bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complement-mediated serum cytotoxicity for Leishmania major amastigotes: killing by serum deficient in early components of the membrane attack complex.
Authors: Hoover D L , Berger M , Hammer C H , Meltzer M S 
Published: January 2023

Abstract
Leishmania major, the agent of Oriental sore, is an obligate intracellular parasite of macrophages in mammalian hosts. Man's immune defense against this organism requires participation of specifically sensitized lymphocytes and activated macrophages. Recent studies, however, have demonstrated that as little as 1/120 concentration of normal human serum is highly cytotoxic for the amastigote form of L. major. Initiation of the lethal process occurs rapidly, requiring only 30 sec of parasite exposure to serum, and is mediated by antibody-independent activation of the alternate complement pathway. The molecular mechanism of cytotoxicity is not known, but may require participation of the membrane attack complex, C5b-9. We investigated this possibility by treating amastigotes with human sera genetically deficient in complement components C5, 6, 7, 8, or 9. We then measured viability of treated parasites by amastigote-promastigote conversion. Our results were quite unexpected: not only did C9-deficient serum kill organisms, but sera singly deficient in each of the preceding components C6 to C8 were also cytotoxic. The degree of cytotoxicity was related both to serum concentration and to the point in the complement cascade at which deficiency occurred. Sera lacking C6 or C7 were less cytotoxic than those deficient in C8, which were less toxic than those deficient in C9. Cytoxicity of deficient sera was abolished by heating serum to 56 degrees C for 30 min. These findings indicate that an incomplete membrane attack complex may mediate cytotoxicity for L. major amastigotes. Moreover, our results raise important questions regarding the mechanism by which the complex is assembled on the surface of a living, unicellular eukaryotic organism.
Induction of protective immune response in cats by vaccination with feline leukemia virus iscom.
Authors: Osterhaus A , Weijer K , Uytdehaag F , Jarrett O , Sundquist B , Morein B 
Published: January 2023

Abstract
An effective candidate subunit vaccine consisting of the gp 70/85 of feline leukemia virus (FeLV) was prepared by using the immunostimulating complex (iscom) method for the presentation of membrane proteins of enveloped viruses. Two 32-wk-old specific pathogen-free (SPF) cats were immunized with a FeLV iscom vaccine prepared from the supernatant fluid of the FL74 tumor cell line without adjuvant. Both cats developed FeLV serum antibodies, as measured in an enzyme-linked immunosorbent assay (ELISA) and in a virus neutralization test. A proportion of the antibodies were directed to an epitope located on gp70/85, which was shown in competition ELISA with a peroxidase-labeled virus-neutralizing monoclonal antibody to be shared by all three subtypes of FeLV. The protective effect of FeLV iscom was studied by vaccinating six 8-wk-old SPF cats with iscom prepared from cell culture supernatant of another tumor cell line F422, followed by oronasal challenge with 10(6) ffu FeLV-A (strain Glasgow-1). Six unvaccinated cats were also challenged with the same dose of FeLV. The vaccinated cats developed FeLV serum antibodies, some of which were directed to the shared epitope on gp70/85. At 10 wk after challenge, none was viremic, whereas three of the control cats had developed FeLV viremia. The potential of FeLV iscom as a vaccine against FeLV-associated disease in cats, and of iscom vaccines for protection against mammalian retrovirus infections, is discussed.
Induction of tumor-inhibitory macrophages with a novel synthetic immunomodulator, 3,6-bis(2-piperidinoethoxy)acridine trihydrochloride (CL 246,738).
Authors: Wang B S , Lumanglas A L , Ruszala-Mallon V M , Durr F E 
Published: January 2023

Abstract
3,6-bis(2-piperidinoethoxy)acridine trihydrochloride (CL 246,738) has been investigated for its immunomodulatory effect on murine macrophages. Incubation of macrophages harvested from the peritoneal cavities of normal mice with the compound for 48 to 72 hr rendered these cells inhibitory to the growth of tumor cells in vitro. Activation of tumor-inhibitory macrophages occurred over a range of concentrations (0.025 to 0.1 micrograms/ml) producing no direct inhibitory effects on tumor cells. Treatment of effector cells with carrageenan abrogated the effect, whereas treatment with anti-Thy-1.2 antibody and C did not, suggesting that the primary effectors were macrophages rather than T lymphocytes. These activated macrophages also manifested in vitro tumor cytolysis. In vivo studies indicated that peritoneal macrophages from mice treated with single oral doses of 100 to 400 mg/kg of the compound were also inhibitory to tumor cell growth in vitro. Effector macrophages became demonstrable in mice as early as 1 day after drug administration, reached peak activity at day 12, and disappeared by day 31, indicating a rapid onset but long-persisting effect. The tumor cytostatic activity of these macrophages was augmented by endotoxin at the dose of endotoxin that, in itself, had no effect. The addition of protease inhibitors, N-alpha-p-tosyl-L-lysine chloromethyl ketone and aprotinin, to cultures markedly diminished the cytostatic effect, suggesting that the release of neutral protease(s) could account for the inhibitory effects of the macrophages. On the other hand, hydrogen peroxide and arginase seemed excluded as the mechanism of action because the effect was not sensitive to treatment with catalase and exogenous arginine. The present findings indicate that CL 246,738 is an orally active immunopotentiator capable of inducing tumor-inhibitory macrophages both in vitro and in vivo.
Synergistic activation by recombinant mouse interferon-gamma and muramyl dipeptide of tumoricidal properties in mouse macrophages.
Authors: Saiki I , Fidler I J 
Published: January 2023

Abstract
Mouse peritoneal macrophages were activated to become cytotoxic against B16-BL6 melanoma cells by the combination of subthreshold amounts of murine interferon-gamma (IFN-gamma; 0.1 to 10 U/ml) and N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP; 0.001 to 10 micrograms/ml), but not by the combination of pH 2-treated IFN-gamma and MDP, heat-treated IFN-gamma and MDP, or IFN-gamma and the inactive stereoisomer of MDP, N-acetyl-muramyl-D-alanyl-D-isoglutamine (MDP-D). The encapsulation of intact IFN-gamma and MDP within the same liposome preparation was synergistic for macrophage activation. In contrast, the presentation of identical concentrations of IFN-gamma and MDP in separate liposome preparations did not activate macrophages. These data allow us to conclude that the encapsulation of genetically engineered IFN-gamma and synthetically produced MDP within the same liposome is highly efficient in producing synergistic activation of tumoricidal properties in mouse macrophages.
Identification of a structure on human melanoma cells recognized by CTL exhibiting anomalous killer cell function.
Authors: Werkmeister J A , Triglia T , Andrews P , Burns G F 
Published: January 2023

Abstract
The structures involved in the recognition of melanoma cells by nonspecific cytotoxic T lymphocytes (CTL) activated in mixed lymphocyte culture were investigated with monoclonal antibodies (MAb) which blocked this anomalous killer (AK) function. Of over 2000 MAb raised against melanoma cells, only three inhibited killing; one of these, an IgMk termed Leo Me13, was investigated in detail. In antibody-binding studies using a large range of cultured tumor cells, it was shown that Leo Me13 was relatively specific for melanoma cells. Of more importance, Leo Me13 inhibited conjugate formation between AK cells and melanoma target cells by 60 to 80% and caused an eight- to 10-fold reduction in killing. The MAb did not immunoprecipitate protein from melanoma cells surface-labeled with 125I, and thin-layer chromatography followed by immunoblotting of the separated glycolipids from melanoma cells indicated that the epitope was on acidic glycolipids migrating between GM1 and GD1a; moreover, treatment of melanoma cells with neuraminidase resulted in complete loss of binding of Leo Me13 but not of other anti-melanoma antibodies which did not inhibit AK cell-mediated lysis. Other melanoma-reactive MAb of the same isotype as Leo Me13 did not block killing of melanoma cells, but one documented antibody, R24, an IgG3 with specificity for the ganglioside GD3, was found to inhibit this function. These data suggest that the AK cells recognize and bind to melanoma cells by a secondary "lectin-type" receptor for a carbohydrate moiety.
Monoclonal antibodies against an H-2Kb-specific cytotoxic T cell clone detect several clone-specific molecules.
Authors: Hua C , Boyer C , Buferne M , Schmitt-Verhulst A M 
Published: January 2023

Abstract
Monoclonal antibodies (mAb) were prepared from the spleen of a BALB.K mouse immunized with a H-2Kb-specific alloreactive cytolytic T cell (CTL) clone of B10.BR origin, KB5-C20. Six of these mAb were selected for specific binding to the immunizing clone. Only one of these mAb, Désiré-1, inhibited the CTL activity of clone KB5-C20. Functional and biochemical evidence showed mAb Désiré-1 to be anti-clonotypic (anti-Ti). This mAb immunoprecipitated from lysates of clone KB5-C20 a protein that migrated at 80 KD in nonreducing conditions and at 40 to 45 KD in reducing conditions. Analysis in NEPHGE resolved the latter into an acidic chain of 43 KD and a basic chain of 40 KD. An additional protein was coprecipitated at 25 KD in nonreducing and 27 KD in reducing conditions, which was distinct from the Thy-1 antigen. Expression of the clonotype defined by Désiré-1 was found on clone KB5-C20 and on clone KB5-A7 originating from the same B10.BR T cell population. These two clones exhibited a similar pattern of reactivity on H-2Kbm mutant target cells. Another clone (KB5-C1) from the same B10.BR T population showed a distinct reactivity pattern on the H-2Kbm mutant target cells and did not express the Désiré-1 clonotype, nor did Con A-activated B10.BR blast cells or H-2Kb-specific clone BM3.3 of CBA/J origin. Among the five other selected mAb, one reacted with the three Kb-specific CTL clones of B10.BR, but not with the Kb-specific clone of CBA origin, whereas the last four mAb bound only to clone KB5-C20. None of these mAb could immunoprecipitate the Ti alpha/beta chains. Ti modulation induced by mAb Désiré-1 on clone KB5-C20 did not induce comodulation of the structures bound by the other five mAb on clone KB5-C20, thus indicating that these structures were not part of the Ti-T3 complex. These results characterize a clonotypic mAb reacting with an H-2Kb-specific CTL clone that will be useful in future studies. They also indicate that screening for clone-specific mAb by selective binding assays may select for mAb against as yet undefined structures, some of which exhibit an apparently clone-specific distribution.
Study of idiotopic suppression induced by anti-cross-reactive idiotype monoclonal antibody in the anti-p-azophenylarsonate antibody response.
Authors: Hiernaux J R , Marvel J , Meyers P , Moser M , Leo O , Slaoui M , Urbain J 
Published: January 2023

Abstract
A/J mice immunized with p-azophenylarsonate coupled to keyhole limpet hemocyanin produce antibodies expressing a cross-reactive idiotype (CRIA). The pretreatment of A/J mice with anti-idiotypic polyclonal or monoclonal antibody directed against the major cross-reactive idiotype (CRIA) borne by p-azophenylarsonate-specific antibody can lead to idiotypic suppression. In this study, we investigate this idiotypic suppression by using four mAb2 (E4, H8, E3, 2D3) recognizing distinct idiotopes whose expression is related to the presence of particular gene segments of the heavy chain V region. 2D3 expression has been related to the presence of some amino acid in the CDR2 region of the VH gene segment derived from the germ line VH IdCR11. So far, the latter is the only germ-line gene coding for CRIA+ antibody that has been identified in the A/J genome. E4 and H8 expression has been related to the use of a particular D segment, whereas E3 expression has been attributed to certain combinations of D and JH segments. Therefore, we might expect independent regulation of the expression of those various idiotopes in relation to the mechanism of gene recombination. Indeed, we observed that 2D3-suppressed A/J mice still produce the three other idiotopes, suggesting the recombination of those particular D and J segments with a different VH gene. Such a gene has been identified in the genome of BALB/c mice. A/J mice pretreated with one of the other three mAb2 are generally cosuppressed for the expression of E4, H8, and E3, but they still produce 2D3+ antibody. In this case, the IdCR11 VH germ-line gene is most probably recombined with different D and J segments. Molecular evidence for the existence of such molecules has also been presented in the literature. So our serologic data on idiotopic suppression in the arsonate system can be compared with recent data provided by molecular genetics.
Induction of suppression by a murine nonspecific suppressor-inducer cell line (M1-A5). II. The role of prostaglandins.
Authors: Almawi W Y , Pope B L 
Published: January 2023

Abstract
A murine nonspecific suppressor-inducer cell line (M1-A5) was generated from the spleen cells of a mouse bearing an advanced methylcholanthrene-induced fibrosarcoma. We previously demonstrated the capability of M1-A5 cells to activate suppressor cells from the spleen cells of unprimed mice. We demonstrate here that induction of suppression by M1-A5 cells was blocked by acetylsalicylic acid (ASA) and ibuprofen at concentrations which block prostaglandin (PG) synthesis. Maximal blockade of the induction of suppression by M1-A5 cells was seen when ASA was added at the initiation of culture, and it required inhibition of PG synthesis at the level of the inducer (M1-A5 cells) population. However, ASA blockade of suppressor cell activation by M1-A5 cells was not due to ASA acetylating suppressor-inducing factor. Exogenously added PGE1, PGE2, and PGI2, but not PGF2 alpha or PGD2, were able to restore the inducing capability of M1-A5 cells, which had been blocked by ASA. However, PGE1, PGE2, or PGI2 did not reconstitute an inactive suppressor-inducing factor. These results suggest that PG act to modulate the release of suppressor-inducing factor from M1-A5 cells.
Inhibition of immune opsonin-independent phagocytosis by antibody to a pulmonary macrophage cell surface antigen.
Authors: Parod R J , Godleski J J , Brain J D 
Published: January 2023

Abstract
Unlike other hamster phagocytes, hamster pulmonary macrophages (PM) avidly ingest albumin-coated latex particles in the absence of serum. They also possess a highly specific cell surface antigen. To evaluate the relationship between these two characteristics, PM were incubated with mouse monoclonal antibody directed against the PM antigen. After unbound antibody was removed, the amount of bound antibody and the phagocytic capability of PM were measured by flow cytometry and fluorescence microscopy. Maximum antibody binding produced a 25% inhibition of ingestion. Particle attachment was not affected. This effect was antigen specific, since neither a nonspecific mouse myeloma protein of the same subclass nor a mouse antibody that bound to another hamster surface antigen had any effect on binding or ingestion. If antigen-specific F(ab')2 fragments were introduced both before and during the period of phagocytosis, the inhibition of particle ingestion approached 100%. Particle binding increased at low F(ab')2 concentrations but declined at higher concentrations. Because calcium may play a role in the ingestion process, the effect of antibody on 45Ca uptake was evaluated. It was observed that antigen-specific F(ab')2 fragments stimulated 45Ca uptake, whereas control antibodies did not. These results suggest that the antigen reacting with our anti-hamster PM monoclonal antibody is involved in immune opsonin-independent phagocytosis and that calcium participates in this phagocytic process.
Monoclonal antibodies that inhibit activation and proliferation of lymphocytes. II. Requisite role of the monoclonal antibody-defined antigen systems in activation and proliferation of human and rat lymphocytes.
Authors: Yagita H , Hashimoto Y 
Published: January 2023

Abstract
A murine monoclonal antibody (MoAb) B3 to rat cells and MoAb HBJ127 and HBJ98 to human cells were found previously to recognize the homologous antigen systems (gp130 in the rat and gp125 in the human) which are predominantly distributed on the cell surface of proliferating cells of the respective species, and the expression of the antigen systems in lymphocytes were indicated previously to correlate closely with the activation and proliferation of the lymphocytes. In this respect, the in vitro effects of these MoAb on the nucleic acid synthesis, cell cycles, or proliferation of stimulated rat and human lymphocytes were examined by use of T cell-enriched and B cell-enriched cell populations. The addition of B3 MoAb to cultures diminished Con A-induced or allogeneic mixed lymphocyte culture-induced rat T cell proliferation and lipopolysaccharide-induced rat B cell proliferation, whereas B31 MoAb, which is unreactive with the gp130 antigen, did not inhibit these lymphocyte responses. Similarly, both HBJ127 and HBJ98 MoAb could inhibit the human lymphocyte proliferation in vitro, although HBJ127 MoAb showed about eight times greater inhibitory activity than did HBJ98 MoAb; HBJ127 MoAb almost completely inhibited the DNA synthesis of the Con A-stimulated lymphocytes at concentrations higher than 13 micrograms/ml. The flow cytometric analysis of the cellular nucleic acid contents with acridine orange-stained cells showed that when B3 MoAb and Con A were simultaneously added to unstimulated rat T cells, progression of the cell cycle was blocked at the G0 to G1 transition. In this culture condition, the appearance of the B3-defined antigen was arrested in a moderate level, as determined with fluorescein-stained cells. On the addition of B3 MoAb to the culture of the T cells after 24-hr Con A stimulation, the MoAb also strongly inhibited the cellular DNA synthesis, but it did not arrest the cell cycle at a certain phase and did not modulate the corresponding antigen. These data suggest that the B3 MoAb-defined antigen on the rat lymphocytes and the HBJ127/HBJ98 MoAb-defined antigen on the human lymphocytes may play some requisite roles not only in lymphocyte activation but also in the subsequent progression through the cell cycle to proliferate.
T cell activation of antigen-specific antibody responses by large B cells is MHC restricted.
Authors: Mosier D E 
Published: January 2023

Abstract
The activation of small, resting B cells for antibody synthesis by helper T cells has been proposed to require an MHC-restricted interaction between the T and B cells. Large, activated B lymphocytes were, in contrast, thought to be activated by an unrestricted pathway. We re-examined this issue and found that both large and small size fractionated murine B lymphocytes required an MHC-restricted interaction with helper T cells to be activated for specific antibody synthesis. Polyspecific antibody synthesis in the same cultures was not dependent upon an MHC-restricted T-B interaction for any size category of B cell. These results are interpreted as reflecting the ability of antigen-specific B cells to focus and present antigen to T cells, in contrast to B cells of random specificity, which have no effective focusing mechanism for a given experimental antigen. We found that the polyspecific response required much higher antigen concentrations than the antigen-specific response, a result consistent with the antigen-focusing hypothesis.
Antigen-specific functions of a CD4+ subset of human T lymphocytes with granular morphology.
Authors: Morishita Y , Martin P J , Bean M A , Yamada H , Hansen J A 
Published: January 2023

Abstract
We previously showed that a small proportion of the CD4+ human lymphocytes express the C3bi receptor (CD11). In the present investigation these cells were found to have the homogeneous morphology of granular lymphocytes. Between 70 and 80% of the cells reacted with antibody Leu-7, but they did not express Fc receptors and had no spontaneous cytotoxic activity against the NK-sensitive cell line K562. The CD11+/CD4+ cells uniformly expressed CD3 and could be induced to express IL 2 receptors by activation with PHA or anti-CD3 antibody. Compared with unfractionated T cells, however, CD11+/CD4+ granular lymphocytes had a reduced ability to produce IL 2 after stimulation with PHA or anti-CD3 antibody. Nevertheless, the CD11+/CD4+ subset generated specific allocytotoxicity after stimulation with allogeneic cells and culture in IL 2. Furthermore, the CD11+/CD4+ cells also proliferated after stimulation with tetanus toxoid and PPD. Thus some cells of the CD11+/CD4+ subset are capable of antigen-specific responses. These results indicate that certain CD11+ cells with granular morphology are mature T lymphocytes.
The role of the immune response in TMEV infection and the development of late onset demyelination.
Authors: Rauch H C , Montgomery I N 
Published: January 2023

Abstract
The nature of the role of the immune response to TMEV in the development of LODD after TMEV infection was examined by different means. Immunosuppression by both cyclophosphamide (postinfection) or adult thymectomy and ATS treatment (preinfection) did not inhibit clinical LODD. Adoptive transfer of spleen cells from infected donors with LODD facilitates LODD in the recipients compared with i.v. transfer of the freeze-thaw supernatants from such suspensions (although virus is present in splenocyte suspensions). The immune response to TMEV, both lymphoproliferative and antibody, reaches a peak coincidental with the development of LODD. The role of the immune response is equivocal depending on the stage of the viral infection, the timing of immunosuppressive treatment, and assessment.
Membrane-associated IL 1-like activity on rat dendritic cells.
Authors: Nagelkerken L M , van Breda Vriesman P J 
Published: January 2023

Abstract
The secretion of interleukin 1 (IL 1) by rat dendritic cells (DC) was studied in relation to their ability to induce the production of interleukin 2 (IL 2) and to induce IL 2 responsiveness. IL 1 (or IL 1-like activity) was measured by its capacity to enhance IL 2 production by EL4 cells. In contrast to peritoneal exudate cells (PEC) or splenic adherent cells, DC from thoracic duct lymph (TD-DC) or from spleen did not secrete detectable amounts of IL 1 on stimulation with LPS/Silica. However, TD-DC and splenic DC were able to enhance IL 2 production by EL4 cells directly, and were only two times less effective than PEC. By preventing cell-to-cell contact between stimulator cells and EL4 cells, it was demonstrated that most of the IL 2-inducing activity of TD-DC and PEC was associated with the cell membrane. Treatment with 1% paraformaldehyde (PFA) to abolish metabolic activity resulted in a 50% decrease (or inactivation) of IL 2-inducing activity of TD-DC in the EL4 assay. Moreover, UVB-irradiation (300 mJ/cm2) of TD-DC, which has been described to inhibit the release of IL 1 by macrophages, caused a 70% decrease in IL 2-inducing activity. In a primary allogeneic mixed leukocyte reaction, neither PFA-treated TD-DC nor UV-irradiated TD-DC were able to induce T cell proliferation or IL 2 production. The cells were, however, able to induce IL 2 responsiveness, i.e., T cell proliferation in the presence of excess human recombinant IL 2. The finding that IL 1 enhanced T cell responses to PFA-treated or UV-irradiated TD-DC in the absence and in the presence of excess IL 2 indicates that loss of stimulatory activity of TD-DC may be due in part to loss or inactivation of IL 1. These results suggest that membrane-associated structures, that are identical to or mimic IL 1, are involved in the activation of T cells by DC.