bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Bordetella pertussis leukocytosis (lymphocytosis)-promoting factor (LPF) on the physical lymphoepithelial-cell association studied with the use of an in vitro model of mouse thymus.
Authors: Sugimoto M , Nakanishi Y , Otokawa M , Uchida N , Yasuda T , Sato H , Sato Y 
Published: December 2022

Abstract
The effect of highly purified leukocytosis (lymphocytosis)-promoting factor (LPF) of Bordetella pertussis on physical lymphocyte and reticuloepithelial (RE) cell association was studied in an in vitro thymus model. First, a simplified in vitro system to assess the lympho-RE-cell association was developed. A completely confluent layer of thymic RE cells was formed by cultivating trypsinized thymus cell suspensions from 2- to 7-day-old mice. When thymic lymphoid cells were seeded on this cell layer and cultivated overnight, a significant proportion of them were found underneath the RE cell layer. This physical lympho-RE-cell association was quantitated by counting the lymphoid cells underneath the RE cell layers. Second, the effect of LPF on this physical lympho-RE-cell association phenomenon was investigated. Addition of LPF to the culture markedly inhibited the formation of the lympho-RE-cell complex; that is, it inhibited the infiltration of lymphoid cells under the RE cell layer. LPF rendered a nearly maximal level of inhibitory effect at a dose of 0.1 ng/ml. Furthermore, LPF enhanced the liberation of lymphoid cells from preformed lympho-RE-cell complexes. On the other hand, LPF had no direct cytotoxic effect on lymphoid cells at doses below 1 microgram/ml. In order to investigate whether LPF produced the effect by acting on lymphoid cells, RE cells, or both, the following experiments were performed. When lymphoid cells were pretreated with LPF and added to normal RE cell layers, the lympho-RE-cell association was maximally inhibited above the dose of 1 ng/ml. Treatment of these LPF-treated lymphoid cells with anti-LPF antibodies failed to abrogate the effect of LPF. When RE cell layers were similarly pretreated with LPF and were cultivated with normal lymphoid cells, however, much higher doses of LPF, above 100 ng/ml, were required for maximal inhibition. Furthermore, treatment of these LPF-treated RE cells with anti-LPF antibodies abrogated the effect of LPF. Therefore, the apparent effect of LPF on RE cells was considered to be due to the carry-over by RE cells of LPF, which should directly act on lymphoid cells at extremely low doses. On the basis of these results, it was concluded that LPF acted directly on lymphoid cells without mediation of RE cells. These in vitro results appear to parallel the effects of LPF in vivo, where it induces a depletion of cells in the thymus. The model may be useful to study this phenomenon and the concomitant accumulation of blood lymphocytes.
Conversion of lipopolysaccharides to molecular aggregates with reduced subunit heterogeneity: demonstration of LPS-responsiveness in "endotoxin-unresponsive" C3H/HeJ splenocytes.
Authors: Vukajlovich S W , Morrison D C 
Published: December 2022

Abstract
Lipopolysaccharides (LPS) of homogeneous monomeric composition were prepared by gel filtration chromatography of detergent-dissociated LPS from the smooth strain of E. coli 055:B5. Splenocyte mitogenic activity of reassociated column fractions and fraction pools is markedly dependent upon the ratio of O-antigen polysaccharide to lipid A. The activity of the homogeneous LPS in eliciting spleen cell responses varied by approximately three orders of magnitude. One of the fraction pools rich in lipid A (which contains only a trace of O-antigen polysaccharide) induces a spleen cell proliferative response in C3H/HeJ "LPS-nonresponder" spleen cells. This mitogenic activity is not present in either unfractionated LPS or O-antigen-rich fractions. These latter findings indicate LPS macromolecular aggregates of the appropriate physicochemical structure have the capacity to elicit C3H/HeJ spleen cell proliferative responses.
C3 receptors on human lymphocyte subsets and recruitment of ADCC effector cells by C3 fragments.
Authors: Wåhlin B , Perlmann H , Perlmann P , Schreiber R D , Müller-Eberhard H J 
Published: December 2022

Abstract
The presence of C3 receptors on human peripheral blood lymphocytes (PBL) and on the ADCC-exhibiting subset (K cells) thereof was analyzed by rosetting with bovine erythrocytes (Eb) or chicken erythrocytes (Ec) carrying human C3b, C3bi, or C3d. The indicator cells were coated with 20,000 to 100,000 C3 fragments, obtained by C3 activation with purified proteins of the alternative pathway and trypsin treatment. ADCC was studied at the cellular level by means of a plaque assay, with complement-free or complement-carrying indicator cells as targets. Of the total lymphocytes, 12 to 14% bound EC3b; 6 to 8%, EC3bi; and approximately 2%, EC3d. Surface marker analysis indicated that approximately 75% of the C3b-binding lymphocytes in PBL were either B or null cells and approximately 60% of the C3bi-binding cells were T cells, as characterized by the monoclonal antibodies OKT3 and OKT4 or by presence of receptors for Helix pomatia hemagglutinin. Of the K cells, which constituted from 5 to 10% of the total lymphocytes, approximately 20% bound C3b; 30 to 35%, C3bi; and 7 to 8%, C3d. Here the majority of the C3b binders were null cells, and the majority of the C3bi and C3d binders were T cells. Only one-third of the C3b-binding K cells and one-fifth of the C3bi-binding K cells bound both fragments. The nature of these double binding cells is unknown. In contrast, all C3d-binding K cells bound C3bi as well. C3 fragment-carrying target cells did not induce K cell-mediated lysis in the absence of anti-target antibodies but strongly enhanced ADCC in the presence of sublytic concentrations of such antibodies. The rank order for C3 fragment-induced enhancement was C3bi greater than C3d greater than C3b. It reflected the relative proportions of effector cells binding the different fragments. Enhancement was the expression of effector cell recruitment rather than of increased cytolytic activity of individual K cells. This recruitment was selective in that C3b-carrying target cells primarily recruited effector cells of null type, binding C3b, while C3bi- or C3d-carrying targets primarily recruited C3bi and/or C3d-binding K cells of T gamma type. Thus, these experiments show directly at the effector cell level that cell-bound C3 fragments constitute important recognition structures, which strongly amplify ADCC both by recruiting the proper effector cells into the cytolytic reaction and by very significantly decreasing the antibody concentration needed for its induction.
Altered oxidative metabolism in selenium-deficient rat granulocytes.
Authors: Baker S S , Cohen H J 
Published: December 2022

Abstract
Rats fed a selenium-deficient diet for 12 to 15 wk became selenium-depleted, measured by the selenium content of liver and granulocytes. The activity of granulocyte glutathione peroxidase, a selenoenzyme, in deficient rats was 11% of the activity in replete rat granulocytes. When stimulated with an H2O2 generating system, the HMPS activity of the deficient granulocytes was 50% of replete; however, when stimulated with methylene blue, the HMPS activity in deficient and replete granulocytes was the same. When granulocytes were incubated with PMA or OPZ, deficient granulocytes initially had the same O-2-generating activity as replete granulocytes; however, with increasing duration of stimulation, granulocytes from deficient rats generated less O-2 than replete rats. After 20 min in an H2O2-generating system, deficient granulocytes stimulated with PMA or OPZ generated less O-2 than replete granulocytes. These results indicate that deficient granulocytes did not metabolize H2O2 as well as replete granulocytes and that H2O2 caused damage to the O2-generating system. Measurement of O-2 generation in membrane-enriched particles showed the above effects were due to inactivation of the NADPH-dependent O2-generating system. Deficient granulocytes stimulated with OPZ for 20 min had 70% less membrane O-2-generating activity than controls. In addition, when membrane-enriched particles were made from cells that had been stressed with an H2O2-generating system, NADPH-dependent O-2-generating activity in deficient granulocytes was 50% of replete. In selenium-deficient granulocytes with low GSH-Px activity, prolonged incubation with stimulants and prior incubations with an H2O2-generating system caused loss of activity of the membrane-bound, NADPH-dependent, O-2-generating system.
Regulation of cell-mediated immunity in cryptococcosis. II. Characterization of first-order T suppressor cells (Ts1) and induction of second-order suppressor cells.
Authors: Murphy J W , Mosley R L , Moorhead J W 
Published: December 2022

Abstract
Cryptococcosis patients frequently have high levels of cryptococcal antigen in their body fluids, and the levels of circulating antigen can generally be used to predict the patient's recovery, with high or rising antigen titers indicating a poor prognosis and low or decreasing levels a good prognosis. In a previous study, we reported on a murine model for studying the effects of cryptococcal antigen on host defense mechanisms. In that work, we demonstrated that an i.v. injection of cryptococcal antigen (CneF) into CBA/J mice, to simulate the antigenemia known to occur in human cryptococcosis, induced a population of T suppressor cells (Ts1) in the lymph nodes (LN). Upon adoptive transfer, the Ts1 cells specifically suppressed the afferent limb of the delayed-type hypersensitivity (DTH) response to cryptococcal antigen. In the present study, we show that the precursors of the Ts1 cells are sensitive to low-dose cyclophosphamide treatment and that the phenotype of the Ts1 cells is Lyt-1+, Ia+ (I-J+). LN cells from CneF-injected mice or a soluble factor derived therefrom can induce in the spleens of recipient mice a second-order suppressor cell population that suppresses the efferent limb of the DTH response. The cells that induce the second-order or efferent suppressor cells have the same phenotype as the cells that appear to suppress the afferent limb of the DTH response. The findings in this study indicate that a complex regulatory mechanism is responsible for the observed suppression of the DTH response in this infectious disease model. Furthermore, the suppressive circuit thus far defined for cryptococcal antigen is similar to the antigen-specific suppressor cell pathway outlined for certain chemically defined haptenic systems.
Monoclonal antibody against a differentiation antigen on human leukemia cells: cross-reactivity with rat leukemia and suppression of rat leukemia in vivo.
Authors: Johnson R J , Shin H S 
Published: December 2022

Abstract
We produced a McAb against a normal differentiation antigen on human ANLL that cross-reacts with a rat ANLL. The McAb reacted with all ANLL cells tested as well as normal undifferentiated myelomonocytic cells. This McAb, of the IgM isotype, in the presence of C mediated lysis of human and rat leukemic cells in vitro. In addition, it mediated complete tumor suppression in rats engrafted with 10(2) to 10(3) rat leukemic cells in vivo. No significant side effects were observed in McAb-treated rats. McAb of this type may be useful in the treatment of human ANLL after conventional therapy, which often eliminates most leukemic cells, leaving a small number of residual cells. The ultimate utility of this McAb for human therapy or McAb directed against the same or other differentiation antigens remains to be determined.
Studies on the mechanism of natural killer cell-mediated cytotoxicity. IV. Interferon-induced inhibition of NK target cell susceptibility to lysis is due to a defect in their ability to stimulate release of natural killer cytotoxic factors (NKCF).
Authors: Wright S C , Bonavida B 
Published: December 2022

Abstract
The effects of interferon (IFN) at the level of the target cell in the natural killer cytotoxic factors (NKCF) system have been examined to determine whether they correlate with the effects of IFN in natural killer (NK) cell-mediated cytotoxicity (CMC). NKCF are released into the supernatant of co-cultures of murine spleen cells and YAC-1 stimulator cells, and their lytic activity is measured against YAC-1 target cells. It was found that IFN-pretreated YAC-1 target cells were still sensitive to lysis by NKCF, although their ability to stimulate release of NKCF from murine spleen cells was impaired. This defect was not due to a lack of NK target structures, because IFN-pretreated YAC-1 cells form a normal number of conjugates with spleen cells. The defect also could not be attributed to an IFN-induced inhibition of protein synthesis, because emetine-pretreated YAC-1 stimulator cells can still induce the release of high levels of NKCF. Cellfree supernatants containing NKCF also contain low levels of endogenous IFN (10 to 50 U/ml). Although this concentration of IFN itself is not toxic to YAC-1 cells, it may still interact with NKCF and/or the target cell to enhance cytotoxicity mediated by NKCF. Evidence in support of this possibility is derived from experiments that demonstrated that addition of exogenous IFN to NKCF resulted in a synergistic enhancement of cytotoxicity. Taken together, these findings can account for the IFN-induced inhibition of target cell susceptibility to lysis in the NK CMC system. In addition, the evidence supports our model for the role of NKCF in the mechanism of NK CMC. According to this model, the effector cell must first bind to the target cell; then the target cell delivers a signal to the effector cell to activate the NKCF release mechanism. The effector cell releases NKCF that then bind to the target cell and mediate cell lysis. The mechanism by which IFN-pretreated target cells become relatively NK-resistant appears to be a defect in their ability to stimulate the effector cell to release NKCF after the initial effector-target cell binding.
Immune capacity of the chicken bursectomized at 60 hours of incubation: mitogen-induced cell proliferation and immunoglobulin secretion.
Authors: Eerola E , Jalkanen S , Granfors K , Toivanen A 
Published: December 2022

Abstract
Chickens were bursectomized surgically at 60 hr of incubation. Bone marrow cells from the bursectomized (Bx) and control (Co) chickens responded equally well by proliferation to B cell mitogens (dextran sulfate, anti-mu, anti-gamma) when studied at the age of 10 weeks. In contrast, spleen cells of Bx chickens responded significantly less to anti-mu and anti-gamma than did spleen cells of the Co chickens. When observed at the age of 10 days, a significantly depressed secretion of IgM, IgG, and IgA by the Bx cells was observed in vitro. This difference between the Bx and Co chickens had disappeared when studied at the age of 10 weeks.
Blockade of Fc receptor-mediated binding to U-937 cells by murine monoclonal antibodies directed against a variety of surface antigens.
Authors: Kurlander R J 
Published: December 2022

Abstract
The effect of murine IgG hybridoma antibodies directed against leukocyte antigens on the Fc receptor function of human cells was studied. For this purpose, the specific binding of 125I-labeled monomeric human IgG1 to a macrophage-like cell-line (U-937) was quantitated before and after incubation in the presence of murine monoclonal hybridoma antibodies. Four monoclonal hybridoma antibodies (A1G3, 23D6, 4F2, and 3A 10), each of which binds to different antigens on the surface of U-937 cells, rapidly and potently inhibited the specific binding of labeled IgG1 to these cells. Inasmuch as inhibition was mediated only by IgG antibodies with an intact Fc fragment and antibody activity against surface antigens found on U-937, inhibition appears to have resulted from the formation of a three-component complex composed of antibody bound by its Fab portion to antigen and by its Fc fragment to a Fc receptor. Equilibrium binding studies performed on treated cells confirmed that reduced Fc receptor-mediated binding was due to a reduction in the number of available receptors. Binding studies employing double isotope labeling methods demonstrated that about 0.5 to 1.0 Fc receptor was blocked for each molecule of intact antibody bound to a U-937 cell. Using several techniques, it was shown that most of the monoclonal antibody bound to cells and the Fc receptors blocked by antibody remained on the cell surface despite incubation at 37 degrees C for 3 hr. Thus, the loss of receptor function observed in these experiments was almost exclusively due to reversible receptor blockade rather than receptor internalization or degradation. The antibodies identified in these studies also markedly inhibited Fc receptors on one other human cell line (HL-60) as well as those on normal human peripheral blood monocytes.
Identification and functional characterization of two distinct epitopes on the human T cell surface protein Tp50.
Authors: Martin P J , Longton G , Ledbetter J A , Newman W , Braun M P , Beatty P G , Hansen J A 
Published: December 2022

Abstract
The structural and functional domains of Tp50, the human T lymphocyte surface protein associated with the E rosette receptor, were probed with the use of two murine monoclonal antibodies. Lysostripping, immune precipitation, and competitive binding experiments demonstrated that antibodies 9.6 and 35.1 bind to Tp50 epitopes in close proximity. In functional studies, both antibodies caused a similar degree of antigenic modulation, inhibited T cell proliferative responses, and inhibited cytotoxic T lymphocyte function without affecting cells that mediate antibody-dependent cell-mediated cytotoxicity. The antibodies were strikingly different, however, in that antibody 9.6 inhibited E rosette formation and natural killer cell-mediated lysis, whereas antibody 35.1 did not. These results could not be ascribed to differences in antibody class or binding characteristics, because Scatchard analysis demonstrated that these two IgG2a antibodies have comparable avidity and that T cells bind each antibody in equivalent amounts. The differential binding of antibodies 9.6 and 35.1 to T cells from nonhuman primates further supports the interpretation that the differences between the antibodies in their effects on E rosette formation and natural killer function stem from the fact that they bind to distinct epitopes of Tp50. The implications of these findings for understanding the functions of Tp50 molecules are discussed.
Con A-induced TCGF-reactivity is selectively acquired by Lyt-2-positive T cell precursors.
Authors: Gullberg M , Larsson E L 
Published: December 2022

Abstract
We investigated whether concanavalin A-stimulated, TCGF-reactive, and TCGF-producing T cells could be separated with regard to their Lyt phenotypes. Normal spleen cells, pretreated with monoclonal anti-Lyt-1 or anti-Lyt-2 antibodies and complement were assayed for their capacity to respond to TCGF, as well as for their ability to produce TCGF after Con A stimulation. The results demonstrate that reactivity to TCGF is predominantly induced in Lyt-2+ lymphocytes, because it is reduced by more than 95% in Lyt-1+23- T cell populations as compared with cultures containing Lyt-1-23+ cells. Limiting dilution analysis revealed that up to 20% of the cells in Lyt-2-containing populations were induced by Con A to TCGF-reactivity, whereas 20-fold fewer clones were induced in the Lyt-2-depleted cell populations. On the other hand, the study of TCGF production in Lyt-1-23+ populations revealed that the former population was considerably enriched in TCGF-producing T cells, whereas the latter was substantially depleted. We conclude that TCGF-producing and TCGF-reactive T cells are largely distinct lymphocyte populations that can be separated on the basis of their Lyt phenotypes.
B4, a human B lymphocyte-associated antigen expressed on normal, mitogen-activated, and malignant B lymphocytes.
Authors: Nadler L M , Anderson K C , Marti G , Bates M , Park E , Daley J F , Schlossman S F 
Published: December 2022

Abstract
The characterization of a new B cell-specific antigen (B4) is described in this report. With the use of a monoclonal antibody to B4, it was shown that B4 is present on B cells isolated from peripheral blood and lymphoid organs, on cell lines derived from normal and malignant B cells, and on tumor cells isolated from patients with B cell-derived neoplasms. B4, in contrast, was not detected on normal, activated, or malignant cells of T or myeloid origin. The B4 antigen is distinct from known B cell antigens, including sIg, Ia, B1, B2, Fc, and C3. Examination of mitogen-stimulated B lymphocytes suggests that the B4 antigen initially increases with B cell activation and then is lost at the terminal stage of B cell differentiation. Moreover, the observation that B4 is expressed on almost all early B cell tumors suggests that it may precede B1, CALLA, cytoplasmic mu, and B2 in early B cell ontogeny.
In vivo and in vitro production of anti-histone antibodies in NZB/NZW mice.
Authors: Gioud M , Kotzin B L , Rubin R L , Joslin F G , Tan E M 
Published: December 2022

Abstract
Anti-histone antibodies have been demonstrated in the sera of patients with both idiopathic and drug-induced lupus. We measured anti-histone antibodies in female NZB/NZW (F1) mice, which are considered to be a model of human SLE. Using a sensitive and quantitative enzyme-linked immunosorbent assay (ELISA), we detected minimal serum antibody activity in NZB/NZW mice younger than 4 mo of age and in nonautoimmune mice at all ages tested. Serum anti-histone antibodies progressively increased in NZB/NZW mice from 4 to 8 mo of age and showed an age-related maturation from IgM to IgG. The predominant antibody activity in the older mice was to the individual histones H2B and H3, and the pattern of reactivity to the histone proteins was similar to that seen in human SLE. We also studied the spontaneous in vitro production of anti-histone antibodies using spleen cells from NZB/NZW mice of different ages. Culture supernatants were analyzed for antibody activity by an ELISA with total histones as the antigen. Spleen cells from older NZB/NZW mice, with elevated serum levels, produced 10-fold higher levels of antibody activity compared to age-matched nonautoimmune mice. Antibody production was maximal at 4 days of culture and was inhibited by the addition of puromycin to the culture. Surprisingly, spleen cells from 1 to 3-mo-old NZB/NZW mice, with normal serum levels, also demonstrated significantly elevated production. The antibodies produced by these young mice were mostly IgM, whereas spleen cells from older mice produced mostly IgG anti-histone antibodies. The present results provide the basis for using the anti-histone antibody system to study further the immune abnormalities that allow for autoantibody production.