bluuebunny/crossref_metadata_2025 huggingface dataset:
Production and release of platelet-activating factor (PAF); dissociation from degranulation and superoxide production in the human neutrophil.
Authors: Betz S J , Henson P M
Published: December 2022

The generation of human PAF was examined using purified neutrophils from normal and CGD donors. PAF release occurred in response to all of the neutrophil stimuli examined, including PMA and the calcium ionophore A23187, which initiate the relatively selective release of specific granule constituents. PAF release was dissociable from neutrophil degranulation by 1) the lack of correlation between PAF titers and extent of enzyme release for different stimuli, 2) the strict dependence of PAF release on the presence of extracellular Ca++, 3) the different kinetics for release of PAF and granule enzymes, and 4) the ability of neutrophils significantly depleted of azurophil and specific granule constituents to release normal levels of PAF when stimulated with opsonized zymosan. PAF release was also normal, if not elevated, in neutrophils from patients with chronic granulomatous disease, demonstrating that the formation and release of PAF does not depend upon an intact superoxide generating pathway.
The role of antigen-presenting cells in the IgE antibody response. I. The induction of high titer IgE antibody responses in IgE high-responder and low-responder mice by the administration of antigen-pulsed macrophages in the absence of adjuvants.
Authors: Kudo K , Sehon A H , Schwenk R J
Published: December 2022

The administration of 2 i.p. injections of 2 x 10(7) ovalbumin- (OA) pulsed, syngeneic, adherent, peritoneal exudate cells (OA-pulsed macrophages [M phi]) to (C57BL/6 x DBA/2)F1 (B6D2F1) mice promoted a persistent and high-titer anti-OA IgE response in these mice. Similarly, 2 i.p. injections of OA-pulsed DBA/2 parental M phi also induced the generation of an anti-OA IgE response in B6D2F1 mice; an identical procedure using OA-pulsed C57BL/6 parental M phi, on the other hand, elicited in most cases a very weak to negligible anti-OA IgE response. The administration of 3 i.p. injections of OA-pulsed syngeneic M phi to SJL mice also induced these "IgE nonresponder" mice to develop an anti-OA IgE response that was both boosterable and of moderate to high titer. The significance of these results with regard to the induction and regulation of the IgE antibody response is discussed.
Evolutionary relationship of thymopoietin to immunoglobulins and cellular recognition molecules.
Authors: Hahn G S , Hamburger R N
Published: December 2022

The sequence of thymopoietin, a thymic hormone composed of 49 amino acids, was compared to sequences of immunoglobulins and related cellular recognition molecules. Maximum homology was found between an active site of thymopoietin and homologous regions of IgG, IgE, beta 2-microglobulin, HLA-B7 and the Thy-1 antigen predicted to mediate immunologic activities, including Fc receptor binding. These results suggest that thymopoietin may be derived from approximately one half of the ancestral domain common to immunoglobulins and related immune system molecules and provide further support for a general theory that predicts the location of active sites in molecules of the immune system.
Murine C4-binding protein: a rapid purification method by affinity chromatography.
Authors: Kaidoh T , Natsuume-Sakai S , Takahashi M
Published: December 2022

A simple, 3-step method was described for purification of murine C4 binding protein (C4-bp), a recently recognized serum protein that functions as one of the regulatory proteins of the complement system. The method consists of 1) affinity chromatography using TNBS-BGG-conjugated Sepharose beads, 2) gel filtration on a Sepharose 6B column, and 3) heparin-Sepharose chromatography. By this method, milligram quantities of C4-bp can be easily purified by more than 500-fold from EDTA-serum of various mouse strains, and the whole purification process can be completed within 1 wk. The overall yield of C4-bp is about 15%. The C4-bp thus prepared is homogeneous as judged by SDS-polyacrylamide gel electrophoresis and immunelectrophoresis. The purified mouse C4-bp showed physicochemical properties very similar to those described for human C4-bp. Like human C4-bp, mouse C4-bp is composed of several apparently identical subunits of the m.w. of 80,000. However unlike the human counterpart, the subunits of mouse C4-bp are not linked by disulfide bonds but are connected by non-covalent forces that can be disrupted by SDS. The purified mouse C4-bp retained binding affinity for C4 and showed unaltered antigenicity. Immunization of rabbits with the purified mouse C4-bp resulted in the production of potent and monospecific antisera.
Peroxidase-mediated toxicity to schistosomula of Schistosoma mansoni.
Authors: Jong E C , Mahmoud A A , Klebanoff S J
Published: December 2022

Guinea pig eosinophil peroxidase (EPO) was capable of killing schistosomula of Schistosoma mansoni in vitro when combined with hydrogen peroxide and a halide. Killing was measured by 51Cr release, by microscopic evaluation of viability, and by reinfection experiments in mice. Parasite killing was dependent on each component of the EPO-H2O2-halide system, was completely inhibited by catalase and azide, and was partially inhibited by cyanide. The EPO-mediated system required 10(-4) M H2O2 and 10(-4) M iodide at pH 7.0, and the schistosomula were killed with exposure to this system of less than 30 min at 37 degrees C. At pH 6.0, the EPO-mediated system showed significant cidal activity with 10(-6) M iodide. Canine neutrophil peroxidase (myeloperoxidase [MPO]) was also able to kill schistosomula in vitro in the presence of 10(-4) M H2O2 and 10(-4) iodide at pH 7.0 and pH 6.0. Physiologic concentrations of chloride (0.1 M) could substitute for iodide at pH 7.0 and pH 6.0 as the halide cofactor; however, at pH 7.0, a higher concentration of enzyme was required. These findings with isolated enzyme systems are compatible with a role for peroxidase in the host defense against schistosomula.
Deletion of antigen-specific activity from leukocyte dialysates containing transfer factor by antigen-coated polystyrene.
Authors: Borkowsky W , Lawrence H S
Published: December 2022

We have reported finding antigen-specific activity in human leukocyte dialysates (DLE) containing TF in the leukocyte migration inhibition (LMI) assay. To analyze this activity further, we have used polystyrene bound to antibody or to antigen as immunoadsorbent for DLE before pulsing nonimmune cells in the LMI assay. Candida-(CAN) immune or diphtheria toxoid-(TOX) immune DLE were depleted of all antigen-specific activity after absorption with specific antigen but not affected by absorption with specific antibody, respectively, and depletion of activity with antigen was abrogated by coating bound antigen with specific antibody before absorption of DLE. CAN-immune, TOX-immune DLE was selectively depleted for either CAN activity or TOX activity after absorption with CAN- or TOX-coated polystryrene, respectively, retaining its CAN-activity when absorbed with TOX and conversely retaining its TOX activity when absorbed with CAN; thus the antigen-specific activity binds to related but not unrelated antigen. The polystyrene-bound antigen-specific activity could be recovered by treatment with 8 M urea. We interpret these findings to suggest that such antigen-specific activity may be either a dialysable fragment of a T cell antigen receptor site, or a portion of the V-region, or a unique Ir gene product that assists in antigen presentation to other T cells.
Cell cycle related heterogeneity of Ia antigen expression on a murine B lymphoma cell line:analysis by flow cytometry.
Authors: Lanier L L , Warner N L
Published: December 2022

In this investigation we have used quantitative flow cytometry to study the expression of I region antigens on an established B lymphoma cell line, WEHI-231. Although a majority of the WEHI-231 cells do not react with antisera against the Ia.7 (I-E/C) or Ia.8 (IaA) antigens, a distinct subpopulation of cells, comprising 20 to 30% of the total population, reacts strongly with these alloantisera. Several mechanisms were proposed to explain this intratumor Ia antigen heterogeneity: 1) the effect of volume (surface area) heterogeneity on antigen expression; 2) the existence of a stable variant of Ia+ cells in the cell line; 3) cell cycle regulation of Ia antigen expression. The first possibility was excluded on the basis of FCM analysis, which failed to detect any relationship between cell volume and fluorescence intensity of anti-Ia stained cells. Additionally, the rapid reappearance of Ia antigen heterogeneity within Ia- and Ia+ lines, sorted by the fluorescence-activated cell sorter, argued against the presence of a stable variant population of Ia+ cells. Rather, our data suggest that cell cycle related events are responsible for the Ia antigen heterogeneity. The Ia.7+ sorted cells were shown to be significantly enriched in the G0/G1 phase of the growth cycle. In contrast, it was the Ia.8- cells that were enriched in this phase of the cell cycle. These results suggest that the I-A and I-E/C region gene products are independently regulated in this cell line and imply that similar controls may possibly influence Ia antigen expression on normal B lymphocytes.
Activation of murine B lymphocytes. III. Stimulation of B lymphocyte clonal growth with lipopolysaccharide and dextran sulfate.
Authors: Wetzel G D , Kettman J R
Published: December 2022

Proliferation of single B cells was observed in response to the combination of LPS and DXS when spleen cells were placed into Terasaki plates at dilutions where the majority of wells containing cells contained one cell. Clones derived from a single cell exhibited varying morphologies and growth characteristics. Neither filler cells nor conditioned medium was required for these responses. Since isolated cells were stimulated, we conclude that B cells can be activated to clonal growth in the absence of accessory cells. Limiting dilution analysis showed that the frequency of cells responding to the combination of LPS + DXS was about 80% of the frequency of input B cells. When only LPS or DXS was present, the frequency of response was less than 25% and less than 5% of the input B cell frequency, respectively. This synergy in mitogenesis is consistent with previous kinetic and cytofluorometric analyses of mitogen-stimulated growth which have indicated that the combination of LPS + DXS removes requirements for cell interaction in growth induction and that B lymphocytes can be stimulated to growth directly.
Requirement of T cells for the development of spontaneous autoimmune thyroiditis in obese strain (OS) chickens.
Authors: de Carvalho L C , Wick G , Roitt I M
Published: December 2022

A combination of neonatal thymectomy and intensive treatment with a highly specific turkey anti-chicken T cell serum effectively abrogates the spontaneous development of thyroiditis and thyroglobulin autoantibodies in the Obese strain chicken. Thus, in addition to a restraining influence of suppressor T cells on the disease process indicated by earlier studies, it would appear that T cells also make a positive contribution to pathogenesis.
Antigen-presenting function of alveolar macrophages: uptake and presentation of Listeria monocytogenes.
Authors: Weinberg D S , Unanue E R
Published: December 2022

Mouse alveolar macrophages were characterized and compared to resident peritoneal macrophages for their ability to take up and present to immune T cells the bacteria Listeria monocytogenes. Both macrophage populations contained a similar proportion of Ia-positive macrophages (approximately 5%). However, alveolar macrophages showed a deficiency in the uptake of Listeria monocytogenes. Macrophage, antigen-presenting function was studied by measuring the proliferative response of Listeria-immune T cells to Listeria-pulsed macrophages. The alveolar macrophages were capable of presenting Listeria, although less effectively than the peritoneal macrophages. Listeria presentation by alveolar macrophages was dose dependent, antigen specific, and genetically restricted, and required the presence of Ia-positive macrophages. The differences in antigen-presenting function between alveolar and peritoneal macrophages appeared to be due solely to their differences in Listeria uptake. Thus, opsonizing Listeria resulted in marked enhancement of both Listeria uptake and presentation by alveolar macrophages. These findings demonstrate that alveolar macrophages possess I-region-dependent antigen-presenting function and emphasize the importance of bacterial binding by macrophages in generating effective immune stimulation.
Relationship of idiotypes of the anti-p-azophenylarsonate antibodies of A/J and BALB/c mice.
Authors: Brown A R , Lamoyi E , Nisonoff A
Published: December 2022

It has previously been shown that A/J anti-Ar antibodies contain 2 different families of cross-reactive idiotypes, referred to as the major and minor idiotypes populations. The present report shows that the minor A/J idiotype is related to a major idiotype of BALB/c anti-Ar antibodies. Anti-idiotype directed against the minor A/J idiotype binds 5 to 10% of A/J anti-Ar but an average of about 40% of BALB/c anti-Ar. This BALB/c population corresponds to the major BALB/c anti-Ar idiotype. For individual BALB/c anti-Ar preparations the maximum percentages of antibody bound by anti-id directed to A/J or BALB/c anti-Ar are very similar. Anti-id reactive with the minor A/J idiotypic population suppressed the formation of the BALB/c major idiotype when injected into BALB/c mice. Adsorption experiments showed that only about one-third of the minor A/J population is related to the BALB/c idiotype and that the expression of this idiotype is highly variable in individual A/J sera. Several types of evidence, obtained with hybridoma products expressing the major A/J idiotype, revealed no detectable relationship between the major A/J and BALB/c anti-Ar idiotypes.
Human lymphocyte markers defined by antibodies derived from somatic cell hybrids. IV. A monoclonal antibody reacting specifically with a subpopulation of human B lymphocytes.
Authors: Brooks D A , Beckman I G , Bradley J , McNamara P J , Thomas M E , Zola H
Published: December 2022

The technique of somatic cell hybridization has been used to produce a monoclonal antibody (designated FMC7) against the human B lymphoblastoid cell line HRIK. By indirect immunofluorescence FMC7 reacted with a total of 3 out of 10 B cell lines, but failed to bind T and Null cell lines. On normal peripheral blood, FMC7 bound between 3 and 6% of mononuclear cells. When normal peripheral blood mononuclear cells were fractionated, FMC7 reacted with only the B-enriched fraction, staining some but not all cells expressing SMIg. Double marker analysis indicated that the antigen detected by FMC7 is not identical with any of the conventional B cell markers, including surface membrane IgM, C3 receptors, Fc receptors, and the binding site for mouse erythrocytes. Another monoclonal antibody, FMC1, which reacts specifically with B lymphocytes, binds a separate antigenic determinant. Thus, FMC7 appears to recognize a previously undetected marker present specifically on a subpopulation of human B lymphocytes. FMC7 reacts with some but not all B cell leukemias and may have diagnostic applications in leukemia.
Oxidation of n-formyl methionyl chemotactic peptide by human neutrophils.
Authors: Tsan M F , Denison R C
Published: December 2022

Human neutrophils during phagocytosis oxidized the synthetic chemotactic peptide, n-formyl methionyl-leucyl-phenylalanine (n-FMLP), to its sulfoxide derivative (n-FMsLP). The oxidation of n-FMLP by phagocytosing neutrophils was inhibited by methionine, but not by methionine sulfoxide, leucine, or phenylalanine, confirming that it was the methionine moiety of n-FMLP that was oxidized. The oxidation of n-FMLP was also inhibited by myeloperoxidase inhibitors or catalase, but not by SOD or mannitol, suggesting the involvement of the myeloperoxidase system. Since n-FMsLP does not have chemotactic activity, the oxidation of n-FMLP by phagocytosing neutrophils may be one mechanism by which neutrophils modulate the inflammatory process.
Mouse c1q: light and electron microscopic immunohistochemical localization.
Authors: McManus L M , Nakane P K
Published: December 2022

The localization of mouse C1q in various mouse tissues was assessed by immunohistochemistry. In all mouse strains examined, C1q was associated with cells in small focal areas of lymph nodes, Peyer's patches, and spleens often near germinal centers. Ultrastructural studies of these foci demonstrated that C1q was present in the endoplasmic reticulum of mononucleated cells that had an extensive cytoplasmic network. Occasionally, small deposits of C1q were observed in the perinuclear space of mononucleated cells that had scanty cytoplasm with few organelles. Extracellular C1q was found at the surface of interdigitating cell processes in these lymphatic foci. In addition to the presence of C1q within lympho-reticular tissues, C1q frequently was detected in renal glomeruli but not in urinary tract epithelium or intestinal epithelium of adult mice; in contrast, C1q was localized in the intestinal epithelium of neonatal mice. C1q was not detected in tissue fibroblasts nor in cultured fibroblasts; however, a subpopulation of mouse adherent peritoneal cells maintained in vitro did contain C1q. The results of these studies provide new information regarding the distribution and, thus, the possible sites of C1q biosynthesis in normal mouse tissues.
Antigens on human monocytes identified by monoclonal antibodies.
Authors: Todd R F , Nadler L M , Schlossman S F
Published: December 2022

Two antigens (Mo1 and Mo2) present on human peripheral blood monocytes have been defined by lytic IgM monoclonal antibodies. Both antigens are present on greater than 70% of adherent mononuclear cells (predominantly monocytes). Mo1 is expressed by monocytes, granulocytes, and Null cells, but is absent from T and B lymphocytes. Mo2, on the other hand, appears specific for peripheral blood monocytes. Neither antigen is present on Ia-positive B cell lines or on tumor cells from patients with B cell lymphoproliferative malignancies, further excluding the possibility that Mo1 and Mo2 are Ia antigens. Mo1 and Mo2 are, however, present on a significant number of blast cells from patients with monocytic leukemia (both myelomonocytic and pure monocytic variants), but relatively infrequently expressed by cells from patients with acute granulocytic leukemia. These results indicate that Mo1 and Mo2 are unique antigens that may represent distinct stages of late monocyte-granulocyte differentiation.
Genetics of natural antitumor antibody production: antibodies to MHC-linked determinants detected in the serum of unstimulated mice.
Authors: Wolosin L B , Greenberg A H
Published: December 2022

The genetics of natural antitumor antibodies was studied in several murine strains with 4 target tumors. We found that the levels of NAb detected depended on the strain-tumor combination and that high levels of NAb were inherited recessively. These observations suggested that NAb specificities are selectively regulated. Studies of backcross progeny and of H-2 congenic mice provided evidence for the genetic linkage between NAb levels and the MHC. From studies in which it was demonstrated that allogeneic NAb were absorbed with splenocytes bearing the haplotype of the target cell but not by other splenocytes, it was concluded that allo-NAb were recognizing H-2 antigenic determinants, or an antigen(s) whose expression is closely linked to the MHC. It is suggested, therefore, that low levels of NAb against the DBA/2 tumors studied in mice of the d haplotype were due to self tolerance.
The complement system in rainbow trout (Salmo gairdneri). II. Purification and characterization of the fifth component (C5).
Authors: Nonaka M , Natsuume-Sakai S , Takahashi M
Published: December 2022

The fifth component of rainbow trout complement was purified to homogeneity using a 4-step purification procedure: 1) 5 to 15% polyethylene glycol precipitation; 2) DEAE-Sepharose column chromatography; 3) gel filtration on Sephadex G-200; and 4) CM-Sepharose column chromatography. A 175-fold purification was attained with 20 to 30% yield of C5 antigen and hemolytic activity. The rainbow trout C5 thus purified was homogeneous as judged by SDS-polyacrylamide gel electrophoresis and immunoelectrophoresis. Rainbow trout C5 was composed of 2 polypeptide chains with m.w. of 133,000 daltons and 86,000 daltons linked by disulfide bonds. The highly purified C5 retained its functional activity. It fully reconstituted the hemolytic titer to C5-depleted rainbow trout serum. Upon activation, this protein was incorporated into a macromolecular complex that closely resembles a membrane attack complex (MAC) of human and guinea pig complement. On the basis of physico-chemical and functional characteristics, we identified this protein as the rainbow trout counterpart of mammalian C5. The identification of C5 in rainbow trout serum strengthened our previous conclusion that the complement system is in a highly developed state already at the phylogenetic level of teleost fish.
Platelet-serotonin release by C3a and C5a: two independent pathways of activation.
Authors: Meuer S , Ecker U , Hadding U , Bitter-Suermann D
Published: December 2022

C3a and C5a were investigated for their ability to induce secretion of serotonin from platelets in a homologous guinea pig system. Platelets respond to either anaphylatoxin with a dose-dependent release that does not exceed a plateau at the 70% level. On a molar basis. C5a is about 50-fold more active than the C3 fragment. The C5a effects in the platelet system can be clearly distinguished from the activity of C3a and vice versa by a phenomenon of specific desensitization of the platelets to either stimulus. Our observations lead to the postulation of distinct receptors for C3a and C5a on guinea pig platelets as well as 2 independent pathways of platelet activation, which both lead to a specific release.
Stimulation of nonlymphoid mesenchymal cell proliferation by a macrophage-derived growth factor.
Authors: Martin B M , Gimbrone M A , Unanue E R , Cotran R S
Published: December 2022

Cultured mouse peritoneal macrophages secrete a growth-promoting activity that stimulates 3 types of nonlymphoid mesenchymal cells in vitro: fibroblasts, vascular smooth muscle, and vascular endothelium. Production of this macrophage-derived growth factor (MDGF) is directly related to the number of viable macrophages and their time in culture, and is independent of platelet- or plasma-derived serum growth factors. Treatment of cultured macrophages with latex, bacterial lipopolysaccharide, or phorbol myristate acetate results in increased growth factor activity. Preliminary biochemical characterization of MDGF indicates that it is a heat labile (100 degrees C, 2 min), non-dialyzable protein, which contains at least 1 essential disulfide bond. Growth-promoting activity is not adsorbed by CM-Sephadex chromatography, under conditions that effectively remove platelet-derived growth factor(s). Serine protease activity is not required for the action of MDGF. Secretion of macrophage-derived growth factor may be relevant to the function of mononuclear phagocytes in several pathologic processes, including the neovascularization and fibroplasia of wound healing, smooth muscle hyperplasia in atherosclerosis, and proliferative glomerulonephritis.
The immunologic response in mice unresponsive to experimental allergic encephalomyelitis.
Authors: Lando Z , Teitelbaum D , Arnon R
Published: December 2022

The suppressor cells that are involved in antigen-induced protection against EAE in mice were investigated with respect to their effect on the immune response. The cellular immune response to the basic encephalitogenic protein (BE) and to PPD were studied in mice with either actively induced or adoptively transferred unresponsiveness to EAE. The results demonstrate that the DTH response to BE, as assayed in the radiometric ear skin test, was suppressed in mice protected against EAE. Moreover, the passive transfer of DTH response to BE by effector lymphocytes was also inhibited by the preinjection of suppressor cells. On the other hand, the suppressor cells did not affect the response to PPD in all these experiments. The results indicate that suppressor cells that mediate unresponsiveness to EAE regulate also the cellular immune response to BE in a specific manner. These suppressor cells are probably active both at the induction and the effector phase of the immune response.
Inhibition of human natural cytotoxicity by macromolecular antiproteases.
Authors: Hudig D , Haverty T , Fulcher C , Redelman D , Mendelsohn J
Published: December 2022

Human natural cell-mediated cytotoxicity is inhibited by macromolecular protease inhibitors. Human plasma alpha 1 antiproteases are more effective than the plant antiproteases lima bean trypsin inhibitor and soybean trypsin inhibitor for reduction of cytotoxicity to the "slow" targets T24 human bladder carcinoma and NKI-1 melanoma. This inhibition of natural cytotoxicity is more readily demonstrable in serum-free medium containing crystalline bovine serum albumin than in medium containing fetal calf serum. Although electrophoretically homogeneous plasma alpha 1 antitrypsin inhibits natural cytotoxicity, partially purified alpha 1 antitrypsin preparations that contain several apha 1 proteins are more inhibitory at equivalent trypsin inhibitory capacities. Partially purified alpha 1 antichymotrypsin with no antitrypsin activity is an extremely potent inhibitor. Thus, it seems likely that several of the plasma antiproteases, including alpha 1 antitrypsin and alpha 1 antichymotrypsin, are capable of influencing natural cytotoxicity. These data indicate that serine-dependent proteases hae a critical role in triggering and/or effecting cell-mediated cytolysis. Furthermore, since alpha 1 antichymotrypsin and alpha 1 antitrypsin are acute phase proteins, the increase in plasma concentration or turnover rates of the proteins could influence natural killer cell activity in vivo.
Immunosuppression in a murine B cell leukemia (BCL1): role of an adherent cell in the suppression of primary in vitro antibody responses.
Authors: Anderson S A , Isakson P C , Puré E , Muirhead M , Uhr J W , Vitetta E S
Published: December 2022

The ability of lymph node cells from mice bearing the BCL1 tumor to respond in vitro to mitogens, allogeneic cells, and both TI and TD antigens was investigated. The lymph nodes of such mice are not invaded with tumor cells and contain normal numbers of T and B cells. Nevertheless, at the peak of tumor burden in the spleen and blood (approximately 8 to 12 wk after injection with tumor cells), the lymph node cells from the tumor-bearing mice display markedly decreased responsiveness both to allogeneic cells and to antigens. In addition, small numbers of lymph node cells from the tumor-bearing mice suppress primary antibody responses of normal lymph node cells. This nonspecific suppression of antibody responses is mediated by a G-10 Sephadex adherent, non-T, non-B cell present in the nodes of the tumor-bearing mice. Since the BCL1 tumor model is in many respects similar to the prolymphocytic type of human chronic lymphocytic leukemia, the present results may be helpful in elucidating the mechanisms underlying the in vivo immunosuppression associated with lymphocytic neoplasms in humans.
Antibody to staphylococcal enterotoxin A-induced human immune interferon (IFN gamma).
Authors: Langford M P , Weigent D A , Georgiades J A , Johnson H M , Stanton G J
Published: December 2022

Antiserum to human gamma interferon (IFN gamma) was produced in rabbits immunized with partially purified (10(4.8) to 10(6.2) antiviral U/mg protein) staphylococcal enterotoxin A-induced IFN gamma. Staphylococcal enterotoxins, phytohemagglutinin M, concanavalin A, and pokeweed mitogen-induced antiviral activity in human leukocyte cultures was neutralized to undetectable levels by the antiserum. However, human leukocyte interferon (IFN alpha), human fibroblast interferon (IFN beta), and mouse interferons were not neutralized by the antiserum. After determining the antiserum was specific for IFN gamma and did not neutralize other known types of interferon, it was used with antibody to human IFN alpha to demonstrate the type(s) of interferon stimulated by some new inducers and antigens. Galactose oxidase- and calcium ionophore-induced interferons were neutralized to undetectable levels by the antiserum to IFN gamma. Interferon produced in leukocyte cultures from tuberculin-negative individuals stimulated with tuberculin-purified protein derivative or old tuberculin was IFN alpha, whereas interferon from tuberculin-positive individuals was a combination of alpha and gamma IFN. In addition, the antiserum neutralized the anticellular and natural killer cell enhancement activities of IFN gamma preparations. The specificity of this antiserum for IFN gamma indicates that it is an additional, powerful tool for identifying and classifying known and new interferons produced in vitro or in vivo and for investigating the role(s) of IFN gamma during the course of infectious, neoplastic, and autoimmune diseases.
Evidence for linkage of murine beta 2-microglobulin to H-3 and Ly-4.
Authors: Goding J W
Published: December 2022

Murine beta 2-microglobulin exists in 2 electrophoretically distinct forms; C57BL/6 mice possess the basic allele whereas BALB/c, CBA, AKR, and NZB possess the acidic allele. Mice heterozygous for beta 2-microglobulin express both alleles. Analysis of recombinant inbred mice suggests linkage of beta 2-microglobulin to H-2 or H-3. B10.C (28NX) mice (which possess the H-3c allele of BALB/c on a C57BL/10 background) possess the acid allele. Taken together, these results are consistent with the beta 2-microglobulin gene lying on chromosome 2, and being linked to H-3 and Ly-4.
Genetic control of experimental autoimmune myasthenia gravis in mice. II. Lymphocyte proliferative response to acetylcholine receptor is dependent on Lyt-1+23- cells.
Authors: Christadoss P , Krco C J , Lennon V A , David C S
Published: December 2022

The proliferative response of regional lymph node lymphocytes to Torpedo acetylcholine receptor (TAR) is under H-2 linked Ir gene control. In high responder B6 (H-2b) congenic mice, lymphocytes that proliferate in vitro in response to TAR are dependent on T cells of a subpopulation expressing the phenotype associated with helper functions, Lyt-1+23-.
Amphotericin B-induced resistance to Schistosoma mansoni.
Authors: Olds G R , Stewart S J , Ellner J J
Published: December 2022

Amphotericin B (AmB) increases host resistance against several infectious agents and tumors. We evaluated its effect on infections with the helminth Schistosoma mansoni. A single dose of 500 microgram i.p. or 25 microgram i.v. increased resistance in mice to a challenge with 500 or 100 S. mansoni cercariae. Schistosomula recovery from the lungs, 5 days after challenge, was reduced 33 to 40%. Adult worm recovery 8 wk after infection was reduced 36 to 43%, AmB was effective in protecting mice when given from 9 days before until the day of cercarial challenge but was ineffective 2 wk before or at all intervals after S. mansoni infection. To examine the mechanism of this resistance, we obtained peritoneal exudate cells (PEC) from animals treated with AmB and assessed their ability to kill schistosomula, the migrating larval stage of the parasite. Killing by adherent PEC 1 or 2 days after AmB treatment was the same as that of resident macrophages from untreated animals. Adherent PEC from animals 3 to 7 days after AmB treatment showed enhanced killing of schistosomula (38.0 plus or minus 3.0% at day 4, which exceeded control of 8.1 plus or minus 4.0%, p less than 0.01). These PEC also displayed increased killing of Staphylococcus aureus. When AmB was added to cultures of resident peritoneal adherent cells from untreated mice at 0.5 microgram/ml to 2.0 microgram/ml (concentrations not toxic to the organism), schistosomula killing was increased 1- to 6- fold. These findings demonstrate activation of murine macrophages by AmB in vitro and in vivo, which results in greater killing of this multicellular parasite and potentially contributes to enhanced resistance to infection.
Formation of IgE binding factors by human T lymphocytes.
Authors: Ishizaka K , Sandberg K
Published: December 2022

Peripheral blood mononuclear cells from ragweed-sensitive individuals formed soluble factors that inhibited rosette formation of Fc epsilon receptor (+) cells with IgE-coated ox erythrocytes when the cells were incubated with ragweed antigen E and human IgE. Either antigen E alone or IgE alone failed to induce the formation of the rosette inhibiting factors. Two-way mixed lymphocyte culture from 2 normal individuals followed by incubation of the activated lymphocytes with IgE induced the formation of the rosette-inhibiting factor. Normal human mononuclear cells cultured in the presence of T cell growth factor (TCGF) formed the soluble factor when they were incubated with IgE. The rosette-inhibiting factor in culture filtrates was specifically absorbed with IgE-coupled Sepharose and was recovered from the beads by elution at acid pH, indicating that the soluble factors have affinity for IgE. Because the lymphocytes cultured with TCGF were mostly T cells and contained neither B cells nor monocytes, it appears that the IgE-binding factors are derived from T cells.
In vitro induction of HLA-restricted cytotoxic T lymphocytes against autologous Epstein-Barr Virus transformed B lymphoblastoid cell line.
Authors: Fukukawa T , Hirano T , Sakaguchi N , Teranishi T , Tsuyuguchi I , Nagao N , Naito N , Yoshimura K , Okubo Y , Tohda H , Oikawa A
Published: December 2022

Cytotoxic T lymphocytes (CTL) against autologous EBV-transformed B lymphoblastoid cell line (LCL) were induced in vitro by culturing peripheral blood lymphocytes (PBL) of healthy donors together with mitomycin C-treated autologous LCL for 6 days. The cytotoxic cells developed only from the E-rosette-positive fraction but not from the negative fraction of PBL. These CTL killed autologous LCL but not PWM-stimulated autologous PBL. In addition, the CTL killed allogeneic LCL when at least 1 of the HLA-A antigens was identical with that of the LCL of CTL donor. However, identity of HLA-B and HLA-C antigens was not enough for a significant killing of allogeneic LCL. The specificity of the CTL was also confirmed by a cold target inhibition test. These results indicated that the CTL induced specifically recognized EBV-transformed cells with HLA restriction.
Spatially distinct allodeterminants of the H-2Kk molecule as detected by monoclonal anti-H-2 antibodies.
Authors: Ozato K , Henkart P , Jensen C , Sachs D H
Published: December 2022

In an attempt to delineate spatial relationships between various allodeterminants of cell surface MHC antigens, competitive binding studies were performed using 4 different monoclonal antibodies, each of which reacted with the H-2Kk antigen but with different serologic specificities. Competition was studied by examining the effect of unlabeled antibodies on the binding of each 125I-labeled antibody to spleen cells of the H-2a haplotype. Mutual inhibition was observed between 2 of the antibodies, and a 3rd antibody of lower affinity was inhibited by the first 2 antibodies but did not itself inhibit the binding of these antibodies. The 4th antibody did not block the binding of the other 3 labeled antibodies, and binding of this 4th labeled antibody was only partially inhibitable by the other 3 antibodies. These results indicate the presence of at least 2 spatially distinct allodeterminants on H-2Kk molecules expressed on the cell surface.
Induction of balanced immunoglobulin chain synthesis in free light chain-producing lymphocytes by mitogen stimulation.
Authors: Hannam-Harris A C , Smith J L
Published: December 2022

Neoplastic cells from 2 cases of CLL synthesized and secreted excess free Ig light chain in culture, confirmed by precipitation with anti-idiotypic antibody. Small and medium sized normal human spleen cell subpopulations, staining predominantly for surface IgM and D, also synthesized and secreted excess free light chain. PWM stimulation induced balanced synthesis of heavy and light chains in CLL and normal spleen subpopulations after 6 days in culture, accompanied in spleen but not CLL by the appearance of mature plasma cells. These data demonstrate that normal cell counterparts of neoplastic lymphoid synthesis patterns can be identified in spleen. Furthermore, the synthesis pattern alteration after PWM stimulation suggests a relationship between free light chain synthesis and B cell immaturity. The failure of CLL cells to develop into detectable plasma cells suggests a restricted maturation response to mitogen compared with normal spleen.
Activation of mouse macrophages for tumor cell killing. I. Quantitative analysis of interactions between lymphokine and lipopolysaccharide.
Authors: Pace J L , Russell S W
Published: December 2022

Lymphokine-rich supernatants from concanavalin A-stimulated spleen cell cultures failed to activate mouse peritoneal macrophages for tumor cell killing, providing that the assay system was free of detectable (less than 0.125 ng/ml) endotoxin. Instead, increasing amounts of lymphokine progressively increased the sensitivity of macrophages to activation by purified bacterial lipopolysaccharide (LPS). Conversely, the effect of minute amounts of lymphokine could be detected in the presence of relatively high (though nonactivating) concentrations of LPS. The latter observation was exploited to develop a highly sensitive, quantitative assay for lymphokine. In this assay, serially diluted supernatants were tested on macrophage monolayers in the presence of a constant concentration (3 ng/ml) of LPS. Under these conditions, the lymphokine dose-response curve was sigmoidal and therefore suitable for conversion to a linear plot using the logarithmic transformation of the von Krogh equation. Activity could be expressed quantitatively and reproducibly in terms of units of activity. By facilitating purification the assay should contribute to the development of a more precise biochemical understanding of the role of lymphokine in macrophage activation for tumor cell killing.
Relationship between epidermal Langerhans cell density ATPase activity and the induction of contact hypersensitivity.
Authors: Lynch D H , Gurish M F , Daynes R A
Published: December 2022

Langerhans cells have been implicated as playing a crucial role as antigen-processing cells in the induction of positive immune responses to antigens presented through the skin. We have investigated the effects of carcinogenic doses of UVB-irradiation, psoralen plus UVA light (PUVA), PABA containing sunscreen preparations, and topically applied corticosteroids on both Langerhans cell densities and immunologic responsiveness to contact sensitizers applied to the treated site. The data presented demonstrate that UV-irradiation of skin or topical application of corticosteroids can create a local milieu in which DNFB cannot function as an effective stimulator of contact hypersensitivity. Further, we have shown that the effect induced by UV light is reversible, does not appear to be related to the numerous tissue destructive effects of UVB-irradiation, and that the correlation with the density of ATPase-positive cells is not absolute.
Use of a synthetic hapten in the demonstration of the Thomsen-Friedenreich (T) antigen on neuraminidase-treated human red blood cells and lymphocytes.
Authors: Bray J , Lemieux R U , McPherson T A
Published: December 2022

Using an artificial T hapten, we have confirmed that human sera contain agglutinins for neuraminidase-treated red blood cells (N'RBC), specific for the disaccharide beta DGal(1 leads to 3)alpha DGalNAc. Further, we have shown that these agglutinins are antibodies largely of the IgM subclass that bind equally to neuraminidase-treated lymphocytes (N'lymphocytes). The anti-T antibody in human serum is cytotoxic for N'RBC in complement fixation assays. The synthetic hapten has biologic activity as shown in inhibition experiments and by the specificity of a rabbit antibody raised to the hapten for the naturally occurring antigen on N'RBC and N'lymphocytes. An immunoadsorbent prepared from the hapten was used to obtain biologically active antibodies from human serum with specificity for the naturally occurring antigen.
Mitogenic response of human peripheral blood lymphocytes to a purified C. albicans polysaccharide fraction: lack of helper activities is responsible for the in vitro unresponsiveness to a second antigenic challenge.
Authors: Piccolella E , Lombardi G , Morelli R
Published: December 2022

Human peripheral blood lymphocytes primed with MPPS (a polysaccharide fraction extracted from C. albicans) were unable to respond to a second challenge of the same antigen. The proliferative response of these lymphocytes was restored by both mitomycin C-treated fresh autologous lymphocytes and by helper factors. Removal of Ia+ cells from fresh lymphocytes abolished the helper effect. On the other hand, when primed lymphocytes were depleted of Ia+ cells, the helper factor-responding cells were eliminated, whereas Ia- cells maintained the capacity to respond to fresh autologous lymphocytes. A model for cell-cell cooperation involved in the regulation of the immune response to this antigen is proposed.
Regulation of T cell differentiation: in vitro induction of 20 alpha-hydroxysteroid dehydrogenase in splenic lymphocytes from athymic mice by a unique lymphokine.
Authors: Ihle J N , Pepersack L , Rebar L
Published: December 2022

The enzyme 20 alpha-hydroxysteroid dehydrogenase (20 alpha SDH) has previously been shown to be a specific enzyme marker of mature T cells. In vivo, the expression of 20 alpha SDH is thymus dependent, in that splenic lymphocytes from athymic mice have only low levels of activity, although the levels of enzyme activity increase gradually with age. In vitro, 20 alpha SDH can be induced in splenic lymphocytes from nu/nu mice by conditioned media from mitogen- or alloantigen-stimulated normal lymphocytes. Induction is rapid in vitro. Beginning after a lag period of approximately 6 hr, enzyme activity increases linearly for approximately 20 to 30 hr resulting in a 5- to 10-fold increase in activity. Induction is blocked by mitomycin C, suggesting a requirement for cell proliferation. The phenotype of both the precursor and the induced lymphocyte populations is Thy 1.2-, Lyt 1-, 2-, suggesting that induction of 20 alpha SDH expression is an early step in T cell differentiation. The factor responsible for 20 alpha SDH induction has been partially purified and is distinct from other known lymphokines in both its biochemical and functional properties. The term interleukin 3 is proposed for this factor.
H-2 negative teratocarcinoma cells become H-2 positive when passaged in genetically resistant host mice.
Authors: Ostrand-Rosenberg S , Cohan V L
Published: December 2022

The murine 402AX teratocarcinoma is an H-2 negative, nullipotent stem cell tumor of testicular origin. Previous studies have demonstrated that host strain resistance and susceptibility to this tumor are under the control of 2 genes, one of which is closely linked to the mouse major histocompatibility complex. Earlier studies determined the lack of antigenic modulation and the absence of H-2 antigens on 402AX cells passaged in vitro or in genetically susceptible hosts. The present studies demonstrate that when passaged in genetically resistant host mice [C57BL/10, B10.SM, and B10.129(6M)], the H-2 negative 402AX cells modulate to become positive for H-2b antigens, as detected by indirect immunofluorescence, microcytotoxicity, and quantitative absorption. Two to 4 days of in vivo growth in resistant hosts is necessary for H-2b antigens to be expressed. H-2 positive tumor cells removed from resistant hosts and placed in culture become H-2 antigen negative within 1 to 4 hr in vitro. H-2 antigen turn-on on the teratocarcinoma cells is specific for the H-2 haplotype of the tumor cell origin (129, H-2b); alien H-2 antigens are not expressed. The observation that only teratocarcinoma cells growing in genetically resistant hosts turn-on for H-2 antigens suggests that major histocompatibility antigens on target cells are required for an efficient host cell-mediated immune response against tumor cells.
Antigenic characterization of a T-CLL with heteroantisera and monoclonal antibodies: evidence for the T cell lineage of an Ia-positive, Fc-IgG--positive, suppressor-cell subpopulation.
Authors: Strong D M , Pandolfi F , Slease R B , Budd J E , Woody J N
Published: December 2022

In a previous report, peripheral blood mononuclear T cells from a patient with T-chronic lymphocytic leukemia (T-CLL) were shown to bear receptors for the Fc portion of IgG (T gamma). Moreover, the ability of these cells to rosette with sheep erythrocytes was strongly inhibited by a preincubation of the cells with theophylline. These data indicated that they represent a highly purified subpopulation of Fc-IgG receptor-positive, low-affinity rosetting cells with in vitro suppressor activity on lectin-induced proliferation of normal lymphocytes. They also were reactive in antibody-dependent cell-mediated cytotoxicity but had no reactivity in natural killer cell assays. These cells were studied in this report with several heteroantisera and monoclonal antibodies. Results indicate that these T-CLL cells express a T cell antigenic pattern (OKT-3+) and the majority are Ia positive. They also react with the OKT-8 reagent (a reagent detecting the subset of T cells that contains the cytotoxic/suppressor cells), whereas they are negative with OKT-4 (which reacts with the subset of T cells that contains helper cells) and OKT-6 (thymocyte) antibodies. Heteroantisera also support the results obtained with monoclonal reagents. Despite some recent evidence showing that a high percentage of T gamma cells may belong to the monocyte-myeloid lineage, these T-CLL cells were negative with OKM-1, a monoclonal antibody reported to detect a monomyeloid antigen. These results suggest that a distinct subpopulation of suppressor T cells can be identified by membrane-marker phenotyping.
Gluten-sensitive enteropathy. I. The T-dependent anti-A-gliadin antibody response maps to the murine major histocompatibility locus.
Authors: Trefts P E , Kagnoff M F
Published: December 2022

We examined the genetic control of the murine humoral immune response to purified A-gliadin, a protein derived from wheat gluten, which is known to cause small intestinal disease in susceptible individuals. Studies with congenic and noncongenic inbred strains of mice revealed that the T-dependent humoral immune response to A-gliadin is under the control of genes mapping to the mouse major histocompatibility complex (MHC). These findings in mice establish a clear linkage between the MHC and the regulation of the immune response to a protein capable of causing human disease.
The cell-mediated lympholysis-inducing capacity of highly purified human monocytes and T lymphocytes in primary and secondary mixed leukocyte cultures.
Authors: Spits H , de Vries J E , Terhorst C
Published: December 2022

In this study the capacity of T cells and monocytes to induce cell-mediated lympholysis (CML) in primary and secondary MLC was investigated. The T lymphocytes were enriched by rosetting with sheep red blood cells (E) and further purified by sedimentation at unit gravity, which completely removed the contaminating monocytes. In addition, a highly purified monocyte population was obtained by 1 X G sedimentation of the non-E rosette-forming cells. These purified T cells have a poor CML-inducing capacity in primary and secondary MLC. In contrast, monocytes were very effective in inducing CML in both primary and secondary MLC. Induction of CML by monocytes in primary MLC was inhibited by heterologous anti-Ia-like antisera, indicating that the induction of CML by monocytes was related to the presence of HLA-DR (Ia-like) antigens on these cells.