bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of nonspecific killer cells by interleukin 2-containing supernatants.
Authors: Teh H S , Yu M 
Published: December 2022

Abstract
In the absence of specific antigen stimulation, nonspecific killer cells were induced by culturing C57BL/6 lymph node or spleen cells with interleukin 2-containing supernatants. These supernatants were obtained from stimulation of either rat spleen cells with concanavalin A or a variant of the T cell lymphoma, EL4 (H-2b) with phorbol myristic acetate. The ability of the EL4 supernatant to induce nonspecific killer cells was abrogated by absorption with an interleukin 2-dependent T cell line or by concanavalin A-stimulated spleen cell blasts, but not by lipopolysaccharide-stimulated spleen cell blasts or by a non-interleukin 2-producing EL4 line. Partially purified interleukin 2 from EL4 supernatants could also support nonspecific killer cell induction. The induction of cytolytic cells by interleukin 2 is sensitive to gamma-irradiation and has a D omicron of 120 rad. The nonspecific killer cells induced are likely cytotoxic T lymphocytes; the majority of the precursor and effector cells bear the Thy-1 alloantigen marker. These nonspecific killer cells killed a broad spectrum of target cells, including concanavalin A- and lipopolysaccharide-induced splenic blasts of syngeneic or allogeneic mice, a syngeneic tumor, and a cloned allogeneic cytotoxic T cell line. The frequency of precursors for nonspecific killer cells in C57BL/6 lymph node and spleen cells are 1/7000 and 1/12,000, respectively. Clonal analyses revealed that these nonspecific killers exhibit heterogeneity with respect to their target cell specificities. The induction of nonspecific killers by interleukin 2-containing supernatants is partially dependent on nylon wool-adherent cells; in antigen-stimulated cultures the most specific killer cells were obtained from cultures in which nylon wool-nonadherent lymph node responder cells were stimulated with nylon wool-nonadherent allogeneic splenic stimulator cells that were treated with anti-Thy-1 antibody and complement. The relevance of these findings with respect to the frequencies and fine specificities of cytotoxic T lymphocytes generated in interleukin 2-supplemented cultures is discussed.
Role of interferon in human natural killer activity against target cells infected with HSV-1.
Authors: Bishop G A , Glorioso J C , Schwartz S A 
Published: December 2022

Abstract
Human natural killer (NK) cells show high cytotoxic activity against target cells infected with herpes simplex virus type 1 (HSV-1). Substantial amounts of interferon (IFN) were generated in co-cultures of NK effector cells and infected target cells; however, the cytotoxic activity seen against a specific infected cell target did not correlate with the amount of IFN induced. The production of IFN increased steadily from 4 to 18 hr of co-culture, as did NK activity; however, IFN production peaked 4 hr later than NK activity. Pretreatment of NK effector cells with exogenous IFN increased cytotoxic activity against all targets tested, but the differential pattern of reactivity against cells infected with wild type and mutant viruses was unaltered. When effector cells were treated with the RNA synthesis inhibitor actinomycin D before co-culture with virus-infected targets, IFN production was markedly reduced, without a concomitant reduction in cytotoxicity. Similarly, the addition of anti-IFN antiserum to co-cultures greatly decreased the available IFN present, but had no effect on NK activity. We conclude that the induction of cytotoxic activity in co-cultures of NK effector cells and HSV-1-infected target cells is independent of the induction of IFN.
Functional characteristics of histamine receptor-bearing mononuclear cells. I. Selective production of lymphocyte chemoattractant lymphokines with histamine used as a ligand.
Authors: Center D M , Cruikshank W W , Berman J S , Beer D J 
Published: December 2022

Abstract
Mitogens and antigens have been the traditional ligands for activating lymphocytes in vitro for the elaboration of lymphokines. Recently, histamine, by interaction with histamine-type 2 receptors on T lymphocytes, has been found to induce the production of one lymphokine, histamine-induced suppressor factor (HSF), that inhibits lymphocyte proliferation and lymphokine production in vitro. Because the biologic effects of HSF appear to be confined to alterations in lymphocyte function, we assessed the ability of soluble products of histamine-stimulated human blood mononuclear cells to affect another lymphocyte function, motility. Utilizing a modified Boyden chamber assay to assess lymphocyte migration, we identified chemoattractant activity for human blood and rat splenic T lymphocytes in histamine-induced mononuclear cell supernatants. No neutrophil or monocyte chemoattractant activity was present. Sephadex G-100 gel filtration of histamine-induced supernatants showed the lymphotactic activity eluted with a 56,000 m.w. This activity was cationic as determined by its elution pattern from a Sephadex QAE anion exchange matrix with a single pl of 9.0 to 9.4 determined by isoelectric focusing in sucrose. Its biologic activity is predominantly chemokinetic in nature, is stable to heating at 56 degrees C for 30 min, but is sensitive to the effects of trypsin and neuraminidase. These physicochemical and functional characteristics establish it as identical to a recently described concanavalin A-induced (Con A) lymphotactic lymphokine (LCF). Mononuclear cells that did not adhere to a histamine affinity matrix were unable to produce LCF when subsequently stimulated with histamine or Con A. Mononuclear cells incubated with histamine and diphenhydramine produced LCF; the addition of cimetidine eliminated LCF production. In fact, supernatants from cells incubated with histamine and cimetidine significantly inhibited lymphocyte migration, a phenomenon explainable by the two regions of lymphocyte migration inhibitory activity that were present in the Sephadex G-100 chromatography of crude histamine-induced supernatants. These data suggest that a subset of lymphocytes defined by the presence of histamine-type 2 receptors is capable of producing LCF while cells that bear histamine-type 1 receptors produce lymphocyte migration inhibitory activity.
Human granulocyte surface molecules identified by murine monoclonal antibodies.
Authors: Skubitz K M , Pessano S , Bottero L , Ferrero D , Rovera G , August J T 
Published: December 2022

Abstract
We have investigated the nature of the antigens recognized by four classes of mouse anti-human monoclonal antibodies that characteristically reacted with neutrophilic granulocytes and their precursor cells, but not with monocytes or other normal hemopoietic cells. The antigenic targets of the majority (9/12) of the independently isolated monoclonal antibodies were present on two surface glycoproteins (Mr 145,000 and 105,000) and glycolipids. This antigen(s) was also detected on granulocyte precursor cells, including the bone marrow granulocyte/monocyte progenitor cells (CFU-GM). The same antigen(s) detected by these monoclonal antibodies was also present in non-hemopoietic cell lines (colon carcinoma and neuroblastoma). Three other antigens, defined by monoclonal antibodies AHN-8, L12.2, and L13.1 and present on granulocytes and their mid-late precursor cells, could not be identified as proteins but were detected in a protein-free glycolipid extract of these cells. The diversity of the antigens was confirmed by cross-competition experiments and by the identification of their different patterns of reactivity with cell lines and bone marrow cells.
Ligand-induced association of rat lymphocyte membrane proteins with the detergent-insoluble lymphocyte cytoskeletal matrix.
Authors: Woda B A , McFadden M L 
Published: December 2022

Abstract
There are two classes of membrane protein capping on the basis of ligand requirements. Surface immunoglobulin (Slg), the prototype of the first class, requires a single ligand for cap induction. RT1 (rat histocompatibility proteins) requires two antibodies for cap induction. The lateral mobility of Slg is relatively restricted compared with RT1. These differences may be due to differential interaction with the cytoskeleton. After ligand binding 71% of Slg becomes detergent insoluble and is associated with the lymphocyte cytoskeletal matrix. The insolubilization occurs at 4 degrees C and is not inhibited by sodium azide or cytoskeleton-active drugs. The insolubilized ligand-receptor complex can be solubilized by a cytoskeleton destabilizing buffer. In contrast, only 20% of RT1 becomes associated with the lymphocytic cytoskeleton after ligand binding. The ligand-induced receptor-cytoskeleton interaction influences capping behavior and may play a role in cell activation.
Sequential induction of phospholipid methylation and serine esterase activation in a B cell differentiation factor (BCDF)-stimulated human B cell line.
Authors: Kishi H , Miki Y , Kikutani H , Yamamura Y , Kishimoto T 
Published: December 2022

Abstract
The incubation of CESS cells with BCDF induced phospholipid methylation, i.e., 3H-methyl incorporation into phosphatidylcholine and phosphatidyl-N-monomethyl-ethanolamine, within 15 to 30 min. A threefold increase of 3H-DFP-binding was also observed in BCDF-stimulated CESS cells 2 hr after stimulation, showing the activation of serine esterase after phospholipid methylation. The inhibitors of methyltransferase, SIBA, adenosine, or HEH showed a dose-dependent inhibitory effect not only on phospholipid methylation but also on serine esterase activation and on BCDF-induced IgG production; DFP inhibited IgG production but not phospholipid methylation. The treatment of cells with DFP in the presence of SIBA abrogated the irreversible inhibitory effect of DFP on IgG production. These results showed that BCDF stimulation induced phospholipid methylation that set the stage for serine esterase activation and IgG induction.
Characterization of alloimmunization-induced T lymphocytes reactive against AKR leukemia in vitro and correlation with graft-vs-leukemia activity in vivo.
Authors: Truitt R L , Shih C Y , Lefever A V , Tempelis L D , Andreani M , Bortin M M 
Published: December 2022

Abstract
We have reported that immunization of H-2k mice with lymphoid cells from various allogeneic strains induced a population of cells that could eliminate first-passage spontaneous AKR leukemia from the spleens of immuno-suppressed AKR (H-2k) hosts. In the present study, we examined the nature of the cells responsible for this graft-vs-leukemia (GVL) reaction and compared them to cytolytic cells detected in vitro. Spleen cells from alloimmunized CBA/J (H-2k) mice were selectively depleted of various subpopulations by treatment with antibody and complement (C), then tested in vivo for GVL reactivity. Cell suspensions depleted of Thy-1.2+, Lyt-1+, or Lyt-2+ lymphocytes had no significant GVL reactivity, whereas suspensions depleted of NK-1.2+ cells retained GVL reactivity. The GVL-reactive cells persisted in H-2-compatible donor mice for up to 56 days. Lyt-1+2+ lymphocytes that were cytotoxic for cultured AKR leukemia cells in vitro could be detected in the spleens of alloimmunized H-2-compatible mice after expansion of the cells in T cell growth factor. Using quantitative limiting dilution cytotoxicity assays, we found that the frequency of leukemia-reactive cytotoxic lymphocytes (CL) in the spleen showed a direct correlation with the GVL efficacy of the cells in vivo. Alloimmunization was essential for induction of the GVL-reactive cell population. CL in alloimmunized mice consisted of heterogeneous cytotoxic specificities; i.e., some CL were leukemia-specific, others lysed only nonleukemic AKR target cells, and a third group mediated killing of both leukemic and nonleukemic target cells. The CL appeared to be H-2 restricted and specific for non-H-2 antigens shared by the AKR leukemia and the alloimmunizing cells.
Antigen-induced lymphomagenesis: identification of a murine B cell lymphoma with known antigen specificity.
Authors: Arnold L W , LoCascio N J , Lutz P M , Pennell C A , Klapper D , Haughton G 
Published: December 2022

Abstract
CH12, a murine B cell lymphoma derived in B10 H-2aH-4bp/Wts mice after transfer of SRBC hyperimmunized spleen cells into an adult-thymectomized, sublethally irradiated, syngeneic recipient, is demonstrated to bear surface IgM specific for a determinant found on SRBC and ChRBC. The Ig specificity has been demonstrated by rosetting assays and complement-dependent hemolysis. The removal of CH12 surface IgM by capping with anti-mu or with anti-CH12 idiotype, but not with anti-gamma or with irrelevant anti-idiotype, eliminated the formation of rosettes between CH12 and SRBC or ChRBC. The absorption of CH12 Ig produced in vitro, with either SRBC or ChRBC but not with HRBC, removed all hemolysin activity against SRBC, demonstrating that only one CH12 product was responsible for the reactivity with both SRBC and ChRBC. CH12 has a surface phenotype of a relatively mature B cell expressing surface Ig (IgM-mu,kappa) and la antigens, but lacking Thy-1 or detectable Fc or C3 receptors. CH12 also expresses the antigen Lyt-1. Growth of CH12 in vivo or in vitro results in the generation of up to 3% direct PFC and serum hemolysin, which shows that CH12 is not irretrievably "frozen". The generation of PFC and serum hemolysin is associated with increased population density, and the rate of PFC and serum hemolysin accumulation cannot be explained by simple cell division. A continuously secreting hybridoma derived from CH12 was used to purify the CH12 IgM to facilitate studies of protein sequence and idiotype.
Anti-mu induces lymphoma in germfree congenitally athymic (nude) but not in heterozygous (nu/+) mice.
Authors: Gershwin M E , Ohsugi Y , Castles J J , Ikeda R M , Ruebner B 
Published: December 2022

Abstract
To further our understanding of the role of host immunity in the development of lymphoid neoplasia, groups of germfree BALB/c nude and nu/+ mice were either followed unmanipulated or were treated, beginning at birth, with anti-mu, normal goat IgG or with lipopolysaccharide (LPS). The survival and development of neoplasia of all groups of animals were monitored up to 2 yr. Nude mice, under germfree and specific pathogen-free (spf) conditions, had a higher incidence of lymphoid neoplasia and reduced survival when compared to nu/+ littermates. The incidence of lymphoid tumors in nude mice under spf or germfree conditions was 7.2 and 8.7%, respectively, in comparison to 0% in nu/+ animals. Treatment of germfree nude mice with anti-mu, but not with goat IgG, increased the incidence of lymphoid tumors to 39%. Anti-mu did not significantly change the incidence of lymphoid neoplasia in nu/+ animals. Treatment of nu/nu and nu/+ mice with LPS, however, led to a several-fold increase in the appearance of neoplasia, to values of 25.4% in nude and 10% in nu/+ mice. Lymphoid neoplasia found in either unmanipulated, anti-mu, or IgG-treated germfree or spf mice included Thy-1.2+, surface IgM+, and IgG+ tumors. In contrast, all the lymphomas found in LPS-treated mice were surface IgM+. Thus, whereas LPS may have generated a relatively homogeneous group of tumors, anti-mu may have randomly increased the normal incidence of spontaneous tumors. Moreover, although there was significant variation in the histologic appearance of tumors, both within treatment groups as well as in different areas of the same animal, only LPS-treated mice were regularly noted to have distant nonlymphoid involvement, with lesions found in liver, lung, and kidney. In contrast, the incidence of nonlymphoid neoplasia was similar and was less than 2.5% in all groups.
Tumor-associated macrophages of mouse mammary tumors. II. Differential distribution of macrophages from metastatic and nonmetastatic tumors.
Authors: Mahoney K H , Fulton A M , Heppner G H 
Published: December 2022

Abstract
Macrophage subpopulations were isolated by counterflow centrifugal elutriation from a number of closely related mammary tumors originally derived from a single spontaneous tumor in a BALB/cfC3H mouse. Each tumor line had its own distinct characteristics with regard to tumor cell distribution, macrophage size (density), macrophage content, and macrophage distribution. Although there is no correlation with the metastatic potential of the tumors for the first three characteristics listed, distinct differences are apparent between metastatic and nonmetastatic tumors in macrophage distribution into the elutriated fractions. The distribution of the tumor-associated macrophages was shifted toward the later fractions in the metastatic tumors (lines 66 and 410.4), with approximately 40% more macrophages in fractions 3 and 4 than in those fractions from the nonmetastatic tumors (lines 67 and 168). The levels of three ectoenzymes, leucine aminopeptidase (LAP), alkaline phosphodiesterase I (APD), and 5' nucleotidase (5'N) were determined for macrophages from the elutriated fractions as well as for the total tumor digest. No significant differences were observed in absolute levels of either LAP or APD between most of the fractions from the different tumor lines. Differences were seen between the fractions in levels of 5'N among the lines and in ADP levels between lines 66 and 168 from the total tumor digest. Striking differences in ectoenzyme levels were apparent when the activity was normalized to macrophage surface area: macrophages from line 66 tumors were 3- to 17-fold higher in their LAP concentrations than were macrophages from either 67 or 168 tumors. Each tumor line had a unique and reproducible pattern of macrophage-associated prostaglandin E (PGE) synthesis. The three nonmetastatic tumor lines showed peak PGE levels in fraction three with lower levels in fraction 2, whereas the highly metastatic tumor yielded more active macrophages in fraction 2 vs fraction 3. Changes in PGE levels were associated with differing ectoenzyme levels. Macrophages in fraction 3 from metastatic tumors were enriched for populations with high LAP activity and low PGE levels. Conversely, macrophages from nonmetastatic tumors exhibited lower LAP activity in fraction 3 vs 2 and increasing PGE levels. Thus, differences between metastatic and nonmetastatic mammary tumors were seen in 1) distribution of macrophages in the elutriation fractions, 2) size of infiltrating macrophages, 3) macrophage ectoenzyme concentrations, and 4) macrophage-associated PGE levels.
Prevention of lethal, minor-determinate graft-host disease in mice by the in vivo administration of anti-asialo GM1.
Authors: Charley M R , Mikhael A , Bennett M , Gilliam J N , Sontheimer R D 
Published: December 2022

Abstract
Graft-vs-Host disease (GVHD) remains a devastating problem in human bone marrow transplantation (1, 2). Because removal of Thy-bearing cells from the donor inoculum has prevented GVHD in murine models (3, 4), it has been hoped that a similar cell surface antigen or combination of antigens could be found in humans. Unfortunately, treatment of human donor cells with various T cell antisera has not yet been successful in preventing GVHD (5). Encouraging results have been reported in five patients who received bone marrow depleted of T cells by the sequential use of soybean agglutinin and the differential sedimentation of cells forming rosettes with sheep red blood cells (6). Although donor T cells are thought to be necessary for initiating GVHD, the immunopathogenesis of GVHD is still not understood. Because donors and recipients are routinely major histocompatibility complex matched and chosen to be nonreactive in mixed lymphocyte cultures human GVHD is thought to result from minor histocompatibility antigen disparities. Lopez and coworkers (7, 8) found a strong association between the incidence of human GVHD and the pretransplant levels of natural killer (NK) activity of the recipients; when the recipient NK activity was low, GVHD rarely developed. They speculated that the NK cell lineage is serving as an important stimulator-inducer. We therefore examined the in vivo effects of anti-asialo GM1 on a murine model of GVHD based on minor antigen disparity. This antiserum has several immunologic effects, including a profound NK suppression. We found that the mice treated with this antibody have normal survival rates, even though they do develop histologic GVHD in the skin. This finding suggests the possibility of a new prophylactic approach to human GVHD and raises many questions regarding the function of asialo GM1-bearing cells in immune regulation.
Role of Ly-1:Qa1- and Ly-1:Qa1+ inducer T cells in activation of Ly-23 effectors of suppression of antibody production in mice.
Authors: Eardley D D , Hu S K , Gershon R K 
Published: December 2022

Abstract
Ly-2+ effectors of T cell-mediated suppression require inducing signals from antigen and a helper cell bearing the Ly-1+:Qa1+ surface phenotype. In this report, we have further examined the helper cell requirements for suppressor cell induction of antibody production in mice. By using the T cell subset education procedure in vitro, we have activated T cells to sheep red blood cells (SRBC) antigens and then purified Ly-2 cells before testing for suppressor activity in assay cultures of defined T and B cell subsets. We have confirmed our previous observations that Ly-1+:Qa1+ cells are required for activation of T suppressors, but have found that under the appropriate conditions, there is not a strict requirement for the Ly-123 subset of T cells. Furthermore, if Ly-23 cells are stimulated in the presence of Ly-1+:Qa1- T cells, effective suppressors can be obtained only if a source of Ly-1:Qa1+ inducers is added to the assay culture. If Ly-23 cells are activated by antigen in the absence of Ly-1 cells, subsequent exposure to the Ly-1+:Qa1+ subset under the conditions tested here is not sufficient to activate suppressors. These results show that effectors of suppression, like B cells and cytotoxic T lymphocytes, may respond to two helper cells.
Clonal analysis of T cell unresponsiveness to alloantigens induced by neonatal injection of F1 spleen cells into parental mice.
Authors: Feng H M , Glasebrook A L , Engers H D , Louis J A 
Published: December 2022

Abstract
Alloantigen-specific T cell precursors present in spleen cell populations obtained from parental mice that were rendered tolerant by the neonatal injection of F1 spleen cells were quantitated by clonal analysis, i.e., limiting dilution techniques. The results demonstrate that the frequencies for cytolytic as well as TCGF-producing (helper) and MAF-producing T cell precursors were dramatically reduced in tolerant spleen cell populations. The unresponsive state was antigen specific and could not be transferred in vitro in cell mixing experiments. Therefore, clonal deletion (or inactivation) would appear to represent a major mechanism for the observed tolerant state in this model system.