bluuebunny/crossref_metadata_2025_split huggingface dataset:
Desensitization of acute inflammatory lesions to chemotaxins and endotoxin.
Authors: Colditz I G , Movat H Z 
Published: December 2022

Abstract
Desensitization of the neutrophil inflammatory response to intracutaneous injection of chemotaxins and endotoxin was studied in rabbits. When restimulated 6 hr later with the same agent, inflammatory lesions initiated with platelet-activating factor (PAF), leukotriene B4 (LTB4), or endotoxin supported a diminished influx of neutrophils compared with responses in normal skin. In contrast, repeated stimulation of lesions with alpha-casein failed to lead to desensitization. The specificity of desensitization was investigated, and it was found that lesions initiated with formylmethionyl-leucyl-phenylalanine (FMLP) supported a normal response when restimulated with PAF, alpha-casein, or endotoxin. Initiation of lesions with LTB4, however, diminished the subsequent response to zymosan-activated plasma and PAF, but not endotoxin, alpha-casein, or FMLP. This result indicates that LTB4 is not a final common mediator of neutrophil infiltration of acute inflammatory lesions. Desensitization was detected irrespective of the concentration of chemotaxin used to investigate the response. Repeated stimulation of lesions with FMLP abolished the accumulation of neutrophils after the final stimulus, indicating that complete desensitization can occur and the presence of a chemotaxin within an inflammatory lesion is not sufficient stimulus for neutrophil infiltration of the site to proceed. Lesions initiated with endotoxin supported comparable responses when restimulated with a mixture of FMLP and endotoxin or FMLP alone, despite 93% inhibition of the response to restimulation with endotoxin alone. This indicates that a cell-directed inhibitor of neutrophil migration, such as lipomodulin or neutrophil-immobilizing factor, does not produce the diminished responses in desensitized lesions. It is proposed that desensitization occurs due to down-regulation of a receptor-coupled pathway that permits or facilitates neutrophil extravasation in acute inflammatory lesions. The chemotaxin receptors regulating neutrophil extravasation are probably located on endothelial cells of post-capillary venules.
Stimulation of anti-influenza cytolytic T lymphocytes by a synthetic peptide of the influenza hemagglutinin can be modulated by at least three independent helper factors.
Authors: Wabuke-Bunoti M A , Taku A , Garman R , Fan D P 
Published: December 2022

Abstract
Secondary murine anti-influenza cytolytic T lymphocytes (CTL) could be induced in vitro by the chemically synthesized peptide HA1(181-204), corresponding to amino acids 181-204 of the hemagglutinin molecule of influenza strain A/Japan/305/57. This stimulation required the addition of exogenous helper factors, termed CHFP, which could be obtained from supernatant fluids of the WEHI-3 cell line or spleen cells stimulated by either concanavalin A or Sendai virus. Because the activities from these three sources could reflect different molecules, they were referred to as CHFPW, CHFPC, and CHFPS, respectively. When CHFPS was fractionated by using reverse-phase high performance liquid chromatography (HPLC), the CHFP activity was found to elute at two hydrophobicities. The more hydrophilic factor(s) was designated CHFPS1, while the more hydrophobic factor(s) was called CHFPS2. Similarly, CHFPW could be separated into more hydrophilic (CHFPW1) and more hydrophobic (CHFPW2) molecules. In contrast, CHFPC molecules eluted at only one hydrophobicity (CHFPC1). Based on HPLC characteristics, CHFPS1, CHFPW1, and CHFPC1 all could reflect the same molecule. That molecule could be interleukin 3 (IL 3), because IL 3, purified to homogeneity, was also found to function in the CHFP assay. In contrast, CHFPW2 and CHFPS2 had different hydrophobicities. Therefore, a possibility exists that there are a minimum number of three factors functional in the CHFP assay: IL 3, CHFPW2, and CHFPS2. Based on HPLC separations, CHFPS2 represents a molecule distinct from biochemically characterized cytokines implicated previously in the generation of CTL:CHF, CSF, interferon, and interleukins 1, 2, and 3. The killer cells stimulated are both virus-specific and H-2-restricted as is characteristic of CTL.
A human monoclonal antibody to cytomegalovirus (CMV).
Authors: Emanuel D , Gold J , Colacino J , Lopez C , Hammerling U 
Published: December 2022

Abstract
We report the development of a human monoclonal antibody to cytomegalovirus (CMV) produced from a human X human hybridoma. This hybrid was developed by fusion of an EBV-transformed cell line making antibody to CMV and a human lymphoblastoid cell line WI-L2. The antibody is directed to a CMV-specific antigen primarily in the nucleus of CMV-infected human fibroblasts. It cross-reacts with at least 10 different strains of CMV and may provide a method for the rapid in vitro diagnosis of CMV infections. The production of CMV-specific human man monoclonal antibodies from human-human hybridomas for future therapeutic use is now technically feasible with this specific method of production.
Characterization of mononuclear phagocytes in schistosomal egg granulomas of athymic mice.
Authors: Stadecker M J , Ebner S A 
Published: December 2022

Abstract
Macrophages from schistosomal egg granulomas of athymic mice (nu/nu GM) and their euthymic littermates (nu/+ GM) were analyzed phenotypically for the expression of antigens encoded by the I-A subregion of the major histocompatibility complex and for their ability to perform as antigen-presenting cells. Only 11 to 15% of nu/nu GM expressed I-A antigens as compared to 61.5 to 75% of nu/+ GM. Although both populations of cells appeared to be equally effective as antigen-presenting cells appropriately sensitized lymphocytes in the presence of specific antigens--soluble schistosomal egg antigen (SEA) and human gamma-globulin (HGG)--only nu/nu GM, but not nu/+ GM, were found to stimulate I-A-restricted proliferation of schistosome-sensitized T cell populations in the absence of SEA added in vitro. Furthermore, nu/nu GM but not nu/+ GM were shown to exhibit significant proliferative capacity in vitro, but this phenomenon could not account for the observed difference in SEA-independent T cell stimulation. Finally, culture supernatants from nu/nu GM displayed significant thymocyte-stimulating activity, consistent with interleukin 1, which was not observed in nu/+ GM. These findings point to significant differences between nu/nu GM and nu/+ GM, which may be part of an adaptive mechanism of granulomatous reactivity in the absence of a competent T cell system.
Immunoradiometric assay for detection of filarial antigens in human serum.
Authors: Hamilton R G , Hussain R , Ottesen E A 
Published: December 2022

Abstract
The immunoradiometric assay (IRMA) for detection of filarial antigens in the serum of patients infected with Brugia malayi (Bm) or the closely related filarial parasite Wuchereria bancrofti (Wb) was investigated, and its performance and clinical utility were examined. Reference sera prepared by the addition of crude Bm antigen (BmA) to negative control human sera provided a reproducible reference curve. The IRMA displayed acceptable precision and reproducibility. Agreement between dilutions (parallelism) was good in sera without specific antibody, but the presence of even modest levels of antibody resulted in nonparallelism in about one-half of the tested sera from endemic areas. Significant reduction in detectable BmA occurred when low levels of specific antibody (less than 1 microgram/ml) were added to BmA containing sera. Thus, antibody interference limited absolute quantitation of antigen in the IRMA. Results were therefore expressed in a semi-quantitative manner by using the mean + 3 SD of the binding of nonexposed human sera as the positive threshold. The frequency of reliable filarial antigen detection in individuals from the Wb endemic areas of India and the South Pacific was the following: microfilaremia, 15 out of 15; elephantiasis, 2 out of 18; tropical pulmonary eosinophilia, 2 out 8. These findings show clearly that a two-site IRMA can effectively detect circulating antigen (and thus be diagnostic of infection) in a great many patients with filariasis, but to enhance the sensitivity of the assay to the point where all patients can be diagnosed, a number of suggested modifications will be necessary.
Ontogeny of B cell precursors responding to alpha 1- greater than 3 dextran in BALB/c mice.
Authors: Stohrer R , Kearney J 
Published: December 2022

Abstract
The ontogeny of BALB/c B cell repertoire with specificity for alpha 1- greater than 3 dextran (DEX) was examined by using monoclonal anti-idiotype antibodies (MAID). Anti-DEX B cell precursors were absent from donor mice that were less than 5 days old. Precursors were first detected in mice from 5 to 11 days of age, but at a very low frequency of less than 1 in 10(8). In older mice, the frequency of anti-DEX precursors increased to approximately adult levels. Seventy-five percent of splenic foci from 5 to 11-day-old donors expressed IgA, and 70% expressed both IgM and IgA. The frequency of DEX-positive foci containing secreted IgA and IgM-IgA decreased as the age of the donors increased. The frequency of IgM-secreting foci remained constant at about 90% of DEX-positive foci regardless of donor age. The frequency of the MAID-defined cross-reactive idiotype CD3-2 and the EB3-16 idiotype changed very little in frequency with age, whereas the EB3-7 and LA4-8 idiotypes increased in frequency as donor age increased. Conversely, the SJL18-1 idiotope that was predominant at days 5 to 11 decreased in frequency relative to total DEX-positive foci as the age of the donors increased. The ratio of M104E-like and J558-like molecules from neonatal B cell precursors is reversed from that expressed by adult B cell precursors, and may reflect the preferential expansion of precursors bearing certain idiotypes by environmental antigens.
Evidence for two distinct activation states available to B lymphocytes.
Authors: Wetzel G D , Swain S L , Dutton R W , Kettman J R 
Published: December 2022

Abstract
The sites and modes of action of several B cell mitogens and interleukins were examined. Cell cycle analyses of B cell responses to several polyclonal activators including LPS, DXS, LPS plus DXS, and anti-immunoglobulin were performed. Two different states of B cell activation distinguished by RNA content, DNA content, and cell size were observed. LPS promoted transitions throughout the cell cycle, whereas DXS primarily caused exit from G0. Synergy between LPS and DXS was observed in elicitation of exit from G0. Activation by anti-immunoglobulin was found to be influenced by the antibody dose and the cell density of culture. Interleukins could influence anti-IgM-induced responses by increasing G0 exit, and by increasing commitment to DNA synthesis. A model of B cell activation in which cells are stimulated to a stage with intermediate RNA levels (G1A) by polyclonal activators is suggested. Some interleukins appear to be involved in this process. At G1A, cells are receptive to signals delivered by interleukins or some polyclonal activators that drive them to late G1 and DNA synthesis. After cell division, cells re-enter G1A in which interleukins or mitogens are necessary for a continued response.
Recognition and response to alloantigens in vivo. II. Priming with accessory cell-depleted donor allogeneic splenocytes: induction of specific unresponsiveness to foreign major histocompatibility complex determinants.
Authors: Ryan J J , Gress R E , Hathcock K S , Hodes R J 
Published: December 2022

Abstract
Although the role of non-T, non-B Ia+ accessory cells as the cells that stimulate alloreactive T cells in vitro has been carefully examined, the capacity of such accessory cells to trigger host T cells in vivo has been considerably less well studied. Therefore, to address the latter issue, this investigation compared the ability of accessory cell-containing and accessory cell-depleted donor cells to mediate in vivo negative and positive selection of mixed lymphocyte reaction (MLR)-responsive peripheral blood lymphocytes (PBL). It was observed that both unseparated and accessory cell-depleted (Sephadex G-10-passed) allogeneic splenocytes, which expressed similar levels of Ia antigens as detected by flow cytometry, were equally efficient in inducing temporary specific unresponsiveness to alloantigens in host PBL 24 hr after donor cell injection. In contrast, 4 days after priming with unseparated major histocompatibility complex (MHC)-incompatible splenocytes, specific MLR hyperresponsiveness was detected in the PBL of these recipient mice, whereas specific hyporesponsiveness was consistently noted in animals injected with accessory-cell depleted splenocytes. PBL obtained from this latter group of mice continued to be specifically reduced in MLR proliferative capacity throughout the culture period and for at least 13 days after administration of accessory cell-depleted allogeneic splenocytes. Mixture of these MLR hyporesponsive and hyperresponsive PBL did not identify suppressor cells as responsible for the specifically lowered proliferative potential. These findings are discussed in the context of discrete signals required for T cell recognition and T cell activation.
Functional clonal deletion of class I-specific cytotoxic T lymphocytes by veto cells that express antigen.
Authors: Rammensee H G , Fink P J , Bevan M J 
Published: December 2022

Abstract
Intravenous injection of class I incompatible spleen cells into mice results in a drastic reduction of the recipient's cytotoxic T lymphocyte (CTL) response against the injected, but not against third party, class I antigens when measured in bulk cultures initiated 5 to 6 days after the injection. This specific suppressive effect is partly due to T cells but can also be seen when high numbers of anti-Thy-1 and complement-treated spleen cells of nude mice are injected. Such cells suppressing CTL responses against self histocompatibility antigens are called "veto cells." The precursor frequency of CTL specific for the injected class I antigen is found to be reduced greater than 200-fold at days 5 to 6 after the injection, whereas the frequencies of CTL specific for third party class I antigens are not significantly changed. These results indicate that there is a functional clonal deletion of the CTL recognizing class I incompatible veto cells in vivo. The role of such a veto phenomenon in the induction and maintenance of self tolerance and allograft tolerance is discussed.
Tumor-activated NK cells trigger monocyte oxidative metabolism.
Authors: Pohajdak B , Gomez J L , Wilkins J A , Greenberg A H 
Published: December 2022

Abstract
We have examined the hypothesis that tumor cells can stimulate a respiratory burst by human natural killer (NK) cells in vitro as measured by luminol-dependent chemiluminescence (CL). Percoll-purified NK cells, containing 40% HNK-1+ cells and less than 1 to 4% esterase-positive contaminating monocytes, can generate a strong CL response after stimulation with the NK-susceptible K562 tumor but not with the NK-resistant P815 tumor cells. Although the response was NK dependent, as shown by depletion with NK-directed monoclonal antibodies (HNK-1, OKT-11, and OKM-1), the cell generating the CL response was not the NK cell. On the basis of several independent experimental approaches the CL response always required the presence of monocytes in the NK preparation. a) Treatment with a monocyte-specific monoclonal antibody (MO2) and complement completely abolished CL. b) The cells producing the CL response were strongly adherent to nylon wool columns (NWC), and large granular lymphocyte preparations containing less than 0.1% esterase-positive cells were inactive. c) NK cells cultured in IL 2-containing medium and tested over several days did not generate CL. d) Optimal numbers of monocytes (less than 1 to 2%) added to a non-CL NWC-purified NK population restored CL, whereas larger or smaller amounts were ineffective. Neither these procedures nor the addition of superoxide dismutase (which completely blocked CL) had any effect on NK lytic activity. We subsequently demonstrated that a factor present in supernatants obtained from NK/K562 incubations, but not from NK or tumor cells alone, could stimulate monocyte CL. We therefore propose that the CL response measured in NK-enriched Percoll fractions originated from contaminating monocytes that were triggered by factor(s) released from tumor-activated NK cells, and that superoxide anion was not required for NK lysis.
The role of the transferrin receptor in human B lymphocyte activation.
Authors: Neckers L M , Yenokida G , James S P 
Published: December 2022

Abstract
Transferrin receptors are expressed on proliferating cells and are required for their growth. Transferrin receptors can be detected after, but not before, mitogenic stimulation of normal peripheral blood T and B cells. T cells demonstrate a functional requirement for transferrin receptors in the activation process. These receptors, in turn, are induced to appear by T cell growth factor (interleukin 2). In the experiments reported here, we examined the regulation of transferrin receptor expression on activated human B cells and whether these receptors are necessary for activation to occur. Activation was assessed by studying both proliferation and immunoglobulin secretion. We determined that transferrin receptor expression on B cells is regulated by a factor contained in supernatants of mitogen-stimulated T cells (probably B cell growth factor). This expression is required for proliferation to occur, because antibody to transferrin receptor (42/6) blocks B cell proliferation. Induction of immunoglobulin secretion, however, although dependent on phytohemagglutinin-treated T cell supernatant, is not dependent on transferrin receptor expression and can occur in mitogen-stimulated cells whose proliferation has been blocked by anti-transferrin receptor antibody. These findings support a model for B cell activation in which mitogen (or antigen) delivers two concurrent but distinct signals to B cells: one, dependent on B cell growth factor and transferrin receptor expression, for proliferation; and a second, dependent on T cell-derived factors and not requiring transferrin receptors, which leads to immunoglobulin secretion.
Regulation of human B cell proliferation by prostaglandin E2.
Authors: Thompson P A , Jelinek D F , Lipsky P E 
Published: December 2022

Abstract
The role of prostaglandin E2 (PGE2) in the regulation of human B cell proliferation in vitro was examined. Initial studies demonstrated that monocyte (M phi)-mediated suppression of B cell proliferation in Staphylococcus aureus (SA)-stimulated cultures was diminished by indomethacin, and thus it was suggested that cyclooxygenase pathway products of arachidonic acid played a role in the regulation of B cell activation. The possibility that PGE2, one of the major products of this pathway generated by M phi, affected human B cell responses was therefore investigated. PGE2 was found to suppress B cell DNA synthesis and proliferation stimulated by SA in the presence or absence of B cell growth factor (BCGF)-containing T cell supernatants. Suppression was concentration-dependent; significant inhibition was observed in indomethacin-blocked cultures with 10(-10) to 10(-9) M PGE2. In contrast to the effect of PGE2 on SA-induced B cell proliferation, it had minimal effect on pokeweed mitogen (PWM)-stimulated B cell or T cell DNA synthesis. The effect of PGE2 on the generation of BCGF activity from mitogen-stimulated T cells was also examined. PGE2 (10(-7) M) did not inhibit the production of BCGF activity from PWM-stimulated T cells, or from T cells stimulated with the combination of phytohemagglutinin and phorbol myristate acetate. Thus, PGE2 inhibits B cell proliferation in response to SA but not PWM, and has little effect on the production of BCGF by T cells. These results indicate that PGE2 at physiologically relevant concentrations exerts selective regulatory effects on human B cell responses.
Mitogen-induced human IgG subclass expression.
Authors: Scott M G , Nahm M H 
Published: December 2022

Abstract
To investigate human isotype expression among lymphocyte populations, we have studied IgG subclass production by splenocytes, tonsil cells, and peripheral blood lymphocytes (PBL) after stimulation with a panel of nine mitogens. Response magnitudes varied with tissues: all mitogens produced the strongest responses with splenocytes and the smallest with PBL. In addition, the IgG subclass maximally stimulated by a particular mitogen also depended on the tissue studied. For example, LPS mainly stimulated IgG2 in PBL and IgG1 in spleen. Interestingly, the response patterns seen in splenocytes suggest a large and coordinate expression of IgG1 and IgG3 subclasses. Implications of these findings are discussed with respect to immunoglobulin gene organization and human disease states.
Recognition of two Dermatophagoides pteronyssinus-specific epitopes on antigen P1 by using monoclonal antibodies: binding to each epitope can be inhibited by serum from dust mite-allergic patients.
Authors: Chapman M D , Sutherland W M , Platts-Mills T A 
Published: December 2022

Abstract
Monoclonal antibodies were raised against Antigen P1, the major allergen of the house dust mite (Dermatophagoides pteronyssinus). The majority were Antigen P1 specific, isotype IgG1, and did not react with a comparable D. farinae allergen. These antibodies bound 38 to 50% of 125I Antigen P1 in antigen-binding assays (titer greater than or equal to 1/1,000,000), and the quantities of IgG antibody in ascites were 2 to 4 logs greater than those in polyclonal mouse antiserum or in serum from a mite-allergic patient. Two IgM antibodies showed weak binding to Antigen P1 but reacted strongly with D. pteronyssinus in enzyme immunoassay (titer greater than or equal to 1/100,000). Assessments of the specificity of the IgG antibodies by using two inhibition radioimmunoassays suggested that they were directed against two different epitopes. Antibodies 10B9 F6 and 5H8 C12 were purified by preparative isoelectric focusing (isoelectric points of pI 6.25 and 7.4, respectively) and radiolabeled with 125I. Cross-inhibition experiments, using ascites dilutions to inhibit binding of each radiolabeled antibody to Antigen P1, confirmed that these antibodies recognized two distinct epitopes. Analysis of antibodies from 39 clones/hybrids showed that the majority were directed against the same epitopes as either 10B9 F6 or 5H8 C12 (3 out of 39 [8%] and 29 out of 39 [74%], respectively). None of the monoclonal antibodies significantly inhibited (greater than 10%) human IgE binding to Antigen P1 in the radioallergosorbent test. However, 12 of 14 sera from mite allergic patients inhibited binding by the monoclonal antibodies. One serum from a mite-allergic patient inhibited binding of both 10B9 F6 and 5H8 C12 by greater than 85% and showed parallel inhibition curves. The results suggest that these monoclonal antibodies could be used to assay Antigen P1 in both D. pteronyssinus and house dust extracts. It should also be possible to use monoclonal antibodies in inhibition assays to define the antigenic/allergenic determinants recognized by human IgG and IgE antibodies on this mite allergen.