bluuebunny/crossref_metadata_2025_split huggingface dataset:
C3d-K, a kallikrein cleavage fragment of iC3b is a potent inhibitor of cellular proliferation.
Authors: Thoman M L , Meuth J L , Morgan E L , Weigle W O , Hugli T E 
Published: December 2022

Abstract
The C3d-K fragment generated from human iC3b by plasma kallikrein is a potent suppressant of cellular proliferation. Originally characterized as inhibiting human and murine T lymphocyte function, C3d-K is shown in these studies to suppress mitogen-induced B cell growth, the spontaneous proliferation of several tumor cell lines, as well as all forms of T cell proliferation, including that induced by interleukin 2 (IL 2). In addition, synthesis of IL 2 in mixed lymphocyte cultures is blocked by C3d-K, but not IL 2 synthesis induced by Con A. The C3d-K fragment has no effect on resting cells; however, sensitivity to the inhibitory effect of C3d-K is acquired during the activation process. Because the proliferation of mitogen-activated spleen cells is not inhibited by exposure to C3d-K for the initial 24 hr of culture, only late steps in the cell activation process are C3d-K sensitive. When C3d-K is present throughout the course of the 72-hr culture, suppression was observed. Data obtained with the tumor cell lines suggest that once suppression is achieved, it is long-lasting even in the absence of C3d-K.
Properties of prostaglandin-sensitive adenylate cyclase system of a murine macrophage-like cell line (P388D1).
Authors: Fernandez-Botran R , Suzuki T 
Published: December 2022

Abstract
The properties of basal and prostaglandin (PG)-stimulated adenylate cyclase of membrane preparations of P388D1 cells were investigated. Three partially purified membrane fractions were obtained by sucrose density gradient centrifugation at the final step of purification from crude homogenate. About 96% of the basal and 89% of PGE2-stimulated adenylate cyclase activity in the homogenate were recovered in three membrane fractions. Two lighter membrane fractions (I and II), which were enriched 11-fold and 8.4-fold in adenylate cyclase activity over crude homogenate, were pooled and subjected to various studies. Results suggested that the basal activity of the membrane preparations has, as in many other cell types, a relatively broad pH optimum (pH 7.5 to 8.5), requires Mg2+, which must be present in excess ATP, and is inhibited by Ca2+. Highly reactive sulfhydryl group(s), which may be present in the lipid bilayer, is required for the adenylate cyclase activity. Because both fluoride ions and GTP augment the enzymatic activity, P388D1 cell membrane adenylate cyclase must possess stimulatory guanine nucleotide-binding protein. The membrane preparations respond to exogeneously added PG by 1.5-fold to 3-fold increase in adenosine 3'-5' cyclic monophosphate (cAMP) production. The magnitude of PG-responsiveness was dependent on the types of PG and the order of potency in stimulation was PGE1 greater than PGE2 greater than PGI2. PGA1, B1, B2, F1 alpha, and F2 alpha stimulated adenylate cyclase only at the highest concentration tested.
Melittin-specific monoclonal and polyclonal IgE and IgG1 antibodies from mice.
Authors: King T P , Kochoumian L , Joslyn A 
Published: December 2022

Abstract
Melittin, a bee venom peptide consisting of 26 amino acid residues, elicited high IgG and IgE antibody responses in mice of BALB/c and CAF1 strains, but not in mice of A/J, AKR, and C57BL/6 strains. Greater than 80% of the melittin-specific antibodies in sera of responder mice were found to bind the hydrophilic carboxyl-terminal heptapeptide of melittin. Three melittin-specific monoclonal antibodies were obtained from responder mice by the hybridoma technique. Two are of the IgG1 isotype and one is of the IgE isotype. One monoclonal antibody of the IgG1 isotype binds the carboxyl-terminal heptapeptide of melittin, while the other two monoclonal antibodies do not. However, competitive binding studies suggest that all three monoclonal Ig bind at the same, or adjacent, site of melittin. These findings, together with the known amphiphilic property of melittin, suggest that the immunogenicity of this peptide is a consequence of its binding to cell surface phospholipids.
Humoral immunity in experimental syphilis: the demonstration of IgG as a treponemicidal factor in immune rabbit serum.
Authors: Blanco D R , Miller J N , Hanff P A 
Published: December 2022

Abstract
The neutralizing activity present in immune rabbit serum (IRS) against virulent Treponema pallidum was shown to be mediated by IgG and complement. IgG was isolated and purified from both IRS and nonimmune rabbit serum (NRS) by the use of an affinity system in which staphylococcal protein A was conjugated to Sepharose 4B. The purity of the isolated IgG fractions was demonstrated by both immunoelectrophoresis and SDS-polyacrylamide gel electrophoresis. Fractions of IgG were tested for specific neutralizing activity as measured by an in vitro-in vivo neutralization test. Lesions failed to develop at 80% of the sites inoculated with treponemal suspensions containing IgG from IRS in the presence of unheated NRS as a source of complement; delayed atypical lesions were observed at the remaining sites. In contrast, typical lesions developed at all sites inoculated with suspensions containing IgG from IRS in the presence of heated NRS. They were significantly delayed, however, as compared with lesion development at control sites inoculated with suspensions containing IgG from NRS. These results provide the first direct evidence for an IgG complement-mediated treponemicidal mechanism operative in immune serum from rabbits with latent syphilis.
Modulation of macrophage activation and resistance by suppressor T lymphocytes in chronic murine Schistosoma mansoni infection.
Authors: Olds G R , Ellner J J 
Published: December 2022

Abstract
Activated macrophages (M phi) appear responsible for at least part of the concomitant resistance in mice infected with Schistosoma mansoni. We found that as murine S. mansoni progressed from acute (8 to 12 wk of infection) to chronic (16 to 24 wk) stages, acquired resistance decreased (57% resistance to challenge with cercariae at 8 wk vs 28% by 24 wk, p less than 0.05), as did macrophage activation (21% +/- 2 killing of schistosomula by 8 wk M phi vs 8% +/- 2 for 24 wk M phi, p less than 0.01). T cells from the spleens of 8 wk-infected mice were capable of activating M phi from naive animals when stimulated with worm antigens (24% +/- 2 killing vs 8% +/- 2 induced by normal T cells, p less than 0.01); T cells obtained from 24 wk-infected mice did not activate M phi (13% +/- 2 killing). Furthermore, T cells from 24 wk-infected animals suppressed activation of M phi by 8 wk T cells. The addition of 10(5) 24 wk T cells to 3 X 10(5) antigen-stimulated 8 wk T cells reduced subsequent M phi killing from 27% +/- 4 to 13% +/- 2 (p less than 0.05). Week 24 T cells (3 X 10(5] reduced this additionally to 9% +/- 1 (p less than 0.01), a value no greater than that of unstimulated M phi. The subpopulation of T cells responsible for suppression of M phi activation was Lyt-2+1- nonadherent T cells. Cyclophosphamide treatment of chronically infected mice resulted in enhanced resistance (41%), M phi activation (18% +/- 1 killing), and T cell activation of naive M phi (10% +/- 1 killing). Thus, during chronic S. mansoni infection, resistance to reinfection wanes in parallel to and perhaps because of development of suppressor T cells that interfere with T-dependent M phi activation.
Immunotherapy of lymphoid and nonlymphoid tumors with monoclonal anti-Lyt-1 antibodies.
Authors: Hollander N 
Published: December 2022

Abstract
Monoclonal antibodies against the T cell differentiation antigen Lyt-1 were effective in the therapy of transplanted mouse tumors. A possible mechanism whereby anti-Lyt-1 antibodies directly bind and affect the tumor cells was excluded by the following findings: a) growth of lymphoid and nonlymphoid tumors (which lack Lyt-1 antigen) was affected by anti-Lyt-1 antibodies; and b) the curative effect of passively administered anti-Lyt-1 anti-bodies was abrogated in mice depleted of T cells, supporting a mechanism whereby host Lyt-1+ cells were involved in tumor therapy. Treatment with anti-Lyt-1 antibodies was not accompanied by depletion of Lyt-1+ cells from lymphoid organs, indicating that the administered antibodies altered Lyt-1+ cell functions without affecting their frequency. In view of the in vitro enhancing effects of anti-Lyt-1 antibodies on a variety of immune responses (including lymphokine secretion and generation of cytotoxic T cell), it is suggested that the potentiation of Lyt-1+ cell activity by passively administered anti-Lyt-1 antibodies results in tumor rejection.
B cell activation. VI. Effects of exogenous diglyceride and modulators of phospholipid metabolism suggest a central role for diacylglycerol generation in transmembrane signaling by mIg.
Authors: Coggeshall K M , Cambier J C 
Published: December 2022

Abstract
Previous evidence indicates that in vitro activators of protein kinase C, such as phorbol myristate acetate (PMA), are able to induce early activation events in murine B cells, including membrane depolarization and increased I-A antigen expression. These same events are induced by specific antigen and anti-receptor antibody. This evidence suggests that protein kinase C activation may be an important intermediary event in mIg-mediated transmembrane signaling. Previously, investigators have suggested that protein kinase C activation is regulated by a novel second messenger, diacylglycerol (DG), and DG is generated by phosphatidylinositol (PI) hydrolysis after receptor-ligand interaction in many systems. In view of this concept, we examined the effects of nonspecific activators and inhibitors of DG production and DG itself on membrane potential and levels of I-A antigen expression in murine B cells. Our results indicate that exposure to DG, or induction of DG production by treatment of B cells with exogenous phospholipase C, results in depolarization and increased I-A antigen expression similar to that induced by anti-receptor antibody and specific antigen. Furthermore, we demonstrate that depolarization and increased I-A expression induced by anti-receptor antibody is blocked under conditions in which DG production is inhibited. As expected, based on its direct activation of protein kinase C, PMA stimulation is unaffected by this inhibition. These results support our earlier hypothesis that occupancy of antigen receptors on B cells is linked to subsequent activation events by PI hydrolysis, DG generation, and protein kinase C activation.
In vivo administration of purified human interleukin 2. I. Half-life and immunologic effects of the Jurkat cell line-derived interleukin 2.
Authors: Lotze M T , Frana L W , Sharrow S O , Robb R J , Rosenberg S A 
Published: December 2022

Abstract
A total of 12 patients with cancer or the acquired immunodeficiency syndrome have been treated with Jurkat-derived purified human interleukin 2 (IL 2). The toxicity was dose-related and consisted primarily of fever, chills, malaise, and mild reversible hepatic dysfunction. No evidence of clinical efficacy was seen when IL 2 was administered at doses of up to 2000 micrograms by bolus or continuous infusion once a week for 4 wk. No significant chronic immunologic effects (changes in mitogen responsiveness of induction of cytotoxic cells) were demonstrated. IL 2 was measured in the serum of patients, and a half-life of approximately 5 to 7 min was demonstrated with a second component of clearance of 30 to 120 min. Heating the serum at 56 degrees C for 30 min allowed for detection of smaller quantities of IL 2 by removing a serum inhibitor whose effect was seen at dilutions of up to 1/80 in our biologic assay. Sustained levels of IL 2 could be maintained by continuous infusion. Acute effects of IL 2 administration included a rapid decrease in peripheral mononuclear cells with a shift to cells of macrophage lineage and a rapid decrease in total T lymphocytes and T lymphocyte subsets. IL 2 responsiveness of peripheral mononuclear cells decreased within 15 min of IL 2 administration, with a concurrent decrease in the ability to generate lymphokine-activated killer cells. These changes did not recover until 48 hr after IL 2 administration. A rise in serum ACTH and cortisol levels was seen after the administration of 1 to 2 mg of IL 2. Future studies will evaluate the role of larger quantities of recombinant IL 2 given alone or in conjunction with in vitro-generated lymphokine-activated killer cells.
Immunoregulatory T cell circuits in man. Identification of a distinct T cell subpopulation of the helper/inducer lineage that amplifies the development of alloantigen-specific suppressor T cells.
Authors: Damle N K , Mohagheghpour N , Kansas G S , Fishwild D M , Engleman E G 
Published: December 2022

Abstract
Regulation of the immune response in man is dependent on interactions between cells of helper/inducer (Leu-3+/T4+) lineage and cells of suppressor/cytotoxic (Leu-2+/T8+) lineage. By using the mixed leukocyte reaction (MLR) as a model system, we have shown previously that alloantigen-primed Leu-3+ cells induce autologous Leu-2+ cells to differentiate into suppressor T cells that specifically inhibit the response of fresh T cells to the original allogeneic stimulator cells. The current study was undertaken to analyze the roles in this suppressor circuit of subpopulations of Leu-3+ cells distinguished from one another on the basis of their binding or lack of binding to monoclonal anti-Leu-8 antibody. Although both Leu-3+,8- and Leu-3+,8+ T cells proliferated in allogeneic MLR, alloactivated Leu-3+,8+ cells alone induced proliferation and differentiation of Leu-2+ suppressor cells. Leu-3+,8+ cells also induced Leu-3+,8- cells to proliferate, and following their activation in this manner, such autoactivated Leu-3+,8- cells augmented the differentiation of Leu-2+ suppressor cells, but only in the presence of alloactivated Leu-3+,8+ cells. Furthermore, this effect, like the suppressor effect, was specific for the inducer cells, and thus indirectly for the HLA-DR antigens of the original allogeneic stimulator cells as well. These results indicate that alloantigen-primed Leu-3+,8+ cells not only activate specific Leu-2+ suppressor cells but also activate specific Leu-3+,8- suppressor-amplifier cells, and in combination, these cells exert potent feedback inhibition of MLR.
The human thymic microenvironment. Phenotypic characterization of Hassall's bodies with the use of monoclonal antibodies.
Authors: Lobach D F , Scearce R M , Haynes B F 
Published: December 2022

Abstract
The human thymic microenvironment is important in promotion of T cell maturation, particularly during early stages of thymic ontogeny. Hassall's bodies (HB) are epithelial swirls in the human thymic medulla that are thought to be derived from endocrine medullary thymic epithelium. To study the ontogeny and function of various components of the human thymic microenvironment, we have produced four monoclonal antibodies (TE-8, TE-15, TE-16, and TE-19) that selectively reacted in thymus with HB. Antibodies TE-8 and TE-16 reacted with the cells forming the outer rim of the HB swirl. Antibody TE-19 reacted with the entire cellular portion of HB and with epithelial cells immediately surrounding HB. Granular foci in the cellular swirls of greater than 90% of HB reacted with antibody TE-15. During thymic ontogeny, the antigens defined by antibodies TE-8, TE-15, TE-16, and TE-19 were first detected in fetal thymus on HB beginning at 16 wk gestation, the age when HB morphologically appear in the thymus. Aberrant expression of the antigens corresponding to antibodies TE-8, TE-15, TE-16, and TE-19 was observed on thymic tissue from individuals with severe cellular immunodeficiency disease. In human skin, antibodies TE-8, TE-16, and TE-19 reacted with the stratum granulosum; antibody TE-15 reacted with the stratum corneum. Thus, with the use of antibodies TE-8, TE-15, TE-16, and TE-19, we have identified HB as antigenically distinct regions of endocrine thymic epithelium. Furthermore, we have shown that these anti-HB reagents also selectively react with epidermal keratinocytes in the terminal stages of keratinocyte maturation.
Biochemical models of gamma-interferon action: altered expression of transferrin receptors on murine peritoneal macrophages after treatment in vitro with PMA or A23187.
Authors: Weiel J E , Adams D O , Hamilton T A 
Published: December 2022

Abstract
The number of transferrin receptors in thioglycollate-elicited murine peritoneal macrophages is markedly depressed after exposure to murine gamma-interferon (IFN gamma) in vitro. This change has been used as a model system to study the molecular and cellular mechanisms of IFN gamma signal transduction. We observed that the downshift of the transferrin receptor could be mimicked by exposure to the calcium ionophore (A23187) or the potent tumor promoter, phorbol 12-myristate 13-acetate (PMA). Saturation binding studies on thioglycollate (TG)-elicited peritoneal macrophages after exposure to A23187 or PMA showed the reduced expression of transferrin binding activity attributable to a decrease in the total number of cellular transferrin receptors and not an alteration in receptor-ligand affinity, in agreement with previous results obtained after exposure to IFN gamma. The loss of transferrin receptors in response to A23187 or PMA was dose dependent, and the kinetics of the change were identical to those observed with IFN gamma treatment. Phorbol 12,13-dibutyrate or 4-beta-phorbol 12,13-didecanoate, both biologically active phorbol esters, also induced reduced expression of transferrin receptors, whereas nonesterified phorbol or 4-alpha-phorbol 12,13-didecanoate, an inactive phorbol ester, had no effect on transferrin receptor expression. Finally, PMA and A23187, when used together, acted cooperatively to modulate transferrin receptor expression when both agents were present at subthreshold concentrations. These results, taken together, suggest that elevation of intracellular Ca++ levels and/or stimulation of protein kinase C are involved in the response of macrophages to IFN gamma.
Studies on the synthesis and secretion of interleukin 1. I. A 33,000 molecular weight precursor for interleukin 1.
Authors: Giri J G , Lomedico P T , Mizel S B 
Published: December 2022

Abstract
Previous studies have suggested that murine interleukin 1 (IL 1) may be synthesized as a high m.w. precursor. Using specific antibodies against murine IL 1, we have analyzed the primary form of IL 1 synthesized by normal peritoneal macrophages and P388D1 cell line macrophages, and in vitro using poly (A)+ RNA from stimulated normal and cell line macrophages. In all cases, the labeled protein immunoprecipitated with the anti-IL 1 antibodies exhibited a m.w. of 33,000 on SDS gels. This 33,000 m.w. protein was not an aggregate of low m.w. IL 1. Addition of excess purified low m.w. IL 1 completely blocked the immunoprecipitation of the 33,000 m.w. protein. When cells were pulsed with [35S]methionine for 1 to 5 hr and then incubated in medium containing unlabeled methionine for 19 hr, labeled low m.w. IL 1 was detected in the culture fluid. If cells were pulsed with [35S]methionine to label the 33,000 m.w. protein and then incubated in the presence of a maximally effective concentration of the protein synthesis inhibitor, cycloheximide, the low m.w. IL 1 was still found in the culture fluid. Our results indicate that IL 1 is synthesized as a 33,000 m.w. precursor that is converted to the low m.w. form that is found in the culture fluid of stimulated murine macrophages.
Identification and characterization of a B cell growth inhibitory factor (BIF) on BCGF-dependent B cell proliferation.
Authors: Kawano M , Iwato K , Kuramoto A 
Published: December 2022

Abstract
The culture supernatants of Con A-activated human peripheral blood mononuclear cells (PBM) contained at least two regulatory factors upon B cell proliferation. One was B cell growth factor (BCGF), which activated antigen-stimulated B cells to proliferation and clonal expansion, and the other was its inhibitory factor, arbitrarily named B cell growth inhibitory factor (BIF). This BIF inhibited the effect of BCGF on anti-mu-stimulated B cells or the monoclonal mature B cell line (CLL-T.H.) obtained from the peripheral blood lymphocytes of B cell-type chronic lymphocytic leukemia patients, which were activated only with BCGF and without adding other proliferating stimuli (e.g., anti-mu). BIF activity was detected in the 24 hr culture supernatants of Con A-activated human PBM in FCS containing medium and also in serum-free RPMI 1640 medium. This substance with BIF activity could not be derived from FCS. Con A-induced BIF (m.w. of 80,000 and an isoelectric point of pH 5.4) was analyzed by Sephadex G-200 gel filtration and chromatofocusing. BIF was stable at pH 2.0 and at 56 degrees C for 30 min. Partially purified BIF had no effect on cell viability and almost no interferon activity (less than 1 IU/ml). BIF with high titer had a slight but significant inhibition on TCGF-dependent T cell growth and on PHA or Con A responses, but the extent of these inhibitions was far less than that of BCGF-dependent B cell growth. Absorption of BIF with Con A blasts made its inhibition on T cell growth even less. On the other hand, BIF activity could not be absorbed with Con A blasts but was almost absorbed with large numbers of CLL-T.H. cells. BIF had almost no inhibitory effect on the proliferation of a mouse fibroblast cell line (NIH 3T3), a mouse myeloma cell line (NS-1), human lymphoid cell lines (MOLT-4, HSB-2, and Daudi), or a human myeloid cell line (K-562). BIF-producing cells were estimated to be T cells and were identified as T8+ T cells. On the other hand, Con A-induced BCGF was demonstrated to be produced predominantly by T4+ T cells. These results show that human B cell proliferation is regulated by interaction between T4+ and T8+ cells via soluble factors, namely BCGF and BIF, respectively.
Lymphokine-mediated induction of cytolytic activity in a T cell hybridoma.
Authors: Kanagawa O , Chiller J M 
Published: December 2022

Abstract
Functionally inducible CTL hybridomas were constructed by fusing alloantigen-specific T cells (C57BL/6 alpha-DBA/2) with cells from the rat thymoma line W/FU (C58NT)D. A cloned hybridoma line (KSH.4.13.6) that was specifically cytolytic in the presence of activated rat spleen cell supernatant fluid (rat Con A SN) lost activity when transferred to normal medium. However, a cytolytic activity could be reinduced by culturing KSH.4.13.6 cells in medium containing rat Con A SN or secondary mixed leukocyte culture SN. By using various sources of SN, it was found that cytolytic induction required two different factors. PMA-induced EL-4 SN and SN from antigen-activated cloned T cells, neither of which were capable of inducing cytolytic activity alone, were able to synergize in the cytolytic induction of KSH.4.13.6 IFN-gamma and IL 1 failed to induce cytolytic activity even in the presence of EL-4 SN. Furthermore, this hybridoma produced macrophage activating factor (MAF) upon culture in rat Con A SN, although MAF production could not be induced by either specific antigen or lectins. The kinetics of induction and loss of cytolytic activity mediated by rat Con A SN were similar to those of the induction of MAF production. However, EL-4 SN, which by itself was incapable of inducing cytolytic activity, was able to induce MAF production in the KSH.4.13.6 hybrid to an extent similar to that induced by rat Con A SN. These results suggest that the induction of cytolytic activity and of MAF production in this cloned hybridoma cell line are regulated by different mechanisms. Such a functionally inducible T cell hybrid may provide a tool for biochemical and molecular analysis of T cell function and regulation, and of the characterization of cytokines required for CTL differentiation.