bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of altered membrane structure on NK cell-mediated cytotoxicity. III. Decreased susceptibility to natural killer cytotoxic factor (NKCF) and suppression of NKCF release by membrane rigidification.
Authors: Roozemond R C , Mevissen M , Urli D C , Bonavida B 
Published: December 2022

Abstract
We have shown recently that alteration of the membrane fluidity of either effector or target cells results in significant and selective inhibition of NK cell-mediated cytotoxicity (NK CMC). However, the localization of the defective stage in the NK lytic pathway is not known. In the present study, we show that rigidification of the NK-sensitive U937 target cell membrane by lipid modulation reduces its sensitivity to lysis by NK cytotoxic factor (NKCF). This resistance was not due to loss of NKCF binding sites on the target cell because target cells with rigid membranes absorbed more NKCF than control cells. The enhanced ability to absorb NKCF by membrane modification was supported by data showing that NK-resistant Raji cells lacking NKCF-binding sites absorb NKCF after lipid modification. Furthermore, consistent with the lipophilic nature of NKCF, synthetic lipid vesicles absorb NKCF. In contrast to membrane rigidification, membrane fluidization of the target cell did not change the target cell properties. Rigidification of the NK effector cell membrane abrogates it ability to secrete active NKCF when stimulated by target cells or by mitogens. Membrane fluidization of the NK effector cells did not inhibit their ability to release NKCF. The results of these studies demonstrate that inhibition of NK CMC by rigidification of the target cell membrane results in cells that are inhibited in processing bound NKCF to lysis. Inhibition of NK CMC by rigidification of the NK effector cell results in defective trigger for activation of the NKCF release mechanism.
Novel immunosuppressive agent, FK506. In vitro effects on the cloned T cell activation.
Authors: Sawada S , Suzuki G , Kawase Y , Takaku F 
Published: December 2022

Abstract
The present study shows the in vitro effects of a novel immunosuppressive agent, FK506, in comparison with cyclosporin A (CsA). FK506 inhibited concanavalin A response and allo-mixed lymphocyte reaction of murine splenic lymphocytes in a dose-dependent manner, and at 40- to 200-fold lower concentrations than CsA. Allo-cytolytic T lymphocyte induction from murine thymocytes was also inhibited by FK506, whereas the ability of cytolytic T lymphocyte to lyse targets was not affected by the agent. Immunosuppressive effects of FK506 were further characterized by using antigen specific-proliferative T lymphocyte clones, BC.21 and KO.6. FK506 inhibited the proliferation of T cell clones stimulated with specific antigens in a dose-dependent manner, and at about 100-fold lower concentrations than CsA. However, cloned T cells, once activated, were scarcely affected by the agent; interleukin-2 (IL-2) driven proliferation of cloned T cells was not inhibited. On the other hand, it was found that FK506 inhibited both IL-2 secretion and IL-2 receptor expression of BC.21 after stimulation with the specific antigen. FK506 also inhibited the proliferation of BC.21 stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore, indicating that it directly affected the signaling pathway downward from the perturbation of the Ti/T3 complex. Finally, it was suggested that FK506 and CsA synergistically inhibited the antigen-driven proliferation of cloned T cells. These results indicate that the novel immunosuppressive agent, FK506, affects T cell activation with mechanisms similar to those of CsA but at considerably lower concentrations.
Ly-1 B helper cells in autoimmune "viable motheaten" mice.
Authors: Sherr D H , Dorf M E , Gibson M , Sidman C L 
Published: December 2022

Abstract
Previous work has demonstrated that Ly-1 B cells from normal C57BL/6J mice help the response of B cell subsets to the 4-hydroxy-3-nitrophenylacetyl hapten (NP). This regulatory cell population, called BH, preferentially helps the expression of plaque-forming B cells which express a predominant set of serologically related determinants collectively known as the NPb idiotype family. The specificity of BH cell activity in the NP system is a reflection of NPb idiotype-specific BH cell surface receptors. Thus, BH cells recognize autologous (i.e., idiotype) antigens. Given these observations and previous associations of increased Ly-1 B cell frequency in autoimmune mice, it was hypothesized that autoreactive Ly-1 BH cells may be present in high frequencies and in an activated state in autoimmune mice. To test this hypothesis the immunologic activity of BH cells in autoimmune viable motheaten (mev/mev) mice was studied. It was determined that splenic BH cells are approximately 10 times more frequent in viable motheaten than normal mice. The fact that BH cells from viable motheaten mice are activated was suggested by the presence of NPb idiotype-specific BH replacing helper activity in sera or B cell supernatants from these autoimmune mice. The soluble helper activities constitutively produced in mev/mev splenic B cell cultures and detected in mev/mev serum were resolved into two moieties, an NPb idiotype-specific immunoglobulin and a nonimmunoglobulin lymphokine(s) fraction. Purified mev/mev B cell-derived B cell maturation factor could substitute for the lymphokine moiety in the NPb idiotype helper cell assay. These results suggest that at least two signals, anti-idiotype immunoglobulin and a late-acting B cell maturation factor, are required for BH-dependent helper activity. The relationships of these results to current concepts of B cell activation mechanisms and the possible association of Ly-1 BH cells with autoimmunity are discussed.
Characterization of adult human marrow hematopoietic progenitors highly enriched by two-color cell sorting with My10 and major histocompatibility class II monoclonal antibodies.
Authors: Lu L , Walker D , Broxmeyer H E , Hoffman R , Hu W , Walker E 
Published: December 2022

Abstract
Monoclonal antibodies, My10 (HPCA-1) and major histocompatibility class II (HLA-DR), were used to enrich and phenotype normal human marrow colony-forming unit: granulocyte-macrophage (CFU-GM), burst-forming unit: erythroid (BFU-E), and multipotential colony-forming unit: granulocyte-erythroid-macrophage-megakaryocyte (CFU-GEMM) progenitor cells. Nonadherent low density T lymphocyte-depleted marrow cells were sorted on a Coulter Epics 753 dye laser flow cytometry system with the use of Texas Red-labeled anti-My10 and phycoerythrin conjugated anti-HLA-DR. Cells were separated into populations with nondetectable expression of antigens (DR-My10-) or with constant expression of one antigen and increasing densities of the other antigen. More than 98% of the CFU-GM, BFU-E, and CFU-GEMM were found in fractions containing cells expressing both HLA-DR and My10 antigens. The cloning efficiency (CE) of cells in the DR-My10- cell fraction was 0.01%. In the antigen-positive sorted fractions, the CE was highest (up to 47%) in the fractions of cells expressing high My10 and low DR (My10 DR+) antigens and was lowest (2.5%) in the fraction of cells expressing low My10 and low DR (My10+DR+) antigens. Populations of cells varying in the density of HLA-DR, but not My10, antigens varied in the proportion and types of progenitor cells present. When My10-positive cells were sorted for HLA-DR density expression, the CE for CFU-GM was similar in the DR+ and DR++ fractions, but most of the BFU-E and CFU-GEMM were found in the DR+ fraction. Within the CFU-GM compartment, most of the eosinophil progenitors were found in the DR+ fraction, whereas a greater proportion of macrophage progenitors were detected in the DR++ fraction. CFU-GM and BFU-E in the fractions of cells positive for DR and My10 were assessed for responsiveness to the effects of recombinant human tumor necrosis factor-alpha, recombinant human interferon-gamma, and prostaglandin E1. Colony formation from CFU-GM was suppressed by the three molecules, and colony formation by BFU-E was suppressed by recombinant human tumor necrosis factor-alpha and interferon-gamma and enhanced, in the presence of T lymphocyte-conditioned medium, by prostaglandin E1 in all antigen-positive fractions.(ABSTRACT TRUNCATED AT 400 WORDS)
Comparison of antigen specificity, class II major histocompatibility complex restriction, and in vivo behavior of myelin basic protein-specific T cell lines and clones derived from (BALB/c x SJL/J) mice.
Authors: Trotter J , Zamvil S S , Steinman L 
Published: December 2022

Abstract
Immunization with myelin basic protein (BP) causes experimental allergic encephalomyelitis (EAE) in certain strains of mice. SJL/J (H-2s) is the prototype sensitive strain. Although BALB/c (H-2d) is resistant to EAE through use of an identical immunization protocol, (BALB/c x SJL/J)F1 hybrid mice develop EAE after immunization with BP. T cell clones specific for BP have been isolated from a highly encephalitogenic line of (BALB/c x SJL/J)F1 hybrid T cells raised against bovine BP. The clones were examined for their H-2 restriction and specificity for heterologous forms of BP (mouse, rat, and bovine BP). The results revealed the clones cross-reacting with mouse (self) BP were almost always restricted to F1 hybrid class II major histocompatibility complex (MHC) elements. In contrast, mouse cross-reactive clones derived from a nonencephalitogenic (BALB/c x SJL/J) T cell line raised against rat BP were largely restricted to H-2d elements. These clones did not cross-react with bovine BP. Four additional lines were generated by carrying the original rat and bovine F1 T cell lines on parental antigen-presenting cells thus generating lines biased toward homozygous (SJL/J, H-2s, or BALB/c, H-2d) restriction elements. These "parentally restricted" T cell lines did not induce EAE when injected in vivo. These results suggest that in this F1 strain sensitivity to T cell-induced EAE is associated with epitopes on murine BP that associate with F1 class II MHC restricting elements. In contrast, nonencephalitogenic T cell lines contain a high proportion of murine cross-reactive clones restricted to H-2d, the haplotype of the classically resistant BALB/c mouse. This work illustrates the use of T cell lines and clones in a model system to further analyze the role of MHC restriction elements in autoimmune disease occurring in heterozygous individuals.
Interleukin 2 inhibits in vitro granulocyte-macrophage colony formation.
Authors: Naldini A , Fleischmann W R , Ballas Z K , Klimpel K D , Klimpel G R 
Published: December 2022

Abstract
We have previously shown that murine bone marrow cells cultured with interleukin 2 (IL-2) produce interferon-alpha/beta (MuIFN-alpha/beta) and that IFN-alpha/beta can suppress in vitro granulocyte-macrophage colony-forming cell formation (GM-CFC). In this study, IL-2 was directly assessed for its ability to inhibit in vitro granulocyte and/or macrophage colony-forming cell formation (GM-CFC/M-CFC). C57BL/6 bone marrow cells were cultured with different colony-stimulating factors (CSF), i.e., partially purified macrophage-CSF (M-CSF) or recombinant granulocyte and macrophage CSF (GM-CSF) in the presence or absence of different IL-2 preparations. Partially purified mouse IL-2 or recombinant human or mouse IL-2 (rHuIL-2 and rMuIL-2) totally inhibit GM-CFC and M-CFC formation at 7 days of culture. The level of inhibition mediated by IL-2 was concentration-dependent, with as little as 1 U/ml giving total inhibition of colony formation. The ability of IL-2 to inhibit colony formation was completely abolished by treatment with antisera to IL-2. MuIFN-alpha/beta and MuIFN-gamma appeared to play no role in IL-2-induced myelo-suppression in that addition of antisera to these IFN failed to block IL-2-induced suppression. Myelo-suppression mediated by IL-2 was independent of the concentration of CSF used in the bone marrow cultures. Suppression was also not dependent upon the initial presence of T cells or natural killer (NK) cells. Bone marrow cells depleted of Thy-1+, Lyt-1+, Lyt-2+, NK-1.1+, Asialo GM1+, or Qa-5+ cells were as susceptible to IL-2 induced suppression as untreated or complement-treated bone marrow cells. These results suggest that IL-2 may play an important role in regulating different aspects of hematopoiesis.
Tumor necrosis factors alpha and beta differ in their capacities to generate interleukin 1 release from human endothelial cells.
Authors: Locksley R M , Heinzel F P , Shepard H M , Agosti J , Eessalu T E , Aggarwal B B , Harlan J M 
Published: December 2022

Abstract
The capacity of the tumor necrosis factors, TNF-alpha and TNF-beta, products of activated macrophages and lymphocytes, respectively, to stimulate interleukin 1 (IL-1) release from endothelial cells derived from human umbilical veins was examined in vitro. Recombinant TNF-alpha caused IL-1 release by 4 hr with maximal levels of 17 U/ml by 24 hr; half-maximal stimulation occurred at approximately 80 pM. In contrast, recombinant TNF-beta was a relatively poor stimulus for IL-1 release. Even at concentrations as high as 600 pM, only 3 U of IL-1/ml were recovered; maximal IL-1 release (10 to 12 U/ml) required up to 5 nM TNF-beta. Natural, glycosated human TNF-beta was comparable in activity to recombinant TNF-beta. TNF-beta did not directly inhibit the IL-1 comitogenesis assay, nor was there evidence that TNF-beta induced the release of an IL-1 inhibitor, in that supernatants generated in the presence of TNF-beta did not inhibit thymocyte proliferation to a recombinant IL-1 standard. Binding of the recombinant TNF to endothelial monolayers was assessed by using [125I]TNF-alpha in competition studies with cold TNF-alpha and TNF-beta. Binding of TNF-alpha was half-maximal at 80 pM with an average of 664 receptors/cell and Kd = 0.043 nM. Although TNF-beta was capable of fully competing for [125I]TNF-alpha binding, half-maximal binding occurred at 800 pM TNF-beta. These data suggest that the TNF receptors on human endothelial cells may reflect the structural differences between these two homologous cytokines.
Interleukin 1 induces interleukin 1. I. Induction of circulating interleukin 1 in rabbits in vivo and in human mononuclear cells in vitro.
Authors: Dinarello C A , Ikejima T , Warner S J , Orencole S F , Lonnemann G , Cannon J G , Libby P 
Published: December 2022

Abstract
Interleukin 1 (IL-1) plays an important role in host defense mechanisms by increasing body temperature, inducing the synthesis of a variety of lymphokines and hepatic acute phase proteins and acting as a chemoattractant for lymphocytes. However, in some microenvironments such as injured tissue or joint spaces, elevated IL-1 levels may contribute to pathologic processes, for example, proliferation and fibrosis of tissue involved in pannus formation as well as degradation of matrix and abnormal tissue architecture. To investigate potential mechanisms that may lead to excessive production of IL-1, we have examined the ability of IL-1 to participate in an amplification event by inducing its own gene expression leading to synthesis of biologically active IL-1. When injected into rabbits, recombinant human IL-1-alpha induced biphasic fevers, and during the second temperature elevation 3 hr later, a circulating pyrogenic material was detected by passive transfer of plasma to other rabbits. Induction of the biphasic fever was not caused by endotoxin contamination of the recombinant IL-1. The 3-hr circulating pyrogen was heat-labile and was not residual injected IL-1-alpha. Chromatographic separation of this plasma and biologic assay suggested that it was new IL-1 of rabbit origin. We next incubated human blood mononuclear cells with recombinant IL-1-alpha and measured the intracellular and extracellular levels of IL-1 by bioassay using the D10.G4.1 murine T cell line. In order to control for the carryover of recombinant IL-1-alpha used to stimulate the mononuclear cells (MNC), we used neutralizing antibodies that were specific for IL-1-alpha or IL-1-beta. The results of these neutralizations showed that recombinant human IL-1-alpha induces the synthesis of IL-1-beta in human MNC in vitro. These results were verified with a radioimmunoassay specific for IL-1-beta. At concentrations of 100 ng/ml, IL-1-alpha induced prostaglandin E2 production in the MNC culture, and this was associated with decreased production of immunoreactive IL-1-beta. Adding indomethacin to the cultures prevented the decreased production of IL-1-beta induced by high concentrations of IL-1-alpha. Using nonadherent MNC, we observed an increase in IL-1-beta as well as IL-1-alpha mRNA after 4 hr of exposure to recombinant IL-1-alpha. These results demonstrate that IL-1-alpha induces biologically active and immunoreactive IL-1-beta from MNC in vitro and that the same concentrations of IL-1-alpha induce gene expression for both forms of IL-1.(ABSTRACT TRUNCATED AT 400 WORDS)
Requirement for BSF-1 in the induction of antigen-specific B cell proliferation by a thymus-dependent antigen and carrier-reactive T cell line.
Authors: Dubois P , Stein P , Ennist D , Greenblatt D , Mosmann T , Howard M 
Published: December 2022

Abstract
We report here a role of B cell stimulatory factor 1 (BSF-1) in the induction of antigen-specific proliferation of affinity-purified small B lymphocytes by a thymus-dependent antigen and a carrier-reactive T cell line. By using an ovalbumin-reactive T cell line (designated Hen-1), which does not produce BSF-1 following activation, it was possible to demonstrate that the antigen-specific proliferative response of trinitrophenyl (TNP)-binding B cells to TNP-ovalbumin required exogenous BSF-1 in addition to direct interaction with irradiated Hen-1 T cells. The activation obtained under these conditions was highly efficient, being sensitive to antigen doses as low as 0.001 microgram/ml. The addition of saturating amounts of BSF-1 did not alter the antigen-specificity or the requirements for hapten-carrier linkage or major histocompatibility complex-restricted T-B interaction in this system. The involvement of BSF-1 was confirmed by the ability of 11B11 anti-BSF-1 antibody to specifically suppress the response of TNP-binding B cells to TNP-ovalbumin, BSF-1, and irradiated Hen-1 T cells. Finally, this response was augmented by addition of the monokine interleukin 1. These data indicate that the proliferative response of small B cells to the thymus-dependent antigen and carrier-reactive T cell line used in our experiments can be regulated by the same factors that govern B cell proliferation induced by thymus-independent type 2 antigens or anti-IgM antibodies.
Polypeptide fragments of horse cytochrome c activate a small subset of secondary B lymphocytes primed against the native protein.
Authors: Jemmerson R 
Published: December 2022

Abstract
Horse cytochrome c (cyt c) and two large, overlapping cyanogen bromide-cleaved fragments (1-80 and 66-104), together encompassing the entire length of the polypeptide chain, were examined for their abilities to stimulate into antibody production individual secondary B lymphocytes primed against the intact protein. T cell help was provided against the carrier protein, hemocyanin, to which cyt c and its peptides were conjugated by using glutaraldehyde. All the B cells activated by both of the fragments elicited antibodies that reacted with intact cyt c in enzyme-linked immunosorbent assay, whereas only a fraction of the antibodies elicited by the intact protein reacted with the peptides. However, in general, antibodies reactive with the polypeptide fragments, whether elicited by the intact protein or by the fragments, could not be effectively inhibited from binding plate-bound cyt c in enzyme-linked immunosorbent assay in the presence of soluble native cyt c. This indicates that these antibodies are specific for denatured forms of cyt c that apparently arise during the chemical coupling of cyt c to carrier molecules for immunization and/or during emulsification of the immunogen in adjuvant. Whereas, at most, 5% of the secondary B cells specific for native cyt c could be activated by the 1-80 fragment, even fewer were activated by the 66-104 fragment. Therefore, it is unlikely that smaller peptides which fail to assume native conformation would be effective. Antibodies elicited in vivo in a primary response to the 1-80 fragment also failed to bind native cyt c. These results suggest that linear peptides intended to mimic epitopes on globular proteins, and which have not been engineered to adopt native conformation, will not be very effective either as primary or as secondary vaccines for B cell activation.
Xyloside inhibits synthesis of the class II-associated chondroitin sulfate proteoglycan and antigen presentation events.
Authors: Rosamond S , Brown L , Gomez C , Braciale T J , Schwartz B D 
Published: December 2022

Abstract
An alternative form of the human invariant chain exists as a chondroitin sulfate proteoglycan (CSPG) with invariant chain as the core protein. The selective inhibitor of proteoglycan synthesis, p-nitrophenyl beta-D-xyloside was used to study the role of this CSPG in class II biology. At xyloside concentrations of 2.5 and 5.0 mM, CSPG synthesis was completely inhibited with marginal inhibition of protein synthesis. The inhibitory effect on CSPG synthesis was completely reversible. The number of class II molecules on the cell surface was not affected by xyloside, but biosynthesis and appearance of newly synthesized class II molecules at the cell surface were both decreased by xyloside. Recognition of influenza virus-infected cells by class II-restricted, virus-specific cytotoxic T lymphocytes was not diminished by the presence of xyloside in the effector phase of the cytotoxicity assay. However, sensitization of target cells was markedly inhibited when target cells were exposed to virus in the presence of xyloside. These results are consistent with the hypothesis that the CSPG form of invariant chain has a role in antigen processing.
Trace levels of bacterial lipopolysaccharide prevent interferon-gamma or tumor necrosis factor-alpha from enhancing mouse peritoneal macrophage respiratory burst capacity.
Authors: Ding A H , Nathan C F 
Published: December 2022

Abstract
Preexposure of resident mouse peritoneal macrophages for 1 hr to traces of bacterial lipopolysaccharide (LPS) (less than or equal to 1 ng/ml) rendered the cells refractory to activation by recombinant interferon-gamma (rIFN gamma) or recombinant tumor necrosis factor-alpha (rTNF alpha), as evaluated by release of H2O2 upon stimulation with phorbol myristate acetate. Inhibition persisted for at least 4 days. Fifty percent inhibition of activation mediated by rIFN gamma followed 1 hr exposure to 10 pg/ml LPS. Fifty percent inhibition of activation mediated by rTNF alpha was achieved with 1 hr exposure to 1 pg/ml LPS. Such low levels LPS exposures (concentration X time) are far below those reported for many other actions of LPS on host cells. Inhibition was partially prevented by the cyclooxygenase inhibitors indomethacin, ibuprofen, and acetylsalicylic acid. Exogenous prostaglandins PGE1 and PGE2, and the 3',5'-cyclic adenosine monophosphate analog dibutyryl cyclic adenosine monophosphate (cAMP), mimicked the inhibitory effect of LPS in a dose-dependent manner, consistent with the hypothesis that formation of endogenous cyclooxygenase products in response to LPS may elevate intracellular cAMP and that the latter may mediate the observed inhibition. In addition, neutralizing antibody against IFN alpha and IFN beta selectively prevented LPS inhibition of activation mediated by rIFN gamma, but not by rTNF alpha. This suggests that IFN alpha and/or IFN beta induced by LPS also contributed to inhibition of activation by rIFN gamma. Thus, release of LPS may afford microorganisms a means by which to interfere with immunologically mediated enhancement of the respiratory burst-dependent antimicrobial capacity of macrophages.