bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myelin basic protein and proteolipid protein reactivity of brain- and cerebrospinal fluid-derived T cell clones in multiple sclerosis and postinfectious encephalomyelitis.
Authors: Hafler D A , Benjamin D S , Burks J , Weiner H L 
Published: December 2022

Abstract
T cells were directly cloned from autopsied MS brain plaque tissue and reactivity was measured with the major encephalitogenic neuroantigens, myelin basic protein (MBP), and proteolipid protein (PLP). Control clones were simultaneously derived from the blood. The proportion of T4+ and T8+ T cell clones from the brain tissue differed from that of peripheral blood T cell clones derived at the same time, suggesting that the clones were not derived from the peripheral blood. None of 57 brain-derived T cell clones proliferated to either MBP or PLP, although they responded well to PHA and IL 2. An additional 235 clones derived from the cerebrospinal fluid and 126 clones from the peripheral blood of other subjects with multiple sclerosis also did not proliferate to MBP or PLP. In contrast, five of nine T4+ clones from the CSF of a subject with postinfectious encephalomyelitis exhibited low but clear reactivity to human MBP, supporting the possible role of MBP as the target antigen in this disease. These studies, the first to clone T cells directly from MS plaque tissue, suggest that the lack of consistent T cell reactivity to MBP or PLP in the peripheral blood of MS patients does not appear to be secondary to the sequestration of a large number of these cells in the brain.
Allogeneic matings and immunization have different effects on nulliparous and multiparous mice.
Authors: Chavez D J , McIntyre J A , Colliver J A , Faulk W P 
Published: December 2022

Abstract
CBA/J female mice have a high rate of spontaneous fetal loss when mated with DBA/2 males. We have confirmed that this fetal resorption rate can be significantly reduced by immunizing the female with C57BL rather than DBA leukocytes. The current studies have been extended to show the effect of continued immunization into second pregnancies. Three new findings emerge: second pregnancies in unimmunized CBA/J females X DBA/2 males proceed with a low percentage of spontaneous resorptions; continued immunization of multigravid, multiparous mice is associated with a high percentage of late onset fetal resorptions; and comparison of sex ratios between treated and untreated pregnancies showed no significant shift. These results suggest that untreated CBA/J females mated to DBA/2 males can be immunized to trophoblast antigens during first pregnancies, and that such immunization leads to "normal" reproductive outcome in subsequent untreated pregnancies. Persistent immunization with leukocytes appears to increase the percentage of fetal wastage in subsequent pregnancies regardless of whether the mother receives paternal or nonpaternal leukocytes. Intentional chronic immunization with male leukocytes does not influence the sex ratio of viable offspring. These data are discussed with reference to immunotherapy for women who suffer unexplained, recurrent spontaneous abortions.
The influence of valence on the functional activities of monoclonal anti-L3T4 antibodies. Discrimination of signaling from other effects.
Authors: Haque S , Saizawa K , Rojo J , Janeway C A 
Published: December 2022

Abstract
Anti-L3T4 antibodies have different functional effects on different ligands that activate a cloned, L3T4+ helper T cell line. It is reported here that some of these effects involve positive or negative signaling induced by cross-linking L3T4 molecules, because such effects are not observed using the Fab fragment of anti-L3T4. However, the Fab fragment does inhibit responses to antigen:self class II major histocompatibility complex (MHC) and to anti-T cell receptor monoclonal antibodies directed at a particular V region epitope. The finding that the Fab fragment of anti-L3T4, which does not block binding of anti-T cell receptor V region antibodies and does not negative signal can still block activation by such antibodies suggests an intimate association of L3T4 with the T3: alpha: beta T cell receptor complex. This association may normally be induced by interaction of both structures with antigen:self class II MHC complexes. The data also support the hypothesis that cross-linking the L3T4 molecule in the absence of engagement of the T3: alpha: beta complex generates negative or inhibitory signals. Thus, L3T4 plays a central role in the process of class II MHC-restricted T cell antigen recognition and activation.
Modification of the cytotoxic T cell repertoire in neonatal tolerance. Evidence for preferential survival of cells with low avidity for tolerogen.
Authors: Wood P J , Socarras S , Streilein J W 
Published: December 2022

Abstract
Clonal deletion of developing lymphocytes with potential reactivity for self is thought to play a crucial role in the establishment of self tolerance. One prediction of the clonal deletion hypothesis is that cells bearing receptors with high affinity for self are more likely than cells with low affinity receptors to be deleted from the repertoire. Experimental models of B cell tolerance have provided evidence for the preferential survival of low affinity cells with specificity for tolerogen in tolerant animals, but no comparable evidence exists for T cells. To examine this issue in T cells, cytotoxic T cell lines specific for the Kb mutant class I H-2 molecule, bm1, were generated from C57BL/6 mice rendered neonatally tolerant of bm1 and compared with anti-bm1 lines generated from normal mice. Compared with normal lines, those from tolerant mice differed in five ways: 1) they grew more slowly; 2) they were less efficient at lysing bm1 targets; 3) they showed different patterns of lysis against a panel of third party targets; 4) their cytotoxic activity against bm1 could be increased in the presence of leukoagglutinin, whereas the activity of normal lines was not increased by leukoagglutinin; and 5) their cytotoxic activity was more susceptible to inhibition by anti-Lyt-2 antibody. Taken together, these results demonstrate that the repertoire of the remaining tolerogen-specific cytotoxic T cells in neonatally tolerant mice is different from the normal C57BL/6 anti-bm1 repertoire, and the results are consistent with the idea that the remaining tolerogen-specific cells are low avidity cells that have preferentially escaped the clonal deletion process.
Role of B cell stimulatory factor 1/interleukin 4 in clonal proliferation of B cells.
Authors: Peschel C , Green I , Ohara J , Paul W E 
Published: December 2022

Abstract
B cell stimulatory factor 1 (BSF-1)/interleukin 4 (IL-4) has striking effects on colony formation in soft agar by small resting B lymphocytes. BSF-1 alone induces colony formation in this cell population, presumably in costimulation with a mitogenic substance present in bacto-agar. In costimulation with anti-IgM antibodies, BSF-1 caused initial proliferation of 8 to 10% of B cells, resulting in a large number of cell clusters (10 to 40 cells/clone) after 3 to 4 days of incubation. However, substantial number of colonies (greater than 40 cells/clone) developed only from these clusters when IL-1 was added to the cultures. Using a modified immunoperoxidase staining technique for the determination of IgM allotype, evidence was obtained that B cell colonies stimulated with BSF-1 are derived from a single progenitor cell. Neutralization of BSF-1 with 11B11 after a culture period of 1 to 4 days inhibits further proliferation of B cell colonies, indicating that the action of BSF-1 extends for several cell generations beyond initial stimulation from the resting state. Furthermore, it is demonstrated that the synergistic action of IL-1 with BSF-1 is confined to the late culture period, indicating a growth-promoting effect by IL-1 for activated B cells.
Interferon-gamma is a major regulator of C1-inhibitor synthesis by human blood monocytes.
Authors: Lotz M , Zuraw B L 
Published: December 2022

Abstract
C1 inhibitor (C1INH) is the major control factor for the activation of the classical pathway of complement and for contact system activation. Hepatocytes and blood monocytes are known to synthesize this protease inhibitor. We studied the regulation of monocyte C1INH production by mediators that are generated during inflammatory responses. Purified blood monocytes spontaneously synthesized and secreted C1INH only after prolonged culture. In the presence of interferon (IFN)-gamma, C1INH was detectable within 24 hr and continued to be released at high levels throughout an 8-day culture period. Monocyte C1INH was newly synthesized and was functionally active as determined by forming stable complex with C1s. Other monocyte stimuli were either less potent (IFN-alpha, IFN-beta) or not capable of increasing C1INH release (lipopolysaccharide, interleukin 1, and tumor necrosis factor). The second component of complement, C2, was induced by IFN-gamma to a similar extent as C1INH. These findings demonstrate that IFN-gamma is a major regulator of monocyte C1INH production and may warrant consideration of IFN-gamma in the treatment of C1INH deficiency states.
Mapping of C2, Bf, and C4 genes to the swine major histocompatibility complex (swine leukocyte antigen).
Authors: Lie W R , Rothschild M F , Warner C M 
Published: December 2022

Abstract
Three miniature swine lines, inbred for swine leukocyte antigen (SLA) haplotypes, a, c, and d, and a recombinant line, haplotype g, were analyzed for possible restriction fragment length polymorphisms (RFLP) by Southern blot hybridization with human C2, factor B (Bf), and C4 specific probes. The search for RFLP by using a human C2 probe failed to reveal any variants. However, a Taq I polymorphism was identified with the human Bf probe and Bam HI and Pvu II polymorphisms were identified with the human C4 probe. Overlapping restriction fragments were found with the C2 and Bf probes, which strongly suggests close linkage of C2 and Bf genes in swine. Segregation analyses of the Bf and C4 polymorphisms indicated that the polymorphic fragments followed a Mendelian pattern of inheritance. The recombinant haplotype g, which expresses class I genes of haplotype c and class II genes of haplotype d, was shown to produce an identical RFLP pattern, by using the Bf and C4 probes, as haplotype d, but different from that of haplotype c. This indicates that there is a close association of [C4-Bf-C2] and class II genes in miniature swine. Although these data do not show conclusively the location of the [C4-Bf-C2] genes, it is hypothesized that swine [C4-Bf-C2] genes are located between the class II and class I genes, as has been demonstrated in mouse and man.
A human hybrid hybridoma.
Authors: Tiebout R F , van Boxtel-Oosterhof F , Stricker E A , Zeijlemaker W P 
Published: December 2022

Abstract
Hybrid hybridomas are obtained by fusion of two cells, each producing its own antibody. Several authors have reported the construction of murine hybrid hybridomas with the aim to obtain bispecific monoclonal antibodies. We have investigated, in a model system, the feasibility of constructing a human hybrid hybridoma. We fused two monoclonal cell lines: an ouabain-sensitive and azaserine/hypoxanthine-resistant Epstein-Barr virus-transformed human cell line that produces an IgG1 kappa antibody directed against tetanus toxoid and an azaserine/hypoxanthine-sensitive and ouabain-resistant human-mouse xenohybrid cell line that produces a human IgG1 lambda antibody directed against hepatitis-B surface antigen. Hybrid hybridoma cells were selected in culture medium containing azaserine/hypoxanthine and ouabain. The hybrid nature of the secreted antibodies was analyzed by means of two antigen-specific immunoassays. Our results show that it is possible, with the combined use of transformation and xenohybridization techniques, to construct human hybrid hybridomas that produce bispecific antibodies.
Kinetics and mechanisms of recombinant human interleukin 1 and tumor necrosis factor-alpha-induced changes in circulating numbers of neutrophils and lymphocytes.
Authors: Ulich T R , del Castillo J , Keys M , Granger G A , Ni R X 
Published: December 2022

Abstract
Human recombinant interleukins 1 alpha and 1 beta (rIL-1 alpha and -1 beta) both induced monophasic peripheral neutrophilia and lymphopenia in Lewis rats 1.5 hr after i.v. injection. The kinetics of rIL-1 alpha- and -1 beta-induced neutrophilia were similar to those induced by human monocyte-derived IL-1, IL-1 alpha, and IL-1 beta, and the peripheral neutrophilia was accompanied by a marked decrease in marrow neutrophils. Arachidonic acid metabolites are implicated as biochemical intermediates in the production of the neutrophilia but not lymphopenia, since indomethacin and dexamethasone both completely abrogated IL-1-induced neutrophilia but did not affect the IL-1-induced lymphopenia. Acetylsalicylic acid, a cyclooxygenase inhibitor, did not inhibit IL-1-induced neutrophilia, suggesting that products of the lipoxygenase rather than the cyclooxygenase pathway of arachidonate metabolism may contribute to the neutrophilia. Human recombinant tumor necrosis factor-alpha (rTNF) administered i.v. to Lewis rats induced peripheral neutropenia, two peaks of neutrophilia, and lymphopenia. A wide range of doses of rTNF resulted in an initial neutropenia at 0.5 hr after injection followed by a first peak of neutrophilia at 1.5 hr and a second peak of neutrophilia at 6 hr. The initial neutropenia and the first peak of neutrophilia were not inhibited by pretreatment of rats with dexamethasone, indomethacin, or aspirin. The second peak of neutrophilia was inhibited by both dexamethasone and indomethacin, but was not at all inhibited by aspirin, suggesting that the second peak of neutrophilia is mediated by the release of endogenous cytokines, especially by IL-1, since exogenous IL-1-induced neutrophilia is also completely inhibited by dexamethasone and indomethacin but not by aspirin. The TNF-induced peripheral neutrophilia is also accompanied by a significant depletion of bone marrow neutrophils, indicating that the source of increased circulating neutrophils is, at least in part, via recruitment of marrow neutrophils. Systemic blood pressure was not affected by IL-1 or rTNF at the dosages employed, showing that the changes in circulating leukocyte subsets were not attributable to hemodynamic changes nor to the hemodynamic change-related release of adrenal hormones. Adrenalectomy did not alter the IL-1- or rTNF-induced neutrophilia or lymphopenia, also demonstrating that neither monokine mediates its hematologic effects on peripheral blood leukocytes via the release of adrenal hormones.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of recombinant human granulocyte and macrophage colony-stimulating factors on signal transduction pathways in human granulocytes.
Authors: Sullivan R , Griffin J D , Simons E R , Schafer A I , Meshulam T , Fredette J P , Maas A K , Gadenne A S , Leavitt J L , Melnick D A 
Published: December 2022

Abstract
We studied the ability of the recombinant human-active hemopoietic growth factors granulocyte-macrophage colony-stimulating factor (GM-CSFrh) and granulocyte colony-stimulating factor (G-CSFrh) to activate receptor-mediated transduction pathways which have been implicated in the stimulation of cytotoxic functions in granulocytes. With the use of a panel of fluorescent probes, we found that these two growth factors exerted no detectable immediate effect on the resting transmembrane electrical potential, the intracellular concentration of free calcium ions, or the cytosolic pH of isolated, mature granulocytes. However, when granulocytes were "primed" by preincubation for 90 min with GM-CSFrh or G-CSFrh, the rate of membrane depolarization induced by 10(-7) M N-formyl-methionyl-leucyl-phenylalanine, but not the rate of rise in free calcium ions, was greatly accelerated. In examining potential mechanisms to account for the priming effect of these growth factors, we found that although they did not induce translocation of protein kinase C or stimulate significant degranulation, they each directly caused prompt release of arachidonic acid from plasma membrane phospholipids. Our data indicate that although GM-CSFrh and G-CSFrh do not activate the transduction signals that have most clearly been implicated in receptor-mediated activation of cytotoxic functions in granulocytes--namely, those coupled to membrane depolarization or release of intracellular calcium ions--they appear directly to induce the release of arachidonic acid esterified to membrane phospholipids, an event which may represent the receptor-mediated activation of membrane phospholipases and which may contribute to the "priming" of the cells for enhancement of their functional responsiveness.
Mouse bone marrow-derived mast cells cocultured with fibroblasts. Morphology and stimulation-induced release of histamine, leukotriene B4, leukotriene C4, and prostaglandin D2.
Authors: Levi-Schaffer F , Dayton E T , Austen K F , Hein A , Caulfield J P , Gravallese P M , Liu F T , Stevens R L 
Published: December 2022

Abstract
Mouse bone marrow-derived mast cells (BMMC), cultured for 2, 7, or 14 days in WEHI-3 conditioned medium in the absence or presence of mouse 3T3 fibroblasts, were examined morphologically and for their functional responses to IgE-Fc-mediated and calcium ionophore-mediated activation. The 7- and 14-day fibroblast-adherent and non-fibroblast-adherent populations of cocultured BMMC had more granules per cell and the granule contents were more electron dense than non-cocultured BMMC or BMMC cocultured for only 2 days. The adherent cocultured BMMC were usually located within multiple layers of fibroblasts, but did not form junctions with the fibroblasts. When activated immunologically, the adherent cocultured mast cells generally discharged their granules singly, but compound exocytosis was occasionally seen. Both the non-adherent cocultured BMMC and the BMMC that were cultured in the absence of fibroblasts were similar to one another in that they exocytosed 9 to 11% of their histamine when sensitized with anti-dinitrophenyl IgE and challenged with dinitrophenyl-bovine serum albumin and 27 to 29% of their histamine when challenged with calcium ionophore. In contrast, adherent cocultured BMMC exocytosed 27 and 61% of their histamine upon immunologic and calcium ionophore activation, respectively, representing a significant two- to three-fold increase relative to that obtained from the other populations of BMMC. When activated immunologically, BMMC cultured in WEHI-3 conditioned medium alone generated a mean of 12 ng of immunoreactive C-6-sulfidopeptide leukotrienes, 1.6 ng of leukotriene B4 (LTB4), and 1.0 ng of prostaglandin D2 (PGD2)/10(6) cells. The immunologic response of the nonadherent 7-day cocultured BMMC was similar. Fibroblast-adherent cocultured BMMC, on the other hand, generated 56 ng of immunoreactive C-6-sulfidopeptide leukotrienes, 6.4 ng of LTB4, and 5.6 ng of PGD2/10(6) mast cells, representing a significant increase for each product. When calcium ionophore was used as the agonist, the adherent cocultured mast cells also generated significantly more arachidonic acid metabolites than nonadherent cocultured BMMC or BMMC cultured in the absence of fibroblasts. Retention times on high performance liquid chromatography confirmed that the generated immunoreactive products were LTB4, PGD2, and LTC4. Thus, coculture of BMMC with fibroblasts induces an alteration in the composition of the secretory granules of the mast cells, as well as an augmentation of the activation-secretion response of the BMMC.(ABSTRACT TRUNCATED AT 400 WORDS)
N-formylpeptide-receptor dynamics, cytoskeletal activation, and intracellular calcium response in human neutrophil cytoplasts.
Authors: Omann G M , Swann W N , Oades Z G , Parkos C A , Jesaitis A J , Sklar L A 
Published: December 2022

Abstract
Cytoplasts (enucleated neutrophils which are depleted of dense granules) were prepared from human neutrophils with a modified procedure which employed dihydrocytochalasin B instead of cytochalasin B. These cytoplasts retained an activatable cytoskeletal network similar to cells in that filamentous actin polymerization in response to an N-formylpeptide (fluoresceinated N-formyl-nle-leu-phe-nle-tyr-lys, FLPEP) occurred with similar dose-response characteristics and was inhibitable by cytochalasin B and dihydrocytochalasin B. Cytoplasts had the same number of receptors per surface area as cells and binding constants and dissociation kinetics were the same for cells and cytoplasts. The conversion of receptors from a rapidly dissociating form to a slowly dissociating form was comparable in cells and cytoplasts. This conversion was not inhibited by cytochalasins and thus did not require actin polymerization. Cytoplasts were capable of internalizing 30% of bound FLPEP after 3 min of binding. Cytochalasins did not block this internalization which thus did not appear to require actin polymerization. After 5 min of binding, [3H]-N-formyl-met-leu-phe cosedimented with the Golgi marker enzymes when cytoplasts were fractionated on sucrose density gradients after N2 cavitation. These results indicate that the internalization mechanism is functional in cytoplasts. The Indo-1-detectable calcium response in cytoplasts had a ED50 similar to cells, though the maximum increase in Ca2+ concentration was about one-half that of cells. The response recovered with time after stimulation and the calcium detected was primarily from intracellular stores. The decay of responses after addition of formylpeptide antagonists was parallel for cells and cytoplasts, and leukotriene B4-induced responses in both cells and cytoplasts. Thus the regulation of the responses in cells and cytoplasts was analogous.
Aluminum fluoride induces phosphatidylinositol turnover, elevation of cytoplasmic free calcium, and phosphorylation of the T cell antigen receptor in murine T cells.
Authors: O'Shea J J , Urdahl K B , Luong H T , Chused T M , Samelson L E , Klausner R D 
Published: December 2022

Abstract
Antigen activation of murine T lymphocytes leads to phosphorylation of three subunits of the murine T cell antigen receptor (L.E. Samelson, M.D. Patel, A.M. Weissman, J.B. Harford, and R.D. Klausner. 1986. Cell 46:1083). Two kinases are activated in this process: protein kinase C which leads to phosphorylation of the gamma and, to a lesser extent, the epsilon subunits on serine residues and a tyrosine kinase which phosphorylates the p21 subunit (M.D. Patel, L.E. Samelson, and R.D. Klausner. 1987. J. Biol Chem. 262:5831). We sought to determine whether treatment of these cells with NaF could simulate any of these antigen-induced events. Indeed NaF treatment resulted in breakdown of polyphosphoinositides and production of phosphoinositols. This treatment also resulted in a rise in cytosolic free Ca2+. EGTA failed to block this rise suggesting that NaF liberated intracellular stores of Ca2+. Finally NaF treatment resulted in phosphorylation of the gamma and epsilon chains of the T cell receptor indistinguishable from the effects of phorbol esters. The NaF effect was potentiated by addition of A1Cl3 consistent with the view that the active moiety is A1F4-. The A1F4--induced phosphorylations were abolished in cells in which protein kinase C was depleted by prior treatment with phorbol myristate acetate. All of these observations are compatible with the interpretation that the A1F4- phosphorylation is mediated by protein kinase C. Antigen and anti-receptor antibody-induced receptor serine phosphorylation and phophatidylinositol turnover are blocked by raising intracellular levels of cyclic adenosine monophosphate. In contrast, A1F4--induced effects were insensitive to cyclic adenosine monophosphate.