bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural Cytotoxic Cells against Solid Tumors in Mice
Authors: Stutman Osias , Paige Christopher J. , Figarella Elizabeth Feo 
Published: December 2022

Abstract
Lymphohemopoietic cells from normal mice show cell-mediated cytotoxicity (CMC) against syngeneic or allogeneic chemically induced fibrosarcomas, when tested in a 24-hr cytotoxicity assay with 3H-proline pre-labeled adherent target cells. When two BALB/c tumors, Meth A, and Meth 113 were studied, spleen cells from syngeneic normal donors showed high CMC against Meth A and no CMC toward Meth 113. However, Meth 113 was susceptible to natural CMC by spleen cells from other mouse strains or PHA-induced CMC by syngeneic spleen cells. Other solid tumors tested showed variable patterns of susceptibility-resistance to natural CMC, whereas normal fibroblasts were negative. Susceptibility to natural CMC does not correlate with expression of murine leukemia virus-related antigens. Established lines are more susceptible to natural CMC than secondary tumor cultures, although susceptibility-resistance appear as stable properties of the targets. All the mouse strains and sublines tested showed natural CMC against the Meth A target; however, only a few strains (A/J, CBA/HN, NZB, and C3H/He) showed natural CMC against Meth 113. Natural CMC against Meth 113 of (BALB/c × A/J) F1 spleen cells is dominant, and the hybrid behaves like the reactive A/J parent. Natural cytotoxic (NC) cells are detected in nude mice in a BALB/c or CBA/H background (and also in CBA/HN mice, which have a B cell defect). The tissue distribution of NC cells shows high activity in spleen and marrow, with lower activity in lymph nodes, peritoneal washings, and thymus. Peritoneal exudates induced by complete Freund's adjuvant or BCG show high NC cell activity. NC activity in spleen was detected from birth and does not seem to decay with age (even at 1 or 2 years of age). The described characteristics of the NC cell have some similarities (and some discrepancies) with the natural killer (NK) cell described against T lymphoma targets. The differences include: 1) strain distribution; 2) appearance at birth; 3) no decay with age, and 4) to some extent, tissue distribution (i.e. both systems show high activity in spleen; however, NC cells are detected in thymus whereas NK cells are not). The similarities include: 1) susceptibility not related to expression of murine leukemia virus antigens; 2) no H2 restriction of cytotoxicity; 3) activity present in nude mice (and CBA/HN); 4) reactivity dominant in F1 hybrids, and 5) increase activity in peritoneal exudates after BCG administration. It seems possible that these systems may act as anti-tumor surveillance devices.
Tumor-Associated Antigens of Rat Moloney Sarcoma Cells
Authors: Leung Kiu , Jones Joe M. , Feldman Joseph D. 
Published: December 2022

Abstract
The dissociated cell surface membranes of a rat Moloney sarcoma (MST), derived from a BN rat, were extracted with 2 M KI, with 6 M guanidine thiocyanate, or by papain digestion. Extracts obtained with these three reagents were fractionated on columns of controlled-pore glass, 170 Å pore size. A fraction was eluted from each preparation that contained tumor-associated antigens (TAA), viral, fetal, and histocompatibility antigens. With an antibody specific for TAA, the TAA, devoid of detectable viral, fetal, and histocompatibility antigens, were co-precipitated by addition of goat antibody to rat immunoglobulin. After electrophoresis, on slab gels, three bands were detected with estimated m.w. of 185,000, 150,000, and 70,000. No such bands were detected on slab gel electrophoresis with extracts of BC5, a chemically induced tumor, of normal BN lymphoid cells, of M-MuLV, or of fetuses, after incubation with anti-TAA antibody and goat antibody to rat immunoglobulin. TAA extracts prepared with 2 M KI, 6 M guanidine thiocyanate, or papain digestion showed immunologic reactivity. Cold TAA inhibited the co-precipitation of labeled TAA by rat antibody specific for TAA; they elicited antibody in guinea pigs but not in rats; and antibodies specific for TAA were cytotoxic to MST in the presence of C.
Micro-Leukocyte Adherence Inhibition
Authors: Russo Anthony J. , Howell John H. , Leveson Stephen H. , Douglas Holyoke E. , Goldrosen Martin H. 
Published: December 2022

Abstract
To study the cellular basis for specific antigen-induced leukocyte adherence inhibition, enriched populations of B cells, T cells, and monocytes were prepared by a two-stage adherence separation procedure from spleen cells of normal C57BL/6J mice and mice bearing progressively growing MCA-38 tumors. The reactor cell undergoing specific antigen-induced adherence inhibition was identified as a monocyte (esterase positive, did not respond to mitogens, and did not bear Thy 1.2 antigen or surface immunoglobulin). Furthermore, an enriched population of MCA-38 sensitized B cells could program normal monocytes to undergo specific antigen-induced adherence inhibition. This programming could be abolished by pretreatment of the MCA-38 sensitized B cells with anti-immunoglobulin and complement (indirect cytotoxicity method). In contrast, enriched populations of MCA-38 sensitized T cells could not program normal nylon wool adherent cells to undergo antigen-specific adherence inhibition; and anti-Thy 1.2 serum and complement had no effect on specific antigen-induced adherence inhibition. Thus, in this murine tumor model, leukocyte adherence inhibition appears to be due to the programming of monocytes by sensitized B cells.
Specific Inhibition of Cytotoxic Memory Cells Produced against UV-Induced Tumors in UV-Irradiated Mice
Authors: Thorn Richard M. 
Published: December 2022

Abstract
Cytotoxic responses of UV-irradiated mice against syngeneic UV-induced tumors were measured by using a 51Cr-release assay to determine if UV treatment induced a specific reduction of cytotoxic activity. The in vivo and in vitro primary responses against syngeneic tumors and allogeneic cells were unaffected, as was the “memory” response (in vivo stimulation, in vitro restimulation) against alloantigens. In contrast, the memory response of UV-treated mice against syngeneic, UV-induced tumors was consistently and significantly depressed. The cytotoxicity generated by tumor cells stimulation in vivo or in vitro was tumor-specific and T cell-dependent. Since the primary response against syngeneic UV-induced tumors produces apparently normal amounts of tumor-specific cytotoxic activity, UV-treated mice may not reject transplanted syngeneic tumors because of too few T effector memory cells. These results imply that, at least in this system, tumor rejection depends mostly on the secondary responses against tumor antigens and that at least one carcinogen can, indirectly, specifically regulate immune responses.
Immunologic Functions of Ia-Bearing Epidermal Langerhans Cells
Authors: Stingl Georg , Katz Stephen I. , Clement Loran , Green Ira , Shevach Ethan M. 
Published: December 2022

Abstract
Langerhans cells (LC) constitute a morphologically well-characterized minor subpopulation of the mammalian epidermis whose functional role is still a matter of conjecture. The hypothesis that LC represent an epidermal equivalent to cells of the monocyte-macrophage-histiocyte series is supported by the recent observations that in humans and guinea pigs LC are the only epidermal cells that express Fc-IgG receptors, C3 receptors, and Ia antigens. Using inbred strain 2 and strain 13 guinea pigs, we investigated in this study whether LC can mediate the same immunologic functions as Ia-bearing macrophages. LC-enriched and LC-depleted epidermal cells were prepared by separation of Fc-IgG rosetting epidermal cells on density gradients. When both populations were tested for the biosynthesis of alloantigens by immunoprecipitation techniques, Ia antigen synthesis was restricted to the LC-enriched fraction. Functional studies demonstrated that antigen-pulsed LC-enriched epidermal cells induce a proliferative response in immune T cells that is comparable in magnitude to that seen with macrophages. Moreover, effective presentation of immunologically relevant antigen requires syngeneity between LC-enriched epidermal cells and responder lymphocytes. In the mixed leukocyte reaction (MLR), LC-enriched epidermal cells were as effective stimulators as macrophages. LC-depleted epidermal cells, by contrast, induced little or no stimulation in both assay systems. Both the antigen-presenting and the MLR-stimulatory capacities of LC-enriched epidermal cells could be abrogated by pretreatment with anti-Ia sera and complement. The presence in the epidermis of Ia-bearing LC, capable of mediating the immunologic functions of Ia-bearing macrophages, has important clinical implications with regard to the role of LC as sensitizing cells in both contact hypersensitivity and skin graft rejection.
Differential Effect of Neonatal Injections of Anti-µ or Anti-δ Antibodies on the Synthesis of IgM, IgD, IgE, IgA, IgG1, IgG2a, IgG2b, and IgG2c Immunoglobulin Classes
Authors: Bazin Herve , Platteau Bernadette , Beckers Andree , Pauwels Romain 
Published: December 2022

Abstract
The effect of neonatally initiated injections of anti-µ or anti-δ antibodies on IgM, IgD, IgA, IgE, IgG1, IgG2a, IgG2b, and IgG2c immunoglobulin subclasses are described. As in chickens and mice, anti-µ suppression was demonstrated to be effective on rat IgM, IgA, and IgG classes but also on IgD and IgE classes and on the four subclasses of IgG. The anti-δ suppression clearly affected the IgD synthesis but also that of IgE. The different IgG subclasses were more or less diminished, but, on the contrary, the IgG2c serum level from day 55 on was largely increased. The IgM and IgA synthesis both were slightly affected with respect to their serum levels but significantly at the membrane level.
Rats suppressed by anti-µ or anti-δ sera were unable to build up a reaginic immune response taken as an example of T-dependent immune response.
The anti-µ suppression on all the immunoglobulin classes confirms that the IgM receptors are the first to appear on the precursors of the B lymphoid cells. The IgD suppression also confirms that the majority of B lymphoid cells carry IgD receptors during their maturation. Moreover, the absence of reaginic immune response indicates that the lack of the IgD receptor can make animals unable to produce primary IgE immune response.
The IgD receptor may be considered as an unspecific isotype-positive signal necessary for the majority of the B lymphoid cells to react for the first time to a specific antigen stimulation. The differential results of the anti-δ suppression, contrary to the general suppression obtained by the anti-µ inoculation, could be explained by the more or less important requirement by each isotype cell line, to be stimulated primarily by an antigen with the help of IgD class receptors.
An Attempt to Raise Antibodies against 2-O-α-D-Galactopyranose, the Disaccharide Unit of Collagen
Authors: Ebisu Shigeyuki , Garegg Per J. , Iversen Tommy , Goldstein Irwin J. 
Published: December 2022

Abstract
The p-isothiocyanatophenyl β-glycoside of 2-O-α-D-glucopyranosyl-D-galactopyranose, the disaccharide unit of collagen, was coupled to bovine serum albumin for use as an artificial antigen. The conjugate precipitated with concanavalin A but not with the Ricinus communis lectin. Rabbit antisera raised against the conjugate were characterized by immunodiffusion, quantitative precipitation, and hapten inhibition. After absorption with bovine serum albumin the antisera exhibited a specificity for the introduced p-isothiocyanatophenyl 2-O-α-D-glucopyranosyl-β-D-galactopyranoside. The relative importance of an α-configuration and the ordered sequence of the two sugars for binding to antibody were observed. The antibody-combining site was shown to involve the aglycone portion of the introduced hapten. 5-O-(2-O-α-D-glucopyranosyl-O-β-D-galactopyranosyl)-hydroxylysine and 5-O-(2-O-α-D-glucopyranosyl-O-β-D-galactopyranosyl)-hydroxylysine peptide, the glycopeptide unit in collagens, were poor inhibitors of the conjugate-antibody precipitation system. However, acetylation of the ε-amino groups of the hydroxylysyl residues converted these noninhibitory substrates into considerable inhibitors, suggesting that a charged -NH3+ group may interfere with binding of the haptenic groups to antibody.
Modulation of the Antigenicity of C1r̅ and C1s̅ by C1̄ Inactivator
Authors: Ziccardi Robert J. , Cooper Neil R. 
Published: December 2022

Abstract
The first complement component, C1, was activated in normal human sera by addition of aggregated IgG, immune complexes, and lipopolysaccharide, after which the concentrations of the C1 subcomponents, C1r and C1s, were measured by single radial immunodiffusion. A progressive reduction in C1r antigen content was observed as greater amounts of activator were added to normal human sera. Three lines of evidence proved that the apparent disappearance of C1r was due to interaction of C1r̅ with C1̄ Inactivator (C1̄ In). First, no loss of C1r antigen was detected in sera from patients with hereditary angioneurotic edema, which lack functional C1̄ Inactivator. Second, reconstitution of these patients' sera with physiologic concentrations of purified C1̄ In resulted in the disappearance of C1r antigen. Third, purified C1̄ In greatly reduced the intensity of the precipitin line formed between purified C1r̅ and anti-C1r̅.
In parallel experiments, certain antisera to C1s were found to show a comparable disappearance of C1s antigenic content in activated human sera. This antigenic loss was similarly shown to be due to the interaction of C1s̅ with C1̄ In. However, it should be noted that the detection of changes of C1s̅ antigenicity was dependent on the specificity of the C1s antisera employed, since antisera with antigenic specificities apparently directed to determinants on the C1s molecule distant from the region of interaction with C1̄ In did not show changes with activation.
Ultracentrifugal studies demonstrated that C1r̅ and C1s̅ formed soluble complexes with C1̄ In in activated serum, thus precluding the possibility that C1r̅ and C1s̅ escape immunochemical detection in activated serum by being present in large aggregated complexes. Also ruled out, in the case of C1s̅, is the possibility that the binding of C1̄ In leads to a major conformational rearrangement of C1s̅ with resulting changes in exposed antigens of the molecule. It is most likely that the loss in C1r̅ and C1s̅ antigenic content with activation of C1 in serum occurs because of simple physical masking of the relevant antigens of C1r̅ and C1s̅ by the relatively large C1̄ In molecule.
β-Estradiol Reduces Natural Killer Cells in Mice
Authors: Seaman William E. , Blackman Marcia A. , Gindhart Thomas D. , Roubinian Jirayr R. , Loeb John M. , Talal Norman 
Published: December 2022

Abstract
β-estradiol was administered to mice continuously by diffusion from a silastic tube that was implanted subcutaneously at 4 weeks of age. Four to 6 weeks of estrogen administration caused a substantial reduction in natural killer cell activity in the spleens from mice of either sex. Androgen (5α-dihydrotestosterone) did not. Castration of male or female mice did not affect natural killing and did not alter the effect of β-estradiol. Estradiol did not affect natural killing in vitro and the loss of natural killing was not due to a soluble or a cellular suppressor of natural killing. The effects of estradiol were not dependent on the thymus, since estradiol reduced natural killing in mice that had been neonatally thymectomized. After removal of the estrogen implant, natural killing recovered over a period of 8 weeks. The loss of natural killing may reflect a loss of bone marrow secondary to estrogen-induced osteosclerosis.
Autoantibody to a Nuclear Antigen in Proliferating Cells
Authors: Miyachi Kiyomitsu , Fritzler Marvin J. , Tan Eng M. 
Published: December 2022

Abstract
This study reports the identification of an autoantibody in the sera of some patients with systemic lupus erythematosus that reacted with nuclear antigen(s) of proliferating cells. The autoantibody was initially detected by the observation that it did not react in immunofluorescence with nuclei of renal tubular or glomerular cells, nor with hepatic parenchymal cells, but only reacted with scattered cells in the interstitial tissue of these two organs. In contrast, many lymphocytes in lymph node follicles, spleen, and thymus reacted with this antinuclear antibody. Normal peripheral blood lymphocytes did not show nuclear staining but after mitogenic stimulation, 20% of cells became positive. Nuclear staining was not restricted to lymphocytes but was also observed in several tissue culture cells lines such as Hep-2 cells (human epithelial carcinoma), Ehrlich ascites tumor cells, and baby hamster kidney cells. The reactive nuclear antigen(s) was soluble in physiologic saline and reacted with serum autoantibody to give a precipitin line in immunodiffusion that was immunologically distinct from DNA and other known nuclear antigen-antibody precipitating systems. Autoantibodies to proliferating cell nuclear antigen(s) might serve as useful biologic markers to study stimulated lymphocytes and other proliferating cells.
Macrophage-T Cell Interactions in the Con A Induction of Human Suppressive T Cells
Authors: Raff Howard V. , Cochrum Kent C. , Stobo John D. 
Published: December 2022

Abstract
Macrophage-T interactions are required for the Con A-induced generation of human Ts capable of inhibiting PHA-induced blastogenesis among autologous PBMC. Con A treatment of adherent cell-depleted PBMC, or PBMC recovered after a 7-day incubation in FCS, failed to generate Ts. Addition of adherent cells to either of these populations restored Con A inducible Ts. Discontinuous density gradient fractionation of adherent cells demonstrated that the required accessory cell was a low density macrophage bearing the human equivalent of murine Ia.
A New B Cell Differentiation Antigen (BDA) on Normal and Leukemic Human B Lymphocytes That Is Distinct from Known DR (Ia-Like) Antigens
Authors: Balch Charles M. , Dougherty Patricia A. , Vogler Larry B. , Ades Edwin W. , Ferrone Soldano 
Published: December 2022

Abstract
A newly defined human B cell differentiation antigen, designated as BDA, has been defined and partially characterized. BDA is expressed on normal human B cells and lymphocytic leukemia cells at all stages of known differentiation (pre-B cells to plasma cells). It is distinct from DR (Ia-like) determinants and other known B cell surface constituents.
Genetic Identification of a Locus Linked to the Rat MHC That Codes for a Membrane Antigen Detectable with Cytotoxic Lymphocytes
Authors: Lynch David H. , Dewitt Charles W. 
Published: December 2022

Abstract
Cell-mediated cytolytic (CMC) responses resulted from immunizations between rat strains purported to be identical at Ag-B, the major histocompatibility complex (MHC), but differing at other loci not linked to Ag-B. In vivo-priming followed by secondary in vitro stimulation was required to generate a measurable CMC response as determined by a 51Cr-release assay. Neither in vivo nor in vitro stimulation alone was adequate. The CMC responses generated in a strain combination considered Ag-B identical (LEW·B3:BN) were specific for a determinant controlled by a gene linked to Ag-B, which has been designated Ag-L. The CMC response appears not to be restricted to syngeneity at Ag-B. In addition, the data presented demonstrate a recombinant between Ag-B and Ag-L, and suggest that the gene has failed to transfer with the MHC during the isolation of the LEW·B3 and F-344·B3 congenic strains.
Specificity Studies on the Proliferative Response of Thymus-Derived Lymphocytes to Influenza Viruses
Authors: Butchko Gregory M. , Armstrong Robert B. , Ennis Francis A. 
Published: December 2022

Abstract
Studies were undertaken to characterize the lympho-proliferative response to primary influenza virus infection and to determine the specificity of antigenic recognition by proliferative T cells obtained from mice infected with influenza virus. A proliferative response to A/Port Chalmers/1/73 virus (H3N2) was first detectable in spleen cells 5 days postinfection. Activity persisted in immunized mice for at least 12 months. The duration of immune responsiveness detectable in the 3H-thymidine incorporation assay contrasts with previously reported data indicating a relatively transient appearance of splenic T cell immunity detectable by 51Cr release cytotoxicity assays on influenza-infected target cells. These experiments clearly indicate that splenic T cells from mice infected with influenza virus proliferate in vitro when exposed to antigens of the infecting virus and that they can distinguish between A and B type influenza viruses. The proliferative T cell recognition of influenza viruses within the A type, however, appears to have a broad cross-reactivity, in contrast to the specificity previously shown by cytotoxic T cells. Data obtained from A/Port Chalmers/1/73 virus treated with various anti-influenza sera suggest that the hemagglutinin glycoprotein is of considerable importance in the antigenic recognition by, and stimulation of, influenza-immune proliferative T cells. These assays of the T cell responses to influenza infection should be of value in investigating the complex immune response of the host to influenza viruses.
Enterically Induced Immunologic Tolerance
Authors: Richman Lee K. , Chiller Jacques M. , Brown William R. , Hanson Donald G. , Vaz Nelson M. 
Published: December 2022

Abstract
Specific immune unresponsiveness was induced in inbred mice (BDF1) by the administration of soluble ovalbumin (OVA) by gastric intubation. Anti-hapten (DNP) responses likewise were specifically diminished when animals were fed autologous carrier (OVA or keyhole limpet hemocyanin). Adoptive transfer of spleen cells demonstrated that the tolerant state could be maintained in irradiated recipient mice, and specific anergy could be transferred to normal recipient animals. Adoptive suppression was mediated by T lymphocytes, as demonstrated by nylon wool fractionation and susceptibility of the cells to anti-Thy 1.2 and complement. Transferred B cells had neither suppressive nor augmentative effects. Enteric administration of OVA also specifically diminished antigen-induced DNA synthesis of primed lymph node T cells, although suppressor cells were not identified in the lymph nodes per se.