bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of antioxidants on primary alloantigen-induced T cell activation and proliferation.
Authors: Chaudhri G , Clark I A , Hunt N H , Cowden W B , Ceredig R 
Published: December 2022

Abstract
Because oxygen-centered free radicals are involved in cell-mediated immune responses, we examined the possibility that these reactive species could also have a role in the lymphoproliferative response to alloantigens in the mixed lymphocyte culture (MLC). Three classes of agents that prevent the formation, or damaging effects, of oxygen radicals were tested: the non-permeant electron acceptor ferricyanide; the iron chelators desferrioxamine, desferrithiocin, octanohydroxamic acid, and pyridoxal isonicotinoyl hydrazone, which are thought to be capable of preventing the iron-catalyzed reduction of H2O2 to more reactive species; and the lipid-soluble free radical scavenger butylated hydroxyanisole. These compounds inhibited the proliferation of all potential responder cells in the MLC in a dose-dependent manner. Inhibition was observed only if these agents were present early (less than 40 hr) in the MLC; if added later, their effects were significantly reduced. In contrast, the interleukin 2 (IL 2)-dependent proliferation of CTLL-2 cells or Con A blasts was not affected by these compounds at concentrations that inhibited proliferation in MLC by greater than 90%. Interleukin 1 (IL 1) production by peritoneal exudate cells and IL 2 and IL 1 levels in MLC were not affected by any of the agents tested. By flow microfluorometry, the expression of IL 2 receptors on stimulated T cells was found to be inhibited in the presence of these drugs. Taken together, the data point to an important role for free radical-mediated processes during the early stages of T lymphocyte activation, before IL 2 receptor expression.
Interferon-gamma-activated human monocytes inhibit the intracellular multiplication of Legionella pneumophila.
Authors: Bhardwaj N , Nash T W , Horwitz M A 
Published: December 2022

Abstract
We have examined the interaction between interferon-gamma (IFN-gamma)-activated human monocytes and Legionella pneumophila, the agent of Legionnaires' disease. Human monocytes activated with human recombinant IFN-gamma inhibit the intracellular multiplication of L. pneumophila. The degree of inhibition is proportional to the concentration of IFN-gamma, and maximal inhibition consistently occurs with greater than or equal to 2 micrograms/ml. Monoclonal anti-IFN-gamma antibody completely neutralizes the capacity of IFN-gamma to activate monocytes. Monocytes infected 24 hr after explantation maximally inhibit L. pneumophila multiplication if treated with IFN-gamma before infection or up to 2 hr after infection; treatment 6 hr or more after infection results in submaximal inhibition. Monocytes infected 48 hr after explantation inhibit L. pneumophila multiplication maximally if treated with IFN-gamma up to 12 hr before infection, but submaximally if treated at the time of infection. Once activated, monocytes inhibit L. pneumophila multiplication in the absence of IFN-gamma in the culture. Strikingly, monocytes maximally inhibit L. pneumophila multiplication after treatment with IFN-gamma for as briefly as 1 hr before infection. In the absence of anti-L. pneumophila antibody, neither IFN-gamma-activated monocytes nor nonactivated monocytes kill L. pneumophila. In the presence of specific antibody and complement, IFN-gamma-activated monocytes kill a proportion (0.5 log) of an inoculum but not more than nonactivated monocytes. L. pneumophila forms a specialized phagosome in IFN-gamma-activated monocytes that does not differ ultrastructurally from the L. pneumophila phagosome in nonactivated monocytes. These results demonstrate that IFN-gamma can activate human monocytes to exert a potent antimicrobial effect against a highly virulent intracellular bacterial pathogen. These findings extend previous observations on interactions between activated mononuclear phagocytes and L. pneumophila, and additionally support the hypothesis that cell-mediated immunity plays a major role in host defense against L. pneumophila.
Antigen-specific Lyt-2+ cytolytic T lymphocytes from mice infected with the intracellular bacterium Listeria monocytogenes.
Authors: De Libero G , Kaufmann S H 
Published: December 2022

Abstract
In vitro expanded T cell lines were used to determine whether antigen-specific cytolytic T lymphocytes are generated after infection with the intracellular bacterium, Listeria monocytogenes. Spleen cells from infected mice were cultured in the presence of syngeneic accessory cells, listerial antigen, and interleukin 2 containing supernatants. Cell lines were greater than 98% Thy-1+, L3T4-, Lyt-2+. Bone-marrow macrophages were used as target cells in two in vitro cytolytic assay systems. The Lyt-2+ T cells killed bone marrow macrophages only when infected with L. monocytogenes as assessed in a 4-hr 51Cr release assay and in an 18-hr neutral red uptake assay. Cytolysis was blocked by anti-LFA-1 and anti-Lyt-2 monoclonal antibodies. These cytolytic T cells produced interferon-gamma after co-stimulation with antigen, accessory cells, and recombinant interleukin 2. Bone marrow macrophages infected with Mycobacterium bovis were not killed by T cells from L. monocytogenes-infected mice but by T cell lines from M. bovis-infected mice, indicating that cytolysis was antigen specific. L. monocytogenes-infected target cells of different haplotype were lysed by the Lyt-2+ T cells. By using a low cell density split culture system, antigen-specific, H-2-restricted cytolytic T cells could be identified. These findings demonstrate that during infection with intracellular bacteria, Lyt-2+ T cells with cytolytic activity are generated that may be involved in antibacterial protection.
Two distinct but overlapping antibody binding sites in the pre-S(2) region of HBsAg localized within 11 continuous residues.
Authors: Milich D R , McLachlan A , Chisari F V , Nakamura T , Thornton G B 
Published: December 2022

Abstract
The fine specificity of the humoral immune response to the pre-S(2) region of the hepatitis B surface antigen was studied. It was demonstrated that the murine antibody response to the pre-S(2) region is focused on residues 133 through 143, and two distinct but overlapping epitopes were identified within 11 continuous residues. One epitope, defined by p133-139, is group specific, and the other epitope, defined by p137-143, is influenced by a subtype-dependent amino acid substitution at residue 141. However, the influence of residue 141 was "covert" in that it was only detected when synthetic antigens of 19 amino acids or smaller were used as the solid-phase ligand. The minimum size of both epitopes (p133-139 and p137-143) was seven amino acids. The physical and chemical form of the immunogen (i.e., protein vs peptide; conjugated vs free peptide) influenced antibody fine specificity. In quantitative antibody inhibition studies it was demonstrated that antibodies with nonoverlapping as well as overlapping fine specificities were capable of mutual inhibition. Finally, human HBV-infected, patient sera were shown to possess anti-pre-S(2) region antibodies that recognized sequences in common with the murine antisera. These results have implications relevant to the design of synthetic and recombinant second generation HBV vaccines and diagnostic reagents.
Generation of tumor-specific transplantation antigens by UV radiation can occur independently of neoplastic transformation.
Authors: Hostetler L W , Ananthaswamy H N , Kripke M L 
Published: December 2022

Abstract
The purpose of this study was to determine whether the UV-associated antigens present on tumors induced in mice by chronic UV irradiation could be induced by in vitro irradiation of cells that were already tumorigenic, or whether their occurrence was associated with the primary neoplastic transformation event. Cells of a nonantigenic, spontaneous fibrosarcoma cell line were exposed to UV radiation in vitro, were cloned, and were tested for antigenic properties. A large number of the clones obtained after UV irradiation of the fibrosarcoma cells were highly antigenic (20 of 39), whereas clones derived from unirradiated cultures were not (0 of 10). The antigenic variants did not induce cross-protection among themselves, but induced only variant-specific immunity in vivo. Several antigenic variants were tested for susceptibility to the action of UV-induced suppressor cells, which seem to recognize a common determinant shared among UV-induced tumors. The variants tested were indeed subject to the activity of the UV-induced suppressor lymphocytes. These results demonstrate that the unique antigenic properties exhibited by UV-induced murine skin cancers are also exhibited by cells exposed to UV radiation in vitro. In addition, they imply that the UV-associated antigens arise as a consequence of exposing cells to UV radiation and that they can occur independently of an initial neoplastic transformation event.
Analysis of DR beta and DQ beta chain cDNA clones from a DR7 haplotype.
Authors: Karr R W , Gregersen P K , Obata F , Goldberg D , Maccari J , Alber C , Silver J 
Published: December 2022

Abstract
A cDNA library was constructed from a DR7, DRw53, DQw2 homozygous cell line, cDNA clones corresponding to DR beta and DQ beta chains were isolated, and the nucleotide sequences of the polymorphic first domains of these chains were determined. A novel screening strategy allowed rapid and simple identification of cDNA clones corresponding to both DR beta chains (DR7 beta1 and DR7 beta2): DR7 beta2 clones have a recognition site for the enzyme BssHII, whereas DR7 beta1 clones do not. The DR7 beta 1 sequence differs significantly from all previously described DR beta chains. As predicted by the presence of the BssHII site in DR7 beta 2 clones, the DR7 beta 2 sequence differs from the DR7 beta 1 sequence. The sequence of the DRw53-associated DR7 beta 2 chain is identical to the reported sequence of the DRw53-associated DR4 beta 2 chain. In addition, the sequence of the DQ beta chain from the DR7, DQw2 cell line is identical to the reported sequence of a DQ beta chain from a DR3, DQw2 cell. These findings raise interesting questions about the evolution of the DR3, DR4, and DR7 haplotypes.
Syngeneic monoclonal internal image anti-idiotopes as prophylactic vaccines.
Authors: Gaulton G N , Sharpe A H , Chang D W , Fields B N , Greene M I 
Published: December 2022

Abstract
A syngeneic monoclonal anti-idiotope that behaves as an internal image of the mammalian reovirus type 3 cellular attachment protein (viral hemagglutinin) was used in the syngeneic host for the induction of a prophylactic anti-viral antibody response. These studies were performed without the aid of co-stimulation by viral antigens. The high stringency of this system enables us to define the maximum constraints on the use of anti-idiotopes as anti-viral vaccines. We have used the murine BALB/c monoclonal IgM anti-idiotope 87.92.6 to study the idiotope and antigen specificity, kinetics, dose dependence, adjuvant, carrier, and valency requirements of anti-idiotope-induced anti-viral antibody responses. These studies show that the production of high titer neutralizing antibody requires a lengthy (60 day) immunization protocol, which includes the use of adjuvant and multivalent anti-idiotope, and is dependent on anti-idiotope concentrations of greater than 50 micrograms. When administered in this manner anti-idiotope can stimulate serotype-specific antibody responses across species barriers at levels comparable with those obtained after inoculation with virus. The practical efficacy of these reagents and procedures is documented by the ability of maternal immunization with anti-idiotope to confer complete protection in neonates from a potentially lethal reovirus type 3 viral infection.
Envelope proteins of human T cell leukemia virus type I: characterization by antisera to synthetic peptides and identification of a natural epitope.
Authors: Copeland T D , Tsai W P , Kim Y D , Oroszlan S 
Published: December 2022

Abstract
Three peptides corresponding to selected regions of the env gene products of human T cell leukemia virus type I were synthesized by solid-phase Merrifield techniques. The sequence of peptide designated SP-65 was identical to the predicted C-terminal 12 residues of the transmembrane protein p21env, and peptide SP-74 was inferred from a region shown to be highly conserved among mammalian retroviruses. The third peptide, SP-70, was derived from a C-terminal region of the surface glycoprotein gp46. Antibodies to each peptide were raised in rabbits and were used to identify and further characterize the proteins coded by the env gene. Despite being present at very low levels in purified viral preparations, these proteins were chromatographed by reverse-phase high pressure liquid chromatography and were located by Western blot analysis of the column fractions. Anti-SP-70 recognized the surface glycoprotein (gp46) and also its C-terminal cleavage fragment (gp16). Anti-SP-65 and anti-SP-74 both reacted with the hydrophobic transmembrane protein (p21) and provided evidence that this protein does not undergo apparent C-terminal processing during viral maturation, unlike the trans-membrane protein of murine leukemia virus. As expected, anti-SP-74 also reacted with homologous proteins from other Type C and Type D viruses, confirming that peptide SP-74 corresponds to a broadly conserved region of retroviral transmembrane proteins. SP-70, which is predicted to be quite near the C terminus of the major surface glycoprotein, was also reactive with sera of HTLV-I-positive patients, indicating that this peptide corresponds to, or is part of, a native epitope recognized by the natural host.
Evasion of the alternative complement pathway by metacyclic trypomastigotes of Trypanosoma cruzi: dependence on the developmentally regulated synthesis of surface protein and N-linked carbohydrate.
Authors: Sher A , Hieny S , Joiner K 
Published: December 2022

Abstract
Epimastigotes (EPI) of Trypanosoma cruzi are highly sensitive to lysis in fresh normal human serum by the alternative complement pathway (ACP). In contrast, metacyclic trypomastigotes (CMT) derived from EPI in stationary culture fail to activate the ACP and are thus resistant to serum-mediated lysis. To investigate the nature of the parasitic surface molecules which enable infective metacyclic trypomastigotes to evade the ACP, CMT were treated with a variety of different proteolytic and glycosidic enzymes, and their sensitivity to ACP-dependent lysis was tested. Pretreatment with pronase was found to cause a near complete reversal in the resistance of CMT to serum lysis, whereas trypsin or chymotrypsin induced smaller increases in complement sensitivity. Similarly, pretreatment with N-glycanase or neuraminidase also partially abrogated the resistance of CMT to ACP-dependent lysis. The effect of these enzymes on susceptibility to complement-mediated lysis was paralleled in increased C3 and C9 deposition on the organism. In addition, electrophoretic analysis of parasite-bound C3 indicated that the hemolytically inactive fragment, iC3b, was the major form of the molecule on CMT, while the hemolytically active fragment, C3b, predominated on pronase-treated CMT. Furthermore, when C3 was deposited on the parasite surface by means of purified ACP components, 80% of C3b on pronase-pretreated CMT but only 14% of the C3b on CMT bound the amplification protein factor B with high affinity, a prerequisite for efficient ACP activation. When cultured at 37 degrees C after pronase treatment, CMT gradually regained their resistance to ACP-mediated lysis. This process was blocked if puromycin, cycloheximide, or tunicamycin were included in the culture medium. The above findings suggest that evasion of the ACP by CMT is dependent on the developmentally regulated synthesis of protein as well as N-linked carbohydrate chains. A stage-specific 90,000 to 115,000 m.w. glycoprotein doublet present on the surface of CMT was shown to be uniquely sensitive to pronase digestion. Thus, this complex, which is also recognized by a CMT-specific monoclonal antibody, may be the glycoprotein component responsible for control of ACP activation
Heat-labile IgG2a antibodies affect cure of Trypanosoma musculi infection in C57BL/6 mice.
Authors: Wechsler D S , Kongshavn P A 
Published: December 2022

Abstract
Immune plasma (IP) obtained from mice cured of Trypanosoma musculi infection is able to mediate trypanosome clearance both in vivo and in vitro. A protein A-derived immunoglobulin fraction of IP containing primarily IgG2a and IgG3 shares this curative activity. Additional purification of IP with the use of anti-IgG2a and anti-IgG3 coupled to Sepharose beads demonstrates that the curative activity of IP resides solely in the IgG2a fraction; IP depleted of IgG2a is no longer able to effect T. musculi removal. Furthermore, this curative IgG2a is labile to heat treatment for 30 min at 56 degrees C. Enzyme-linked immunosorbent assays show that trypanosome-specific IgG2a builds up gradually over the course of infection, and temporarily drops slightly at the time of parasite clearance.
Different regulation of the L3T4-T cell subset by B cells in different mouse strains bearing the H-2k haplotype.
Authors: Brinkmann V , Sharma S D , Remington J S 
Published: December 2022

Abstract
Splenic L3T4-T cells from Toxoplasma gondii-infected CBA/J (H-2k, Igh 1a) but not C3H/He (H-2k, Igh 1j) mice responded with marked antigen-specific proliferation and interleukin 2 (IL 2) production, as well as concanavalin A-induced proliferation. The proliferative response of C3H/He spleen cells could be restored in part in vitro by addition of exogenous recombinant IL 2. The observed unresponsiveness of C3H/He spleen cells was due to the release of IL 2-inhibiting factors. These factors, present in culture supernatants from antigen restimulated C3H/He spleen cells, blocked the growth of an IL 2-dependent T cell line in the presence of optimal concentration of IL 2. During the early stages of infection, C3H/He splenic macrophages lacked the capacity to present antigen. In addition a nonspecific B cell-mediated suppression of T cell proliferation was observed. In later stages of infection macrophages displayed normal antigen-presenting function in comparison with macrophages of normal uninfected mice. At this stage of infection nonspecific, minor histocompatibility restricted B cell suppression was observed. These results suggest a possible role of B cells in regulation of T cell immunity to T. gondii.
Regulation of the immune response against UV-induced skin cancers: specificity of helper cells and their susceptibility to UV-induced suppressor cells.
Authors: Romerdahl C A , Kripke M L 
Published: December 2022

Abstract
The purpose of this study was to determine the role of T helper (Th) cells in the immune response to UV-induced tumors. Repeated exposure of mice to UV radiation results in the production of suppressor T lymphocytes that facilitate tumor growth by inhibiting host immunity. To investigate whether the suppressor T cells inhibit the response to UV tumors by blocking the generation of Th, we employed an indirect method for measuring helper cell activity. We found that Th were produced in normal mice after immunization with UV-induced tumors. These Th appeared to be specific for the immunizing tumors, in contrast to the UV-induced suppressor cells, which recognize UV-induced tumors as a group. The suppressor T cells responsible for inhibiting tumor rejection have no effect on tumor-specific helper cell activity in vitro. However, UV-induced suppressor T cells transferred into unirradiated mice seem to block the generation of helper cell activity after immunization with UV-produced tumors. These results suggest the UV-induced suppressor cells may prevent tumor rejection by blocking the generation of Th.
Stepwise immunologic selection of antigenic variants during tumor growth.
Authors: Urban J L , Kripke M L , Schreiber H 
Published: December 2022

Abstract
Using tumor-specific effector cells as probes, we have studied the immunologic changes that occur in tumor cells during continuous growth in a host. As a model, we used a highly immunogenic ultraviolet light (UV)-induced tumor that is rejected regularly by normal mice but grows progressively when transplanted into UV-irradiated mice. The immunogenic tumor growing continuously in these partially immunocompromised mice gave rise to genetically stable progressor variants that were poorly immunogenic. A sequence of changes in susceptibility to activated macrophages and tumor-specific cytolytic T cells was observed when serial reisolates from the continuously growing tumors were analyzed. First, the tumor cells developed resistance to the cytocidal effects of activated macrophages. This was followed by the loss of one and then a second tumor-specific antigen defined by syngeneic cytolytic T cells. The phenotypes of the developing antigen loss variants and their sequence of appearance were the same in several independent experiments, and the process was apparently determined by a hierarchy of the host's immune response to multiple independent tumor-specific antigens expressed by a single malignant cell. Our ability to generate the predicted variants in vitro before they actually appear in vivo suggests a possible approach to preventing the outgrowth of such immunoselected variants from a tumor.
A monoclonal antibody to a cross-reactive idiotype on cationic human anti-DNA antibodies expressing lambda light chains: a new reagent to identify a potentially differential pathogenic subset.
Authors: Livneh A , Halpern A , Perkins D , Lazo A , Halpern R , Diamond B 
Published: December 2022

Abstract
Anti-double-stranded DNA antibodies are commonly found in the serum of patients with systemic lupus erythematosus (SLE). They are a heterogeneous group of antibodies thought to differ in pathogenicity. The degree of heterogeneity and the structural correlates of pathogenicity, however, remain poorly defined. To address these questions we have been generating anti-idiotypic antibodies to the anti-DNA antibodies found in the serum of SLE patients. In this paper we report the generation and characterization of a new murine monoclonal anti-idiotype, 8.12, that recognizes a subset of anti-DNA antibodies that is present in serum of approximately 50% of patients with SLE. The 8.12 anti-idiotype recognizes uniquely cationic anti-DNA antibodies, all of which express lambda light chains. In murine models of SLE, it has been suggested that cationic anti-DNA antibodies are preferentially deposited in the kidney. It may be, therefore, that 8.12 recognizes a subset of anti-DNA antibodies of particular pathogenic significance.