bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characteristics of tolerance induction among adult hapten-specific T lymphocyte precursors revealed by clonal analysis.
Authors: Good M F , Nossal G J 
Published: December 2022

Abstract
Thaptens 2,4,6-trinitrobenzene sulfonic acid (TNBS) and 3-iodo-4-hydroxy-5-nitrophenyl-acetic acid succinamide ester (NIP) on murine splenic and thymic cytotoxic T lymphocyte precursors (CTLp) was studied. Both BALB/c (H-2d) and CBA (H-2k) CTLp can be rendered unresponsive to subsequent in vitro stimulation with either hapten, provided the mice were pretreated with the correct dose of reactive hapten. The unresponsiveness was shown not to be due to toxicity, because treated animals can mount an alloreactive response equivalent to untreated animals. A degree of cross-reactivity in tolerance induction, however, was demonstrated between the two different haptens. Limit dilution analysis of tolerant lymphoid populations reveals that such cells obey single hit (zero order) kinetics and that there is effective deletion of the CTLp. After correction for "anti-self" responses, the anti-TNP CTLp frequency in TNBS-treated BALB/c mice was 10.7 X 10(-6) in contrast to 101.1 X 10(-6) in control animals (89.4% tolerance). Similarly, after correction for "anti-self" responses, the anti-NIP CTLp frequency in NIP-treated animals was 4.7 X 10(-6), in comparison to 42.8 X 10(-6) in control animals (89.0% tolerance). Kinetic studies show that tolerance occurs within 24 hr. This, together with the limit dilution data, argues against the role of suppressor cells, over the cellular range studied.
A monoclonal antibody reactive with Marek's disease tumor-associated surface antigen.
Authors: Lee L F , Liu X , Sharma J M , Nazerian K , Bacon L D 
Published: December 2022

Abstract
An antibody-secreting hybridoma, RPH-6, to Marek's disease tumor-associated surface antigen (MATSA) was produced by somatic-cell hybridization between the mouse myeloma SP2/O-Ag/14 and spleen cells from MSB1 immunized mice. The antibody reacted with 95 to 100% of the cells from eight of 10 chicken MD cell lines and one of two turkey MD cell lines. It did not react with chicken MD cell lines RP1 and SK3, turkey MD cell line RP19, lymphoid leukosis (LL) cell lines, RP9 and RP12, and reticuloendotheliosis virus (REV) cell line RP14. A weak reaction was observed with REV cell line RP13 (10 to 20%), and a very slight reaction with normal chicken spleen cells (1 to 5%). RPH-6 produces immunoglobulin of the IgM class. Cell culture and mouse ascitic fluids have titers of 10(2) and 10(6), respectively, by fluorescent antibody (FA) test against MD tumor cell lines. The antibody did not react with Marek's disease virus (MDV) internal antigen or membrane antigen as detected by indirect FA test on chicken embryo fibroblast cultures grown on coverslips. The 51Cr release assay showed RPH-6 is highly cytotoxic (60% release) only against MD lymphoblastoid cell lines, with antibody prepared from mouse ascites having a cytotoxic titer approaching 10(6). Results from using RPH-6 for differential diagnosis of chicken lymphoid tumors of unknown origin were in complete agreement with those obtained with rabbit anti-MATSA reference serum and pathologic diagnosis.
Level of mIa expression on mitogen-stimulated murine B lymphocytes is dependent on position in cell cycle.
Authors: Monroe J G , Cambier J C 
Published: December 2022

Abstract
Using correlated flow cytometric analysis of cell surface Ia antigen expression (immunofluorescence) and cell cycle phase (pulse-width of axial light extinction), we have quantitated changes in expression of mIa antigen on murine B cells during progression through cell cycle. Our results indicate that density of mIa expressed on mitogen-stimulated B cells increases fourfold to fivefold during the transition from G0 to G1. By early S phase, mIa density has decreased by fourfold to fivefold relative to peak expression. This decrease becomes more evident by late S, G2, and M phases, when an eightfold decrease in mIa antigen density is observed relative to peak levels. This decrease results in mIa antigen expression lower than that of resting, unstimulated B cells. Therefore, maximum mIa antigen expression occurs during G0 to G1 transition and in early G1, when a requirement for I region-restricted, antigen-driven T cell help for thymus-dependent, antigen-driven B cell activation has been demonstrated.
Bone marrow-derived macrophage as accessory cells in antigen-induced T cell proliferation. H-2I region requirements for L-glutamic60-L-alanine30-L-tyrosine10 response.
Authors: Schook L B , Allen P M , Niederhuber J E 
Published: December 2022

Abstract
Marrow stem cells cultured with L cell-conditioned medium were used to produce large numbers of macrophages free of contaminating lymphoid cells or granulocytes. Experiments were performed by using these bone marrow-derived macrophages (BMDM) as antigen-presenting cells (APC) for the terpolymer antigen L-glutamic60-L-alanine30-L-tyrosine10 (GAT). By using antigen-specific T cell proliferation, it was demonstrated that BMDM were equal to splenic macrophages in their capacity to present GAT. Furthermore, when BMDM were pretreated with alloantibodies specific for Ia antigens of the I-A subregion, the T cell proliferative response to GAT was inhibited. The I-A subregion is known to be the site of Ir gene regulation of the GAT response, and antibodies to other subregions had no inhibitory effect. Monoclonal antibodies recognizing a beta-chain product of the I-A subregion (Ia. 17) also inhibited the BMDM from effective antigen presentation. These results were similar to those obtained with purified splenic macrophages.
The effect of alpha 1 antitrypsin on the proliferative response of human peripheral blood lymphocytes.
Authors: Breit S N , Luckhurst E , Penny R 
Published: December 2022

Abstract
In evaluating immune aberrations in patients with alpha 1 antitrypsin (alpha 1 AT) deficiency, we have previously shown that they exhibit enhanced lymphocyte responsiveness to PHA that is serum mediated. In this study, we demonstrate suppression of the PHA response by using purified alpha 1 AT, and also similar but less marked suppression of the Con A response. alpha 1 AT, however, has no effect whatsoever on PWM-induced proliferation. This effect is demonstrable provided alpha 1 AT is added within 4 hr of mitogen activation and is mediated by its action on adherent cells rather than on proliferating lymphocytes. Adherent cells still exhibit this effect if pulsed with alpha 1 AT, then thoroughly washed before their activation. This suggests that it may be inhibiting a membrane serine esterase already activated before the addition of PHA. Thus alpha 1 AT may modulate the activation of T cells through its effect on monocytes, leading to abnormalities in immunoregulation, and hence a predisposition to the development of a variety of immunologic disorders in alpha 1 AT-deficient subjects.
Autoimmune effector cells. IV. Induction of experimental allergic encephalomyelitis in Lewis rats without adjuvant.
Authors: Holda J H , Silberg D , Swanborg R H 
Published: December 2022

Abstract
Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats without the aid of adjuvant. Radioresistant cells were activated from spleens of nonimmune donor rats by in vitro culture with myelin basic protein (BP). After adoptive transfer, these cells recruited EAE effector cells in normal syngeneic recipients, as demonstrated after transfer to secondary hosts. The induction of EAE without adjuvant may lead to a better understanding of the mechanisms of autoimmune disease induction.
Identification of a membrane antigen that is distinct from the interleukin 2 receptor and that may be required for interleukin 2-driven proliferative responses.
Authors: Malek T R , Robb R J , Shevach E M 
Published: December 2022

Abstract
During the course of studies designed to raise murine monoclonal antibodies to a guinea pig alloreactive T cell line, an IgM monoclonal antibody (5C3) was identified that completely inhibited the alloantigen and IL 2-dependent proliferative response of the immunizing colony and other alloreactive T cell colonies with different antigen specificities. Tissue distribution on the FACS demonstrated that the surface antigen defined by 5C3 was preferentially expressed on T cells activated by mitogen, alloantigen, or antigen. 5C3 was also a potent inhibitor of alloantigen- and antigen-induced T cell proliferation. In addition, 5C3 substantially inhibited the proliferative response of guinea pig Con A-induced blast cells to guinea pig IL 2-containing culture fluids and to a preparation of partially purified human IL 2 but was a poor inhibitor of mitogen-induced T cell proliferation. Blast cells obtained from the co-culture of mesenteric lymph node cells with Con A in the presence of 5C3 lacked the surface molecule defined by 5C3. The 5C3- and 5C3+ blast populations, nevertheless, absorbed equivalent amounts of IL 2, which suggested that 5C3- blasts were not deficient in the expression of IL 2 receptors. However, 5C3- blast cells failed to proliferate in response to IL 2-containing culture fluids. Furthermore, 5C3 had no inhibitory activity on either the binding or subsequent degradation of radiolabeled human IL 2 by guinea pig IL 2 receptors. These data suggest that 5C3 recognizes a component of a putative IL 2 receptor-effector complex distinct from the IL 2 receptor and that this molecule plays a critical role in the processing or generation of the growth signal IL 2 transmits to T lymphocytes.
A requirement for nonspecific T cell factors in antibody responses to "T cell independent" antigens.
Authors: Endres R O , Kushnir E , Kappler J W , Marrack P , Kinsky S C 
Published: December 2022

Abstract
Using murine splenic B cell preparations depleted of macrophages and rigorously depleted of T cells, we studied the role of nonspecific helper factors in in vitro antibody responses to T cell-independent (TI) type 1 and type 2 antigens. TNP-lipopolysaccharide, TNP-Brucella abortus, and DNP-liposomes containing lipid A were chosen as examples of TI type 1 antigens. DNP-Ficoll and DNP-liposomes without lipid A were chosen as TI type 2 antigens. Only the type 1 antigens were able to elicit significant, albeit very weak, responses without added helper factors. Both type 1 and 2 antigens required factors present in supernatants from concanavalin A-stimulated spleen cells (Con A SN) to stimulate optimum antibody responses. Interleukin 2- (IL 2) containing supernatant from the T cell hybridoma FS6-14.13 supported suboptimal responses to varying degrees with each TI antigen, in contrast to its lack of effect on responses to sheep red blood cells in the absence of additional factors. This activity of the FS6-14.13 supernatant was removed by absorption with the IL 2-dependent T cell line HT-2, suggesting that IL 2 was the active component. Another factor, IL-X, which is distinct from both IL 1 and IL 2 and is also found in Con A SN, was required in addition to IL 2 to achieve optimal responses with both types of TI antigens. These results clearly establish a role for factors derived from T cells in the activation of B cells by both type 1 and type 2 TI antigens.
Nonspecific inhibitor of DNA synthesis elaborated by T acceptor cells. I. Specific hapten- and I-J-driven liberation of an inhibitor of cell proliferation by Lyt-1-2+ cyclophosphamide-sensitive T acceptor cells armed with a product of Lyt-1+2+-specific suppressor cells.
Authors: Malkovský M , Asherson G L , Chandler P , Colizzi V , Watkins M C , Zembala M 
Published: December 2022

Abstract
Lyt-1+2+ hapten-specific T suppressor cells (Ts) from mice injected and then painted with picryl or oxazolone derivatives produce hapten-specific T suppressor factors (TsF) in vitro. Stimulation by painting with contact sensitizer (which need not be specific) gives rise to Lyt-1-2+, I-J+, cyclophosphamide-sensitive T acceptor cells (Tacc). When the Tacc population is armed with TsF and then is exposed to specific antigen in the context of I-J-controlled determinants (antigen-presenting, haptenized spleen cells and Ts sharing the same I-J subregion), a nonspecific inhibitor of DNA synthesis (nsINH) appears in the supernatant. This inhibitor suppresses the primary DNA synthetic response to concanavalin A, lipopolysaccharide, and alloantigens in both syngeneic and allogeneic lymphocytes. The nsINH is only effective when added to lymphocyte cultures less than 8 hr after the stimulation with concanavalin A. The nsINH, however, affects neither primary nor secondary cytotoxicity in vitro. These data suggest the mouse immune system is capable of selective regulation of the response to specific antigen by the production of nonspecific soluble suppressor factor(s).
The synthesis and secretion of granulocyte-monocyte colony-stimulating activity (CSA) by isolated human monocytes: kinetics of the response to bacterial endotoxin.
Authors: Sullivan R , Gans P J , McCarroll L A 
Published: December 2022

Abstract
We studied the kinetics of the synthesis and secretion of granulocyte-monocyte colony-stimulating activity (CSA) by human monocytes stimulated by S. typhi endotoxin. We found that these cells initially secrete copious quantities of CSA when exposed to endotoxin but rapidly become refractory to its stimulatory effect. When monocytes were incubated in liquid suspension cultures, large amounts of CSA were generated during the first 24 hr of culture after the addition of as little as 10 ng/ml of endotoxin to previously unstimulated monocytes. After the addition of endotoxin, CSA secretion abruptly took place after an initial 1 to 2 hr lag phase, and occurred primarily within the first 6 to 12 hr of culture. The addition of puromycin or cycloheximide to the cultures significantly inhibited CSA secretion in response to endotoxin, suggesting that CSA production by stimulated monocytes requires de novo protein synthesis and does not solely result from the release of preformed active CSA. After initial exposure to endotoxin, CSA production by monocytes steadily decreased after 24 hr and ceased after 72 hr. Subsequent reexposure to the same concentration of endotoxin resulted in little CSA production, whereas the refractory state could be overcome by increasing the quantity of endotoxin added. Additional studies demonstrated that refractoriness of monocytes to further CSA production after initial response to endotoxin was not due to a loss of cell viability, degradation of endotoxin, or inhibition of CSA synthesis by soluble metabolites generated by stimulated monocytes. Our data suggest that the capacity of human monocytes to synthesize CSA in response to endotoxin rapidly becomes blunted after initial exposure of the cells to the lipopolysaccharide, but that the refractory state of these cells can be overcome by increasing the concentration of endotoxin. Acquired hyporesponsiveness of cells that produce CSA may in part account for the phenomenon of immediate endotoxin tolerance observed in vivo.
Isoelectric focusing of human anti-diphtheria toxoid antibodies: identical spectrotypes of anti-fragment A antibodies with the same IgG subclass and light chain constant regions are expressed in multiple individuals.
Authors: Morrow C D , Dorey F , Stevens R H 
Published: December 2022

Abstract
The serum antibodies from humans booster-immunized with diphtheria toxoid were analyzed by isoelectric focusing. To restrict the antibody response, we visualized those antibodies that reacted to the Fragment A moiety of diphtheria toxin. Of the 100 normal human donors examined, 20 were estimated to be nonresponders to Fragment A. Sixty-three of the 80 donors who responded to Fragment A had restricted IgG-anti-Fragment A spectrotypes that consisted of three to eight distinct bands. Six series of repeat or shared spectrotypes were delineated among our donor population with repeat frequencies ranging from 0.025 to 0.312. We determined that the repeat spectrotypes were IgG1-kappa anti-Fragment A antibodies. Three percent of our donors had complex IgG-anti Fragment A spectrotypes consisting of greater than 10 bands. In some instances, the complex spectrotypes were composed of simple spectrotypes found among other donors. The complex IgG-anti Fragment A spectrotypes of these donors consisted of both IgG1 and IgG4-anti-Fragment A antibodies. From a statistical analysis, we calculate that only a limited number of IgG-anti-Fragment A spectrotypes are expressed in vivo after booster immunization. Our analysis suggests two groups of IgG-anti-Fragment A spectrotypes exist in our donor population. One IgG-anti-Fragment A spectrotype group is expressed randomly, and a second group is preferentially expressed among individuals in our donor population.
Cell volume and osmotic properties of erythrocytes after complement lysis measured by flow cytometry.
Authors: Bauer J , Valet G 
Published: December 2022

Abstract
The changes of volume distribution curves of erythrocytes during and after lysis by complement or nystatin or in hypotonic buffers were measured by flow cytometry. Biconcave and spheroidal ghosts were observed after complement lysis and spheroidal ghosts were seen only after nystatin and hypotonic lysis. The spheroidal ghosts derived from red cells lysed by complement or nystatin were permeable to sucrose; those from hypotonic lysis were sucrose-impermeable. Spheroidal ghosts after complement lysis remained permeable for sucrose whereas spheroidal ghosts after nystatin lysis resealed after removal of the drug by washing. Biconcave ghosts produced by complement lysis were almost impermeable to sucrose initially and therefore responded to osmotic changes, but they became sucrose-permeable upon prolonged incubation at 37 degrees C. The rate of sucrose equilibration increased as the stability of the biconcave shape diminished with increasing numbers of C5b-9 complexes. At 850 C5b-9 complexes/ghost, the biconcave shape and impermeability for sucrose were completely lost. The results support the hypothesis that complement C5b-9 complexes, in addition to the interaction with the lipid bilayer, may interact with the cytoskeleton of the erythrocyte membrane.
Studies on the mechanism of bacterial resistance to complement-mediated killing. III. C5b-9 deposits stably on rough and type 7 S. pneumoniae without causing bacterial killing.
Authors: Joiner K , Brown E , Hammer C , Warren K , Frank M 
Published: December 2022

Abstract
Gram-positive cocci resist direct killing by serum. The mechanism of resistance was studied by measuring consumption of terminal complement components from serum and uptake of purified, radiolabeled C7 and C9 on rough and encapsulated type 7 Streptococcus pneumoniae. Extensive consumption of C5, C7, and C9 occurred when 5 X 10(8) rough or type 7 pneumococci were incubated for 1 hr in 10% pooled normal human serum (PNHS). Approximately 10,000 molecules of C7 and C9 bound per organism during the same period of incubation. Twenty to 30% of C7 and C9 was released from rough organisms. Release was not due to autolysis since it occurred with glutaraldehyde-fixed organisms as well as in S. pneumoniae that were rendered resistant to autolysis by growth in ethanolamine. Between 10 and 30% of bound 125IC9 counts were eluted from the rough and type 7 organisms by incubation in 1 M NaCl or 0.01 M EDTA, which suggests that bound C5b-9 was not attached by predominantly ionic interactions. Elution of 44 to 74% of 125IC9 from live and glutaraldehyde-fixed organisms by 1% sodium deoxycholate suggests that hydrophobic bonds are involved in C5b-9 attachment. Trypsin cleaved 67 and 55% of 125IC9 counts from live rough and type 7 S. pneumoniae, respectively which indicates that the bound complex is not protected by the cell wall from proteolytic attack. Serum resistance in S. pneumoniae does not represent a failure to form C5b-9 on the bacterial cell wall but apparently reflects a failure of the bound complex to penetrate the thick peptidoglycan layer.
Granulocyte activation by endotoxin. II. Role of granulocyte adherence, aggregation, and effect of cytochalasin B, and comparison with formylated chemotactic peptide-induced stimulation.
Authors: Dahinden C , Fehr J 
Published: December 2022

Abstract
PMN stimulation by endotoxin is heavily dependent on incubation conditions: although marked increase of PMN adhesiveness, enzyme release, and hexose monophosphate shunt activity, as well as superoxide production, occur when endotoxin-challenged cells are incubated in stationary petri dishes, absolutely no such response is observed with cells kept in suspension. Preincubation with cytochalasin B does not alter this reaction pattern. Hyperadhesiveness of endotoxin-challenged PMN is retained after thorough washing, eliminating the possibility that adhesion is due to absorption of endotoxin to petri dishes. In contrast to formylated chemotactic peptides that stimulate PMN adherence as well as aggregation, endotoxin elicits absolutely no aggregatory response (+/- cytochalasin B). Preexposure to endotoxin does not block the aggregatory response to subsequent addition of chemotactic peptides, whereas effects of endotoxin and formylated peptides on PMN in the stationary system are additive. These findings indicate that contact to surfaces is an essential primary event in PMN stimulation.
Studies of allogeneic tumor transplants: induced rejection of advanced tumors by immune alteration of recipients.
Authors: Russell P S , Chase C M , Burton R C 
Published: December 2022

Abstract
In the present experiments, a methylcholanthrene-induced sarcoma (S-702) of B10.D2 origin was found to grow rapidly in B6AF1 mice leading to the death of all recipients in 5 to 9 wk. Nevertheless, immunity to MHC antigens presented by the tumor was readily demonstrable in tumor-bearing mice by their responses to donor strain skin grafts until late in the course of tumor growth, when a nonspecific form of immune suppression developed. In addition, B6AF1 mice preimmunized by exposure to B10.D2 donor strain antigens did not permit tumor growth. Treatment of tumor-bearing B6AF1 mice with CY at 18 days, when the tumors measured over 12-mm in diameter, followed by the i.p. injection of B10.D2 lymphoid cells (at a dosage of from 1.2 to 2.5 X 10(8) cells) resulted in the complete regression of 100% of these large tumors. CY treatment combined with localized immune stimuli in the form of donor strain skin grafts or secondary tumor implants was incapable of producing a sufficiently heightened immune response to cause tumor rejection. A dose of CY temporarily retarded tumor growth in most mice, and in a minority of animals so treated (less than 25%) tumors regressed completely. In syngeneic (B10.D2) animals, CY also temporarily slowed tumor growth, but total regression was never observed. An effective B10.D2 cell inoculum could consist not only of living lymphoid cells but of irradiated (1000 rad) cells as well. Tumor cell suspensions (after irradiation, 10,000 rad) were also effective. These observations suggest local immune factors at the host-tumor interface may have been of importance in the survival of these allogeneic tumor transplants and that CY influenced this state, perhaps through an influence on suppressor cells, allowing subsequent administration of donor strain cellular antigens to induce an effective tumor rejection response.