bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activation of natural killer-derived cytotoxic T lymphocytes. I. Regulation by macrophage and prostaglandins.
Authors: Ting C C , Hargrove M E 
Published: December 2022

Abstract
The present study describes a mechanism that regulates the activation of cytotoxic T lymphocytes (CTL) derived from natural killer (NK) cells. In the absence of antigenic stimulation, polyclonal activation of cytotoxic lymphocytes was induced by culturing the splenic responders with exogenous peritoneal macrophages and indomethacin. The effectors were characterized as T cells, whereas the precursors were of NK origin. To activate these NK-derived CTL, although there was no need for direct contact between responding precursors and macrophages, the role of macrophages could not be substituted by the addition of exogenous IL 2, macrophage supernatant, or IL 1. In contrast, supernatant from syngeneic lymphocyte-macrophage cultures with indomethacin induced CTL generation. This finding indicates that other lymphokines might also be produced and that they are essential for CTL activation. The need for indomethacin, a prostaglandin (PG) synthetase inhibitor, indicated that PG also played a regulatory role. The addition of 1 X 10(-9) M to 1 X 10(-8) M exogenous PGE2 to the cultures in the first 24 to 48 hr completely suppressed CTL activation. Our results clearly show that through regulation by macrophages and PG, NK-derived precursors differentiated into mature CTL. A different receptor repertoire appeared to be present in different clones of NK precursors. In the absence of antigenic stimulation, removal of the restriction by PG allowed the macrophages or their products to interact with the lymphocyte to produce various lymphokines. These lymphokines further signaled the NK precursors to be polyclonally activated and to differentiate into CTL.
Further characterization of cooperative interactions of monoclonal antibodies.
Authors: Ehrlich P H , Moyle W R , Moustafa Z A 
Published: December 2022

Abstract
We reported previously that mixtures of some monoclonal antibodies directed against the glycoprotein hormone human chorionic gonadotropin (hCG) had a higher affinity for the antigen than either monoclonal antibody separately. The synergistic interaction could no longer be detected when one of the antibodies was replaced with its F(ab) fragment. This cooperative interaction has now been further characterized. One-half of 10 possible pairs prepared from five IgG1 monoclonal antibodies against hCG result in a synergistic interaction. The addition of an IgG2b monoclonal antibody to one of the IgG1 monoclonal antibodies also induces a cooperative interaction, which shows that the effect is not subclass restricted. Cooperative interactions between antibodies are also not restricted to solution conditions; adsorption of one antibody to a solid support appears to increase the cooperative effect. Indeed, one pair of antibodies that failed to bind hCG synergistically in solution did so when one antibody was bound to a solid surface. The liquid phase antibody also has an effect on the specificity of the solid phase antibody. The sensitivity of the solid phase assay system has enabled us to develop a rapid method of determining if two monoclonal antibodies can bind to an antigen simultaneously. A quantitative theoretical model has been devised that successfully predicts the cooperative behavior observed between antibodies and should be useful in devising conditions that result in sensitive solid phase radioimmunoassays.
Trypanosomal surface coat variant antigen causes polyclonal lymphocyte activation.
Authors: Diffley P 
Published: December 2022

Abstract
Variant antigen, the primary component of the surface coat of the salivarian trypanosome, when injected i.v. into mice at dosages encountered during acute infections, produced some of the immunopathogenic phenomena associated with acute African trypanosomiasis. Trypanosome-infected and variant antigen-treated mice had splenomegaly caused by proliferation of null cells, B and T lymphocytes, and macrophages. Splenic B lymphocytes were nonspecifically activated to produce antibodies to sheep erythrocytes (SE), to trinitrophenylated-SE, and to fluoresceinated-SE. This polyclonal activation apparently depleted antigen-reactive lymphocyte populations as indicated by a reduced SE-specific, plaque-forming cell response after immunization in vitro. As judged from the results of in vitro immunization and mitogen assays, injections of variant antigen did not induce nonspecific immunosuppression, which indicated that the polyclonal B cell activation and nonspecific immunosuppression may be uncoupled events induced by different parasite products. The polyclonal lymphocyte activation was induced with variant antigen isolated by either ion exchange or lentil lectin column chromatography and by variant antigen isolated from antigenically dissimilar Trypanosoma brucei rhodesiense and Trypanosoma brucei brucei clones.
Isolation of alloreactive CTL clones with cyclical changes in lytic activity.
Authors: Howe R C , Russell J H 
Published: December 2022

Abstract
We have isolated two H-2Dd specific CTL clones from CBA anti-DBA/2 MLC that undergo changes in lytic activity against tumor and Con A blast target cells as a consequence of weekly stimulation with irradiated allogeneic cells and conditioned medium from secondary MLC. Lytic activity is highest on days 2 to 3 after stimulation, and lowest on days 5 to 7. CTL that had been irradiated on day 0 before stimulation have significantly greater activity on day 2. Conditioned media alone, in the absence of added allogeneic stimulator cells is capable of supporting, in a dose-dependent fashion, the increase in activity. Collectively, these changes are similar to those described for the induction of lytic activity in nonlytic CTL populations from long-term MLC, and suggest that these cloned lines may be useful to study the modulation of lytic activity of CTL in culture.
Studies on the mechanism of the human natural killer cell lethal hit: evidence for transfer of protease-sensitive structures requisite for target cell lysis.
Authors: Hiserodt J C , Britvan L J , Targan S R 
Published: December 2022

Abstract
These studies analyze the effects of various enzymes on the terminal, killer cell-independent (KCIL) stages of the human natural killer (NK) cytolytic mechanism. The addition of trypsin (T), chymotrypsin (CT), or papain (P) to standard NK reaction mixtures (PBL or LGL and K562 cells) completely ablated cytolytic activity, whereas collagenase was ineffective. Inhibition by T was reversed by preincubation with soybean trypsin inhibitor (SBTI) or fetal calf serum, indicating that the inhibition was indeed due to T. Kinetic analysis with the Ca++ pulse experiment indicated that T, CT, and P inhibited lysis well beyond the Ca++-dependent (EDTA-sensitive) stages and essentially stopped further 51Cr release at the time of addition. This observation was confirmed by the ability of T, CT, and P to block lysis during KCIL of programmed K562 targets that were detached from NK cells by EDTA and were suspended in dextran-containing media. The lysis of K562 cells by natural killer cell-derived cytotoxic factors (NKCF) was also blocked by T and CT but not by P. Inhibition of NKCF activity by T could be reversed by SBTI or fetal calf serum. The ability of T, CT, or P to inhibit the lysis of "programmed" K562 targets during KCIL indicates that the NK lethal hit is an active process mediated by protease-sensitive structures, possibly NKCF, delivered to the target cell by the NK cell during the Ca++-dependent programming steps.
Leu-3+ T cells produce gamma-interferon in patients with recurrent herpes labialis.
Authors: Cunningham A L , Merigan T C 
Published: December 2022

Abstract
Interferon-gamma (IFN-gamma) was spontaneously secreted by peripheral blood mononuclear cells cultured from patients soon after recurrent herpes labialis (RHL) or was induced from macrophage-T lymphocyte cultures in vitro with HSV antigen. Circulating Leu-3+/Leu-2- cells produced the spontaneous IFN almost exclusively. In the HSV antigen-stimulated culture system the same subset was the predominant producer of IFN-gamma. The IFN-gamma producing leu-3+ lymphocytes were plastic nonaderent but nylon wool adherent, and may be analagous to the murine Th 2 helper cell. In contrast to one lymphocyte subset being the major IFN-gamma producer in this viral disease, mitogen stimulation induced IFN-gamma from all (Leu-2+/2- and Leu-3+/3-) subsets, with panning as the separation technique. As mitogens circumvent the normal processing and presentation of antigen, the RHL system described above may provide a more accurate picture of the relative contributions of helper (Leu-3+) and cytotoxic/suppressor (Leu-2+) T cells to IFN-gamma production in herpes viral disease.
Subunit structure of guinea pig Ia.1 antigens.
Authors: Quill H , Schwartz B D 
Published: December 2022

Abstract
Since their discovery in 1976, the guinea pig Ia.1 and Ia1,6 antigens were thought to be borne on a single protein species of approximately 26,000 m.w. This report demonstrates that the Ia.1 and Ia.1,6-bearing molecules are typical Ia.1 heterodimeric structures, consisting of acidic alpha-chain and basic beta-chain subunits. The mature Ia.1 and Ia.1,6 alpha-chains have an apparent size of 29,000 m.w., less than the 33,000 m.w. observed for the mature Ia.3,5 alpha-chain. Furthermore, pulse-chase studies and studies with tunicamycin demonstrate that the precursors of the Ia.1,6 alpha- and Ia.3,5 alpha-chains are clearly distinct. On the basis of their association with Ir genes and on their structural features, we conclude that the Ia.1 and Ia.1,6-bearing molecules are similar to other Ia antigens in subunit organization and biochemical properties.
Role of inflammatory cells in Chagas' disease. I. Uptake and mechanism of destruction of intracellular (amastigote) forms of Trypanosoma cruzi by human eosinophils.
Authors: Villalta F , Kierszenbaum F 
Published: December 2022

Abstract
The ability of human eosinophils (EOS) to take up and kill intracellular (amastigote, AMA) forms of Trypanosoma cruzi was investigated as a part of our efforts to define the role of inflammatory cells, typically found in acute chagasic lesions, in clearance and destruction of the parasite. In experiments in which purified EOS and AMA were mixed and allowed to interact for 1 hr, EOS uptake of the parasites was demonstrable by electron microscopy and was confirmed by measurements of incorporation of [3H]AMA. The degree of parasite uptake increased with the AMA to EOS ratio, and was detectable as early as 20 min after the initial contact. After 1 hr, a time when minimal AMA damage was noted, 40% of the EOS were found to contain parasites. Damage inflicted on the AMA was frequently seen 2 hr after removal of free AMA; largely destroyed parasites were a common occurrence after 4 hr. The electron microscopic observations were confirmed by kinetic measurements of the release of 3H-labeled materials by EOS that had ingested radiolabeled AMA. The AMA were systematically found within the EOS vacuoles and were never seen free in the cytoplasm. Fusion of the EOS granules with AMA-containing vacuoles was frequently observed and the presence of EOS granule major basic protein (MBP) in the vacuole content was demonstrated immunocytochemically. MBP was around the AMA and bound to parasite structures, including the subpellicular microtubules. Heparin, a polyanion previously shown to abrogate MBP-mediated destruction of blood forms of T. cruzi, inhibited intracellular killing of AMA by EOS. Two other polyanions, chondroitin sulfate and dextran sulfate, had similar effects. In an EOS-free system, the presence of MBP resulted in AMA lysis; this reaction was inhibited by anti-MBP antibody. Taken together, these results favor the notion that EOS contribute to the elimination of T. cruzi AMA from infected tissues through phagocytosis, leading to an intravacuolar lytic process in which at least MBP plays a role.
Mechanism of cell-mediated cytotoxicity at the single cell level. VIII. Kinetics of lysis of target cells bound by more than one cytotoxic T lymphocyte.
Authors: Perelson A S , Macken C A , Grimm E A , Roos L S , Bonavida B 
Published: December 2022

Abstract
We measured the effects of having multiple cytotoxic T lymphocytes (CTL) bound to one target cell by using the single-cell cytotoxicity in agarose assay. We found that even though there is variability in the time at which individual target cells are lysed, we can identify a general trend: the mean rate of lysis increases with the number of CTL bound per target cell, reaching a maximum when the CTL-target cell ratio is three. Combining a quantitative model for the rate of lethal hitting in multicellular conjugates with a multi-event model for the rate of target cell disintegration, we developed a new multistage kinetic model for predicting the rate of target cell lysis in multiple lymphocyte-target cell conjugates. The variability in the time at which target cells are hit and the variability in the time until they disintegrate are incorporated into the model. By analyzing our measured data in the context of the multistage kinetic model, we were able to estimate via nonlinear least squares regression the target cell disintegration rate, but not the lethal hitting rate. Lethal hitting appeared to be too fast, when compared with disintegration, to significantly affect the time of target cell lysis. By using previously determined values of the lethal hitting rate for single lymphocyte-target cell conjugates and by postulating that lymphocytes act independently of each other in delivering lethal hits, we were able to estimate the rate at which target cells are hit in multiple-lymphocyte single target cell conjugates. By using this estimate of the lethal hitting rate and the regression estimate of the disintegration rate, the multistage kinetic model gave a quantitative fit to our data. From this analysis, we found that the rate at which a target cell disintegrates after being lethally hit increases with the number of CTL per conjugate. This result is quite surprising, because once the first hit has been received, a target cell can disintegrate in a killer cell-independent manner. Under the conditions of our experiment, it appears as if target cell disintegration is not killer cell-independent. Furthermore, our analysis of the time course of target cell disintegration suggests that the process is not governed by simple first order kinetics, but rather by a more complex multistep mechanism.
Polymorphism of C lambda genes and units of duplication in the genus Mus.
Authors: Scott C L , Potter M 
Published: December 2022

Abstract
The number of Ig C lambda genes in nine geographically widespread species from the four subgenera in the genus Mus was estimated from the number of Bam HI and Eco RI restriction fragments that hybridize under high stringency conditions to cDNA probes of BALB/c inbred mouse origin (Mus musculus domesticus). Three closely related species in the subgenus Mus, M. musculus, M. spretus, and M. spicelegus, show considerable variation in the number of C lambda genes. Estimates of gene numbers in these animals range from two C lambda genes in M. spretus from Puerto Real, Spain to 12 C lambda genes in M. musculus musculus from Studenec, Czechoslovakia. Strains of mice carrying either six or 10 C lambda genes were derived from a single population of M. musculus domesticus from Centreville, MD. The hybridization patterns of mice exhibiting C lambda gene amplification indicate that duplications are of relatively recent origin and probably occurred by reiteration of a DNA segment closely related to the 6.5 kb [C lambda 3 - C lambda 1] unit found in BALB/c inbred mice. Three more distantly related species in the subgenus Mus, and a species representing the Nannomys subgenus all appear to carry only four C lambda genes. DNA of species representing the Coelomys and Pyromys subgenera hybridized weakly to the C lambda cDNA probes, but these animals also have no more than four C lambda genes. Thus, there may be a base number of four C lambda genes in most species in the genus Mus. All inbred strains of mice so far examined also have only four C lambda genes, but no feral M. musculus examined have fewer than six C lambda genes. One explanation of the discrepancy in the number of genes between inbred and feral M. musculus is that C lambda genes were deleted during the process of inbreeding.
Characterization of recirculating lymphocytes in rheumatoid arthritis patients: selective deficiency of natural killer cells in thoracic duct lymph.
Authors: Fox R I , Fong S , Tsoukas C , Vaughan J H 
Published: December 2022

Abstract
Five patients with rheumatoid arthritis (RA), who were treated by lymphocyte depletion by using thoracic duct drainage (TDD), provided an opportunity to characterize the phenotype and function of their recirculating lymphocytes. We found that: a) thoracic duct lymphocytes (TDL) were similar in their proportion of T cells (83% +/- 6 OKT3+), OKT4+ subset (65% +/- 8), and OKT8+ subset (22% +/- 6) to peripheral blood lymphocytes (PBL): b) fewer natural killer-like cells were present in TDL (5% +/- 4 Leu-7+; 2% +/- 2 Leu-11+: 8% +/- 2 OKM -1+) than in PBL (20% +/- 10 Leu-7+: 11% +/- 6 Leu-11+; 18% +/- 5 OKM -1) (p less than 0.01); c) TDL differed from synovial fluid lymphocytes ( SFL ) and synovial membrane lymphocytes ( SML ) in that TDL lacked a high percentage of activated lymphocytes (T cells bearing Ia antigen, OKT10 , and transferrin receptor): d) immature T cells (expressing either OKT6 antigen or reactive with peanut agglutinin) were not found in TDL even late in the course of TDD: and e) in vitro functional studies demonstrated that TDL were similar to PBL in their ability to synthesize immunoglobulin after mitogen stimulation and to generate cytotoxic T lymphocytes capable of lysing autologous EBV-transformed B cells. However, natural killer activity, as measured by lysis of K562 cells was significantly lower in TDL than PBL (p less than 0.05). These results demonstrate that natural killer cells defined by phenotype and function are excluded from thoracic duct lymph and thus have a circulation pattern different from most T cells.
Release of leukotrienes by human monocytes on stimulation of their phagocytic receptor for particulate activators.
Authors: Williams J D , Czop J K , Austen K F 
Published: December 2022

Abstract
The respective capacities of adherent human monocytes to metabolize endogenous arachidonic acid into leukotrienes C4 (LTC4) and B4 (LTB4) in response to activation with an ionophore, A23187, or to phagocytosis of unopsonized zymosan particles and IgG-sensitized sheep erythrocytes ( EsIgG ) were compared under optimal conditions for each stimulus. Resolution of the cellfree supernatant, after ionophore activation, by reverse-phase high performance liquid chromatography (RP-HPLC) identified only two products which eluted at the retention times of LTC4 and LTB4. There was correspondence between their quantitation by integrated optical density and radioimmunoassay, and the recoveries from the initial supernatant were 80% by radioimmunoassay. Activation of adherent monocytes from 12 donors by ionophore and by zymosan particles released 68.1 ng and 10.0 ng LTB4 and 29.5 ng and 2.1 ng LTC4, respectively. With trypsin pretreatment, the monocytes responded fully to ionophore activation but were inhibited in their response to zymosan particles as assessed by phagocytosis and leukotriene release, indicating that the zymosan stimulus acted through a trypsin-sensitive membrane receptor. When the response of adherent monocytes from nine donors to zymosan particles and to EsIgG were compared at identical particle concentrations and with similar numbers of ingesting monocytes, zymosan elicited LTB4 release (mean 6.7 ng) from all and LTC4 (mean 1.5 ng) from eight donors, while EsIgG caused low level release of LTB4 (mean 0.7 ng) from six and LTC4 from only one of the donors. Neither zymosan nor ionophore stimulation led to the metabolism of exogenously added [3H]LTB4 or [3H]LTC4 as assessed by RP-HPLC of the cellfree supernatants and by quantitation of the eluted labeled products. Thus, transmembrane activation of adherent monocytes by their receptor for particulate activators, in contrast to stimulation of their IgG-Fc receptor, reproducibly releases substantial quantities of LTB4 and LTC4, and may represent an important mechanism for regulating the microenvironment in the nonimmune host.
A monoclonal antibody with reactivity restricted to normal and neoplastic plasma cells.
Authors: Anderson K C , Bates M P , Slaughenhoupt B , Schlossman S F , Nadler L M 
Published: December 2022

Abstract
A monoclonal antibody that defines a new and distinct plasma cell antigen, termed PC-1, was developed against human plasmacytoma cells. This antigen is strongly expressed on normal plasma cells isolated from bone marrow and on abnormal plasma cells isolated from myelomas, plasma cell leukemias, and plasmacytomas. The antigen is not detected on normal T or B lymphocytes, granulocytes, or monocytes, and with the exception of plasma cells, is absent on malignancies of B, T, or myeloid origin. Utilizing pokeweed mitogen to induce human B lymphocyte differentiation in vitro, PC-1 is expressed when B cell determinants are lost and the plasmacytoid morphology, intracytoplasmic immunoglobulin-staining, and surface PCA-1- and T10-staining characteristic of plasma cells appear. This antigen is useful for the study of the terminal stages of normal B cell differentiation to plasma cells, and may offer insight into the heterogeneity of the plasma cell dyscrasias.
Macrophage activation to kill Leishmania tropica: characterization of a T cell-derived factor that suppresses lymphokine-induced intracellular destruction of amastigotes.
Authors: Nacy C A 
Published: December 2022

Abstract
Factors obtained from phorbol myristate acetate (PMA)-stimulated EL-4 thymoma cells, a continuous T cell line, suppressed lymphokine-induced macrophage activation to kill intracellular Leishmania tropica amastigotes. Suppression of this macrophage effector activity was dependent upon concentration of EL-4 fluids admixed with lymphokines in infected macrophage cultures, and was not due to residual PMA or factors released from unstimulated EL-4 cells. Fluids from PMA-stimulated EL-4 cells did not affect the expression of microbicidal activity by macrophages activated in vivo as a consequence of infections with Mycobacterium bovis strain BCG, nor did they abrogate intracellular killing activities by C3H/HeJ macrophages primed by BCG infection and triggered by lymphokines in vitro. That the action of this EL-4 suppressor activity was at the priming stage of macrophage activation was confirmed by kinetic studies: EL-4 fluids added to lymphokine-treated cells in the first 4 hr of treatment completely suppressed intracellular killing of L. tropica; fluids added after 4 hr were not effective. The effects of these EL-4 factors appeared to be selective: of three effector activities of activated macrophages tested, induction of resistance to infection, tumor cytotoxicity, and intracellular destruction of L. tropica, only intracellular killing by lymphokine-treated macrophages was significantly suppressed. These T cell-derived soluble suppressor factor(s) may provide insight into mechanisms of immunosuppression during leishmanial disease and perhaps other intracellular parasitic infections.