receptors for immunoglobulin E (IgE) and immunoglobulin G (IgG). These receptors for IgE mediate the endocytosis of chemically or immunochemically cross-linked IgE but not monomeric IgE. However, unoccupied receptors were endocytosed with cross-linked IgE. To further assess the degree and specificity of the observed coendocytosis, we exposed cells carrying monomeric rat IgE and monomeric mouse IgE anti-DNP to a DNP-protein conjugate. We found that up to 30% of the surface-bound monomeric rat IgE redistributed at 0 to 4 degrees C and was then internalized at 37 degrees C with the immunochemically cross-linked mouse IgE. To assess the specificity of the coendocytosis, we exposed cells carrying monomeric rat IgE to immunochemically cross-linked mouse IgG. We found that the binding, patching, and endocytosis of cross-linked mouse IgG had no effect on the monomerically bound rat IgE. The rate of coendocytosis was the same as the rate of endocytosis (t 1/2 3 to 5 min). The extent of coendocytosis depended on the extent of endocytosis but was relatively insensitive to changes in the ratio between mouse and rat IgE over a broad range. These results indicate that some of the receptors for IgE are associated in a specific fashion.
Evidence that autoreactive T hybridomas recognize multiple epitopes on the I-Ak molecule.
Authors: Glimcher L H , Serog B , McKean D J , Beck B N 
Published: January 2023

Abstract
In this study we attempt to define the number of determinants on the I-Ak molecule recognized by a panel of autoreactive I-Ak-specific T cell hybridomas. The recognition sites or histotopes of a panel of autoreactive I-Ak-restricted T cell hybridomas was determined in two ways: 1) by their ability to be activated by a panel of A betak and A alphak mutant antigen-presenting cell lines, and 2) by inhibition of activation by anti-I-Ak monoclonal antibodies. The results are most consistent with the presence of multiple distinct recognition sites on the I-Ak molecule. However, an alternative explanation, that the T cell hybridomas recognize the same self epitope on Class II molecules, but with different affinity, cannot be excluded.
Characterization of one polypeptide antigen potentially related to protective immunity against the blood infection by Plasmodium falciparum in the squirrel monkey.
Authors: Jendoubi M , Dubois P , Da Silva L P 
Published: January 2023

Abstract
We have previously demonstrated that squirrel monkeys vaccinated with a particular protein fraction of Plasmodium falciparum develop a protective immunity that is expressed at the humoral level by the presence of antibodies directed essentially against two parasite proteins. We have now isolated a mAb that recognizes one of these polypeptides of an apparent m.w. of 90,000 and an isoelectric point of 6.2. This parasite protein is synthesized in a short period of the asexual blood cycle corresponding to the mature tropho and early schizont stages, but is stable up to the end of the schizogony. By immunofluorescence analysis, the protein seems to be located essentially at the surface of the parasite and/or in the parasitophorous vacuole. The protein is degraded or modified in the process of reinvasion, because it was not detected in merozoites or in newly invaded RBC. Monoclonal antibody XIV-7 has no inhibitory effect against the parasite in vitro.
Induction of monocyte procoagulant activity with OKT3 antibody.
Authors: Iitaka M , Iwatani Y , Row V V , Volpé R 
Published: January 2023

Abstract
OKT3 monoclonal antibody (MoAb), a mouse MoAb against cluster of differentiation 3 (CD3) molecule, induced a large amount of procoagulant activity (PCA) in human peripheral blood mononuclear cells (PBM). The PCA-inducing capability in OKT3 MoAb was abolished by absorption with T lymphocytes or Sepharose-conjugated antibody to mouse IgG. Most of the PCA in PBM was associated with monocytes. There was a dose-dependent increase in PCA when increasing numbers of T cells were added to the monocytes in the presence of OKT3 MoAb. OKT3 MoAb did not induce PCA in either T cells or monocytes alone. T cells pulsed with OKT3 MoAb only in the presence of monocytes could induce PCA in monocytes. Culture supernatants (CS) from PBM stimulated with OKT3 MoAb did not enhance PCA in monocytes; however, it did induce PCA in the human monocyte-like cell line (U937) which differs in some properties from monocytes; this activity could be abolished by the MoAb against human interferon-gamma (IFN-gamma). Nevertheless, neither human IFN-gamma nor interleukin 1 or 2 had significant direct effect in inducing PCA in U937 cells; CS from either monocytes or T cells alone stimulated with OKT3 MoAb did not induce PCA in U937 cells. This apparent discrepancy suggests that there may be factors in CS that induce PCA in U937 cells only in the presence of IFN-gamma. The PCA induced in monocytes or U937 cells was tissue factor-like because of the dependence on coagulation factors V, VII, and X. These observations suggest that OKT3 MoAb is a potent T cell-dependent monocyte PCA inducer and stimulates T cells only in the presence of monocytes. The direct cellular interaction between monocytes and stimulated T cells appears to be necessary to elicit monocyte PCA with OKT3 MoAb stimulation. Thus, monocytes may play a dual role, not only as effector cells, but also as cells that collaborate with T cells after OKT3 MoAb stimulation so as to produce PCA.
IgG3 is the major source of cryoglobulins in mice.
Authors: Abdelmoula M , Spertini F , Shibata T , Gyotoku Y , Luzuy S , Lambert P H , Izui S 
Published: January 2023

Abstract
A total of 20 of 23 IgG3 mAb derived from unmanipulated autoimmune MRL/MpJ-lpr/lpr mice was shown to generate cryoglobulins which were composed exclusively of IgG3. Although three IgG3 mAb failed to develop cryoglobulins, they were able to bind nonspecifically to any IgG3 molecules as efficiently as cryoprecipitable IgG did. The direct role of the gamma 3 constant region for the generation of cryoglobulins was demonstrated by the following findings: 1) the cryoglobulin activity was independent of the specificity of the IgG3 mAb, 2) no mAb other than those of the IgG3 subclass, including IgM rheumatoid factors (RF), generated cryoglobulins, and 3) the cryoglobulin activity was gained after the Ig class switch of mAb from IgM to IgG3. Analysis of Ig components in three different sources of cryoglobulins, either induced by the injection of bacterial LPS or by the infection with Plasmodium yoelii in BALB/c mice or developed spontaneously in MRL/MpJ-lpr/lpr mice, revealed the selective concentration of IgG3 in these cryoglobulins; greater than 99%, 73% and 58% of IgG recoverable from these three cryoglobulins, respectively, were IgG3. This further attests to the major role of IgG3 in the generation of cryoglobulins in mice. In addition, the enhanced formation and even induction of IgG3 cryoglobulins in the presence of IgM anti-IgG3 RF mAb, and the enrichment of IgM RF in LPS- or malaria-induced cryoglobulins indicated that IgM RF can be involved in the generation of cryoglobulins by interacting with noncryoprecipitable IgG3 as well as cryoprecipitable IgG3.
Therapy with monoclonal antibodies. An in vivo model for the assessment of therapeutic potential.
Authors: Isaacs J D , Clark M R , Greenwood J , Waldmann H 
Published: January 2023

Abstract
A set of rat-human and rat-rat chimeric mAb has been created, all possessing V regions identical in their specificity for the mouse CD8 Ag. In vitro all antibodies were able to block cell-mediated lysis but varied greatly in their capacity to utilize rabbit complement. We examined the ability of these chimeric antibodies to deplete in vivo and established a clear hierarchy. Of the human IgG subclasses, only IgG1, 2, and 3 could fix complement in vitro, yet all (IgG1-4) were remarkably potent at depleting CD8+ PBL in vivo. In contrast, human IgA2 and IgE were ineffective at clearing CD8+ PBL. The vector system used to create these antibodies together with the small doses of antibodies required to deplete in vivo make this a simple and rapid system for testing the effects of different antibody isotypes and mutants. We have shown that a mutant of human IgG1, which is incapable of fixing complement, depletes perfectly well in vivo, whereas an aglycosyl IgG1 mutant is rendered inactive. Our model provides a unique opportunity to study effector functions and motifs that are used by mAb in vivo and will help in the design of improved antibodies for human therapy.
Protein Arp and protein H from group A streptococci. Ig binding and dimerization are regulated by temperature.
Authors: Akerström B , Lindahl G , Björck L , Lindqvist A 
Published: January 2023

Abstract
Cell surface proteins that bind to the Fc part of Ig are expressed by many strains of group A streptococci, an important human pathogen. Two such bacterial strains, AP4 and AP1, were shown to bind IgA and IgG, respectively, in a temperature-dependent manner. The binding of radiolabeled Ig to the bacterial cells was lower at 37 degrees C than at 22 and 4 degrees C. Similarly, protein Arp, the IgA-binding protein isolated from strain AP4, and protein H, the IgG-binding protein isolated from strain AP1, displayed a strong Ig-binding at 22 degrees C and lower temperatures, and virtually no binding at all at 37 degrees C. The effect was reversible: lowering of the temperature restored the binding and vice versa. A gradual shift between binding and nonbinding took place between 27 and 37 degrees C. Gel chromatography and velocity sedimentation centrifugation showed that protein Arp and protein H appeared as noncovalently associated dimers at 10 and 22 degrees C, and as monomers at 37 degrees C. These results strongly suggest that the dimerization of protein Arp and protein H, rather than the low temperature itself, yielded the strong Ig-binding of the proteins at 10 and 22 degrees C. Indeed, after covalent cross-linking of the dimers at 10 degrees C by incubation with low concentrations of glutaraldehyde, full Ig-binding was achieved even at 37 degrees C. A carboxyl-terminal proteolytic fragment of protein Arp, which completely lacked the IgA-binding capacity at any temperature, showed the same temperature-dependent dimerization as intact protein Arp, suggesting that the Ig-binding part of the protein is not required for dimerization. The implications of these results for the function of Ig-binding group A streptococcal proteins, and their role in the host-parasite relationship are discussed.
Regulation of usage of membrane and secreted 3' termini of alpha mRNA differs from mu mRNA.
Authors: Lebman D A , Park M J , Fatica R , Zhang Z 
Published: January 2023

Abstract
Previous studies demonstrated that the addition of transforming growth factor-beta (TGF-beta) to LPS-stimulated B cell cultures induced cells to express membrane IgA and to mature to IgA-secreting cells without a parallel change in usage of 3' termini by alpha mRNA. In these cultures, the secreted form of alpha mRNA was predominant even before expression of membrane IgA could be detected. In the present study, we demonstrate that the preferential usage of the secreted terminus of alpha mRNA in these cultures is not caused by transcription termination and reflects a difference in the regulation of choice of 3' terminus for alpha and mu mRNA. The addition of TGF-beta to LPS-stimulated cultures causes an increase in the steady state level of alpha mRNA using the secreted 3' terminus. In contrast, TGF-beta decreases the steady state level of mu mRNA and inhibits usage of the 3' terminus for the secreted form of mu, suggesting that the choice of 3' terminus for alpha and mu mRNA is regulated differently in LPS-stimulated cultures. To determine whether the difference in usage of 3' termini by alpha and mu mRNA was a property of the culture system or whether it reflected a difference in regulation, C alpha was transfected into cell lines representing different stages of B cell development. The secreted form of alpha mRNA predominates regardless of the ratio of membrane to secreted forms of the endogenous C mu gene. A similar dichotomy in 3' terminus usage occurred in a stable C alpha transfectant of the BCL1 lymphoma, suggesting that trans-acting factors are not limiting. Furthermore, as was the case with normal B cells, the predominance of the secreted form of the transfected C alpha genes was not due to transcription termination. These data demonstrate that usage of 3' terminus in alpha and mu mRNA is regulated differently.