bluuebunny/crossref_metadata_2025_split huggingface dataset:
Receptor Cross-Linking and Histamine Release
Authors: DeLisi Charles , Siraganian Reuben P. 
Published: December 2022

Abstract
We develop and apply a mathematical method for relating the number of antigen-induced IgE clusters on the basophil plasma membrane to the amount of histamine released. The method is valid at low doses of antigen where, it is shown, the number of bound antigens and the number of IgE clusters are linearly proportional to the total concentration of antigen. Cross-linking of receptors on some portion of the surface is considered to be a necessary condition for transmission of a signal that leads to degranulation. No assumption is made about whether the degranulation thus stimulated is local or global. Analysis of the low-dose portion of the dose-response curve, however, indicates the following: 1) Degranulation is local, and the maximum number of local centers per cell (“compartments”) is small (≤ 10). 2) The number of IgE clusters required to initiate such local release is small but variable and depends upon the cell source and antigen valence. The results varied between three and eight for Con A, AgE, and anti-IgE. 3) These numbers represent thresholds for release; i.e., to a good approximation some minimum number of antigens in excess of one must be multiply bound before any histamine can be released. This suggests a high degree of cooperativity in the biochemical sequelae to clustering. 4) Only a small fraction of clusters are transmitting a release signal. This suggests, and is consistent with the idea, that clusters are interacting with some other membrane molecule and that only those that are bound to the other molecule are biologically active. 5) With respect to transmitting a signal for histamine release the number of independent clusters appears to be a more fundamental quantity than the total number of cross-linked receptors; i.e., there is little difference in activity as the size of a cluster increases due to increase in ligand valence.
Receptor Cross-Linking and Histamine Release
Authors: Delisi Charles , Siraganian Reuben P. 
Published: December 2022

Abstract
We report the results and analysis of dose-response and desensitization studies of rabbit basophils by a variety of antigens. Unlike the response of human basophils, the histamine release curves rarely rise and fall in a symmetric fashion, but more often either rise to a plateau, peak, and then fall to a non-zero plateau, or exhibit bimodality. In those cases in which the curves peak, preincubation with antigen in the absence of Ca++ has a smaller effect at the high and low concentration portions of the curve than it does toward the center, where the inhibitory effect is maximum.
We show that the results can be explained by a simple model in which: 1) The signals for release and desensitization both increase as the concentration of receptor cross-links increases and 2) the signals reach a plateau (i.e., they have a maximum value) when the number of receptor cross-links becomes sufficiently large. By changing the parameters of the model, the balance between desensitization and release changes, and all the observed patterns can be reproduced. In particular, if both signals saturate (reach their maximum value) at a ligand concentration below that of maximum cross-linking, the histamine release curve will plateau. If the release signal saturates but the inhibitory signal continues to increase as ligand concentration increases toward its optimum value, the histamine release curve will be bimodal.
Many of the parameters can be identified with those that affect receptor clustering. These include the affinity of IgE for the antigen, the number of IgE molecules per basophil, IgE hinge flexibility, membrane fluidity, and antigen concentration and valence. This identification permits a variety of additional predictions. One such prediction is that the difference between a dose-response curve that plateaus and one that is biphasic and unimodal reflects easier desensitization of cells responsible for the latter curve and/or that have a smaller number of cross-links. Both predictions are readily testable experimentally.
Genetic and Biochemical Evidence for the Involvement of a Bacterial Component in the Mitogenic Properties of Polyribonucleotides on Murine B Lymphocytes
Authors: Kelly Kathleen , Watson James 
Published: December 2022

Abstract
The mitogenic response of C3H/HeJ mice to the B cell mitogens, poly C and poly I, is approximately one-half the response measured in various LPS-responder strains. C3H/HeJ mice respond normally to poly I:C, the heteroduplex polymer. The low responder phenotype of C3H/HeJ mice to poly C and poly I is shown by an analysis of (C3H/HeJ × C57BL/6J-By-Ps)F1 × C3H/HeJ backcross progeny to result from a gene locus that is closely linked or identical to the defective LPS response locus expressed by the C3H/HeJ strain. The entire mitogenic activity in poly C preparations and most of the mitogenic activity in poly I preparations is insensitive to ribonuclease degradation. Hot aqueous phenol extraction of the polynucleotides separates the majority of the mitogenic activity that is soluble in the combined interface and phenol phase fraction from the aqueous soluble polynucleotides. The ribonuclease-insensitive, phenolsoluble contaminant elicits a reduced response in C3H/HeJ mice as compared to an LPS responder strain. We conclude that 1) poly C has no inherent mitogenic activity; 2) poly I preparations contain both ribonuclease-sensitive and insensitive mitogenic activities; 3) the ribonuclease-resistant mitogenic activity in polynucleotide preparations has physical properties unlike those of LPS or lipid A; and 4) the product of the LPS response gene has an effect upon the mitogenic stimulation of spleen cells by the contaminant.
Patterns of Immune Reactivity in Autoimmune Murine Strains
Authors: Theofilopoulos Argyrios N. , Shawler Daniel L. , Katz David H. , Dixon Frank J. 
Published: December 2022

Abstract
We compared spleen cells from immunologically normal mice to those from five autoimmune murine strains (NZB, NZB × W, BXSB, MRL/l, MRL/n) in the cell-mediated lympholytic response in vitro to spleen cells from syngeneic, allogeneic but H-2 identical and H-2 incompatible mice. NZB spleen cells sensitized with irradiated allogeneic but H-2d identical spleen cells lysed unmodified H-2 identical cells in a strong, cross-reactive, unidirectional response, and lysed similarly, but to a lesser extent, syngeneic cells. The NZB anti-H-2d activity was mediated by T cells and was directed against both T and B target cells. Although the anti-H-2d activity is known to be directed against minor histocompatibility differences, it appears from our experiments with congenic mice that the activity is to some extent recognized in the context of the H-2 haplotype, since it was optimum when the NZB cells matched the target cells at the K or D end of H-2.
NZB cells sensitized in vitro by H-2 identical cells were only minimally stimulated to proliferate; however, such cells were able to induce in vivo GVH reactions in NZB mice. Similar in vitro anti-H-2d reactivity was observed with NZB × W spleen cells. In contrast, spleen cells from BXSB, MRL/1, and MRL/n mice were not sensitized in vitro with H-2 identical cells. Spleen cells from all autoimmune murine strains incubated with irradiated syngeneic cells were devoid of any cytolytic activity against syngeneic target cells. Cells from all autoimmune strains sampled during youth exhibited a normal effector function against H-2 incompatible spleen cells, and this function declined moderately with age and appearance of disease. In contrast to all other autoimmune strains, cells from MRL/1 mice were inadequate stimulators with H-2 incompatible cells, possibly due to massive T cell lymphoproliferation seen in these mice. Although the observed anti-H-2d activity of cells from New Zealand mice (NZB, NZB × W) may play a role in the development of their disease, the possibility that such a mechanism serves as a common etiologic pathway in the development of the murine SLE-like syndromes seems unlikely since the other autoimmune strains studied were devoid of such activity.
Antibody Blockade of Lysis by T Lymphocyte Effectors Generated against Syngeneic SV40 Transformed Cells
Authors: Gooding Linda R. 
Published: December 2022

Abstract
Antibody blockade of cell-mediated lysis was used to probe the cell surface structures recognized by T lymphocytes generated to syngeneic SV40 virus-transformed mouse cells. Alloantisera to H-2 antigens were highly effective in inhibiting lysis. Anti-H-2 antibody blockade of lysis was haplotype specific even on transformed F1 target cells. Inhibition occurred only when antibody was bound to the target cell. Antibody binding to the effector did not inhibit lysis. Inhibition required that antibody be bound to the H-2 molecule itself; antibody to molecules associated with H-2, such as β2-microglobulin, had no effect.
Attempts to block lysis by using antisera to known virus-coded molecules were uniformly unsuccessful. These results are discussed in light of current controversy concerning the nature of the SV40 virus-specific transplantation antigen.
Evaluation of the Role of C4 in the Cellular Immune Response in Vitro
Authors: Burger Reinhard , Shevach Ethan M. 
Published: December 2022

Abstract
The demonstration that antisera to human C4 inhibit the human mixed lymphocyte reaction and the response to the mitogen, phytohemagglutin, suggested a possible role of C4 in the afferent phase of immune recognition. An attempt was made to reproduce and extend these observations in the guinea pig. Monospecific antisera to C4 were raised in C4-deficient guinea pigs, rabbit, or goat. The antisera were tested for inhibition of the unidirectional mixed leukocyte reactions between strain 13 and strain 2 guinea pigs, for inhibition of proliferation induced by the mitogens, phytohemagglutinin and concanavalin A, and for inhibition of the proliferative response of immune T lymphocytes to soluble protein antigens. In a large number of experiments no reproducible inhibition was found when the various cultures were performed in the presence of antiserum to C4. Furthermore, lymphocytes from C4-deficient guinea pigs responded as well as lymphocytes from strain 13 animals to specific antigen or in mitogen-induced proliferation, indicating a normal capacity of T cells from C4-deficient animals for recognition of antigen or mitogen and for proliferation. Antigen- or mitogen-pulsed macrophages from C4-deficient guinea pigs were able to effectively stimulate T cell proliferation, suggesting a normal capability for antigen or mitogen presentation. These data argue against a possible role for C4 in antigen, mitogen, or alloantigen-induced T lymphocyte activation and indicate that the demonstrated functional association of C4 and MHC-mediated reactions in the human does not generally apply to another species.
Macrophage-T Cell Interactions Involving Listeria Monocytogenes—Role of the H-2 Gene Complex
Authors: Farr Andrew G. , Kiely Jeanne-Marie , Unanue Emil R. 
Published: December 2022

Abstract
This study reports on the in vitro interactions between T cells from Listeria-immunized mice, macrophages from normal mice, and heat-killed Listeria organisms. This interaction was assayed either by determining the amount of a thymocyte mitogen in culture fluids after 24 hr, or by estimating the degree of T cell proliferation after 96 hr. Each assay depended on critical concentrations of macrophages, T cells, and heat-killed Listeria, points that were evaluated in a number of experiments. Both assays required specific Listeria-immune T cells. For an effective interaction, the T cells and the macrophages had to share the I-A region of the H-2 gene complex. Macrophages bearing Ia, which represented a minor population of macrophages, were essential for the proliferative response to macrophage-associated Listeria. Also, Ia-bearing macrophages were an important component in the interactions leading to increased secretion of mitogen. The immunogenic moiety associated with Listeria was short-lived, disappearing 24 hr after uptake of Listeria by macrophages. The interactions were not blocked by anti-Listeria antibodies but were partially sensitive to trypsinization.
Tumor-Basophil Interactions in Vitro—A Scanning and Transmission Electron Microscopic Study
Authors: Dvorak Ann M. , Galli Stephen J. , Galli Anne S. , Hammond M. Elizabeth , Churchill W. Hallowell , Dvorak Harold F. 
Published: December 2022

Abstract
Purified guinea pig basophils, or basophils either specifically degranulated with antigen or nonspecifically degranulated with lectin, were cultured with guinea pig line 1 hepatoma cells for 1 to 24 hr and studied ultrastructurally. As early as 1 hr of culture, degranulated or nongranulated basophils and tumor cells formed close contacts by mutually intertwined elongated cell processes and also in cultures containing degranulated basophils, extruded membrane-free basophil cytoplasmic granules became firmly attached to tumor cells. At later intervals, some tumor cells cultured with basophils exhibited cytostatic and cytopathic changes, including dense mitochondria, centralization of organelles, dilated perinuclear and rough endoplasmic cisternae, cell swelling and cytoplasmic lucency, disrupted cytoplasmic organelle and plasma membranes, nuclear pyknosis and fragmentation. Some tumor cell specialized surface attachments were either disrupted or damaged at points of basophil or basophil granule adhesion. Tumor damage was most extensive in cultures containing degranulated basophils, although only a minority of tumor cells (&lt;10%) was affected. Tumor injury was seen much less frequently in the presence of nondegranulated basophils, and was absent in control cultures of tumor alone. The occasional viable tumor cells that phagocytosed basophil granules were apparently unharmed, suggesting that internalization of basophil granules by tumor cells is not cytotoxic.
Lymphocytes Bearing Fc Receptors for IgE
Authors: Yodoi Junji , Ishizaka Kimishige 
Published: December 2022

Abstract
Human peripheral blood lymphocytes from ragweed-sensitive individuals were fractionated by a rosette technique with neuraminidase-treated sheep erythrocytes (En). A significant number of FcεR-bearing cells were detected in the T cell fraction by rosette formation with ox erythrocytes coated with human IgE (E'-hIgE), or by the binding of fluoresceinated F(ab′)2 fragments of anti-IgE complexed with IgE. The majority of these lymphocytes in the T cell fraction formed mixed rosettes with En and E'-hIgE. T cells bearing FcεR were demonstrated in the mesenteric lymph node cells from rats infected with Nippostrongylus brasiliensis (Nb); about 3% of the total cells in a B-depleted fraction formed rosettes with ox erythrocytes coated with rat IgE (E'-rIgE). Most of the rosette-forming cells (RFC) in the fraction were stained by antibodies specific for rat T cells in immunofluorescence. A substantial proportion (5 to 10%) of lymphocytes in rat-activated T cells, which were prepared by transfer of Lewis strain thymocytes to Sprague-Dawley rats, formed rosettes with E'-rIgE, and essentially all of the RFC were stained by anti-T cell antibodies. The results indicated that a subset of human and rat T cells possess FcεR.
Evidence was obtained that FcεR on T cells are distinct from Fc receptors for IgG (FcγR), which were demonstrated by rosette formation with ox erythrocytes coated with rabbit IgG antibodies (EA). Mixed rosette assays showed that more than a half of FcεR-bearing human T cells failed to bind EA. Similarly, the majority of FcεR-bearing T cells in the lymph nodes of Nb-infected rats failed to bind EA. In activated T cell preparations, however, about three-fourths of FcεR-bearing cells formed mixed rosettes with EA, indicating that some T cells bear both FcεR and FcγR.
Accessory Cell Requirements for the Generation of Cytolytic T Lymphocytes
Authors: Lutz Charles T. , Fitch Frank W. 
Published: December 2022

Abstract
A system is presented that may simplify the study of accessory cell requirements for CTL generation. Cortisone resistant (CR) thymocytes containing alloreactive CTL precursors do not respond to allogeneic tumor cells unless non-T accessory cells are added to culture. In addition, splenic T cells do not respond to allogeneic tumor cells in the absence of non-T accessory cells. These accessory cells share several properties of macrophages.
Cytotoxic Thy 1.2-Positive Blasts with NK-Like Target Selectivity in Murine Mixed Lymphocyte Cultures
Authors: Kärre Klas , Seeley Janet K. 
Published: December 2022

Abstract
CBA × A/Sn spleen cells kept in H-2b allosensitized and control cultures (all containing 10% FCS) were assayed for cytotoxic activity in the 51Cr-release assay against YAC-1, an A/Sn-derived lymphoma that is highly sensitive to murine NK cells. After a decline during the first 24 hr of culture, anti-YAC-1 activity reappeared with a peak on day 3, thereafter it decreased to baseline levels as the allospecific activity (against RBL-5 H-2b lymphoma cells) peaked on day 5. This early, transient, anti-YAC-1 activity, termed “anomalous killing (AK)”, also occurred in control cultures, but was weaker and less reproducible there. With effectors from day 3 MLC, there was no cross-competition between the AK and the allospecific component in cold target inhibition experiments. The same effectors lysed human and murine semisyngeneic tumors in the same preferential order as fresh NK cells. The cells responsible for AK were nonadherent, nonphagocytic, of large size (sedimentation velocity &gt;6 mm/hr), and sensitive to treatment with monoclonal anti-Thy 1.2 antibodies + complement. In contrast, NK activity of fresh spleen cells was mediated by small lymphocytes and was not decreased by anti-Thy 1.2 treatment in parallel experiments. The AK may represent further differentiation of NK cells or activation of a mature T cell subset. The mechanism of activation in relation to the in vivo immune response and in vitro induced NK-like activity in human systems is discussed.
Modulation of Stimulated Phospholipid Metabolism in Mast Cells by Pharmacologic Agents That Increase Cyclic 3′,5′ Adenosine Monophosphate Levels
Authors: Kennerly Donald A. , Secosan Craig J. , Parker Charles W. , Sullivan Timothy J. 
Published: December 2022

Abstract
Phospholipid (PL) metabolism is markedly stimulated during mediator release from isolated rat mast cells. The present studies were performed to extend studies of the association of these PL reactions with the mediator release process and to probe the mechanisms by which pharmacologic agents that increase cyclic 3′,5′ adenosine monophosphate (cAMP) levels inhibit mediator release. Theophylline (1 to 20 mM) and N6, O2-dibutyryl cAMP (DBcAMP, 1 to 10 mM) markedly inhibited 32PO4 incorporation into phosphatidic acid (PA), phosphatidylinositol (PI), and phosphatidylcholine (PC) in unstimulated mast cells. Epinephrine (1 to 100 µM) had no effect on PL labeling in resting cells. The histamine release and increased 32PO4 labeling of PA, PI, and PC observed in mast cells stimulated by a goat anti-rat IgE antiserum were inhibited in parallel by theophylline (ID50 approximately 5 mM for all parameters) and by DBcAMP (ID50 approximately 3 mM for all parameters). Epinephrine (1 to 100 µM) did not modify mediator release or labeling of PA or PC, but did modestly inhibit PI labeling (23% inhibition at 100 µM epinephrine). Theophylline (above 3 mM) was found to arrest significantly ongoing mediator release and PL labeling when added as late as 2 to 5 min after anti-IgE challenge. The parallel effects of these pharmacologic interventions on mediator release and PL metabolism provide further evidence that the two processes are biochemically linked.
Expansion of Human Lymphocyte Populations Expressing Specific Immune Reactivities
Authors: Malissen Bernard , Charmot Dominique , Liabeuf Andre , Mawas Claude 
Published: December 2022

Abstract
Fourteen-day-primary MLR cultures, containing cells positively selected for the alloantigens of the stimulator, express the following immune reactivities: accelerated proliferation toward the specific stimulator or any allogeneic cell sharing with it HLA-D/DR antigens (PLT), strong specific cytotoxicity toward the stimulator cells (CML) or any cell sharing MHC products with it, and a strong inhibitory effect upon the proliferation in a fresh MLR of the original combination. Such primed cells can still proliferate when exposed to mitogenic doses of lectins. We have investigated whether, after a cycle of proliferation induced by mitogens, these cells could still express a specific immune reactivity such as CML. PHA, Con A, and PKW all induce a strong proliferation in primed cells, but only those primed cells stimulated by PKW were specifically cytotoxic. In contrast PHA- and Con A-stimulated cells had lost their lytic function. The absence of cytolytic function in primed cells stimulated by PHA is a complex phenomenon. Experiments where day 7 MLR cells were separated by 1 × G velocity sedimentation into blasts and small cells suggest a mitogen-dependent inhibitory effect upon CTL differentiation from day 7 blast cells, which requires cells that were small on day 7.
We have also observed a direct effect of PHA upon differentiated CTL: CTL incubated for as few as 2.5 hr in the presence of PHA lost 80% of their lytic potential, whether the incubation was done at 37 or 4°C. This effect was not seen after incubation with PKW. The effect of PHA is reversible: CTL function can be rescued provided the effector cells are cultured for at least 24 hr in the absence of PHA (with or without additional stimulator cells). In view of this reversible effect of PHA upon the expression of the lytic function by primed cells, we conclude that both PHA and PKW induce proliferation of the CTL clones included within the primed population, although after PHA (or Con A) stimulation the lytic function is not readily detectable. We propose provisionally to call the inhibitory effect of PHA and Con A an “eclipse” of the lytic function of primed cells.
Degranulation of Human Basophils: Quantitative Analysis of Histamine Release and Desensitization, Due to a Bivalent Penicilloyl Hapten
Authors: Dembo Micah , Goldstein Byron , Sobotka Anne K. , Lichtenstein Lawrence M. 
Published: December 2022

Abstract
We present a quantitative model of histamine release from human basophils due to the symmetric bivalent hapten, Bis benzylpencilloyl 1,6 diaminohexane, (BPO)2. The major elements of model are: 1) The histamine content of basophils is divided into a large number of discrete and quasi-independent “quanta.” 2) A certain fraction of the quanta in a population of basophils are nonreleasable. 3) Release of the contents of a quanta is a stochastic event. 4) The binding and cross-linking reaction between (BPO)2 and cell surface IgE approaches thermal equilibrium on a time scale that is very short compared to the time scale of histamine release from or desensitization of basophils. 5) The probability per unit time of the release event, PR, is a function of the extracellular calcium concentration [Ca]ex, and of the number of cross-linked IgE molecules per cell, Xpoly. In addition, the functional dependence of PR on Xpoly for fixed [Ca]ex is sigmoid, and the dependence of PR on [Ca]ex is such that PR → 0 as [Ca]ex → 0 for all values of Xpoly. 6) Antigen-specific IgE molecules and/or their associated Fc receptors are inactivated at a rate that is a saturable function of Xpoly. Furthermore, this process of inactivation is not dependent on the extracellular calcium concentration.
The model is tested by carrying out a detailed fitting to histamine release data obtained by using cells from a single donor. Good agreement between theory and experiment is obtained, and all the parameters of the model are determined. The ways in which the model can be extended to include systems more complex than the (BPO)2 system are briefly discussed.