bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proteolytic cleavage of Ii to p25.
Authors: Thomas L J , Nguyen Q V , Elliott W L , Humphreys R E 
Published: December 2022

Abstract
The 25,000-Da protein that is seen in immunoprecipitates with antibodies to class II MHC molecules or to Ii was shown to be a C-terminal fragment of Ii. [35S]Methionine pulse-chase labeling of polyclonally activated B lymphocytes or lymphoblastoid cell lines demonstrated maximal appearance of p25 in Percoll-separated endosomal fractions at 20- to 40-min chase times (studies in progress). This finding was consistent with the view that proteolysis of Ii to p25 and its release might catalyze the binding of digested foreign peptides to class II molecules and/or govern release of such charged complexes to traffic to the cell surface. We examined the structural relationship of p25 to Ii and the basis for cleavage of a relatively restricted site just external to the transmembranal segment. [35S]Methionine-labeled Ii and associated molecules were immunoprecipitated with a mAb to native Ii and then denatured, resolubilized, and subjected to a second immunoprecipitation with various antibodies. Two antisera to C-terminal peptides of Ii (183 to 193 and 192 to 211), but not antibodies to an N-terminal peptide (12 to 28), did immunoprecipitate p25. The three antibodies to C-terminal and N-terminal peptides all immunoprecipitated denatured Ii proteins. The mAb to Ii immunoprecipitated [35S]methionine-labeled p25 but not [35S]cysteine-labeled p25. This finding was consistent with loss of a portion of Ii containing the only cysteine in Ii, Cys28. Digestion of class II MHC Ag-Ii complexes with various proteases yielded proteins migrating at and near p25 in two-dimensional electrophoretic gels. Upon increasing the duration of protease digestion, the 25,000-Da fragments were relatively resistant to further digestion. This observation was consistent with the presence of secondary structures (domains) leaving a relatively protease-sensitive (Ig hinge-like) region in Ii near its insertion into the membrane.
Generation of lipid neutrophil chemoattractant by irradiated bovine aortic endothelial cells.
Authors: Matzner Y , Cohn M , Hyam E , Razin E , Fuks Z , Buchanan M R , Haas T A , Vlodavsky I , Eldor A 
Published: December 2022

Abstract
Radiation injury to blood vessels is associated with an acute inflammatory process. We investigated the capacity of cultured bovine aortic endothelial cells (BAEC) to produce chemotactic factors after radiation injury. BAEC in serum-free media were irradiated with a cobalt-60 Gammacell 220 and the cell supernatants were assayed for chemotactic activity for human neutrophils in a Boyden chamber. There was a rapid release of chemotactic activity into the BAEC supernatants which was dependent both on the dose of radiation (5 to 40 Gy) and the time between irradiation and sample collection. In contrast, isolation of BAEC lysates by freeze-thawing was not associated with the presence of similar chemotactic activity. The chemotactic activity released from the irradiated BAEC was not destroyed by boiling nor by treatment with trypsin. The release of the chemotactic activity was, however, inhibited by the addition of a lipoxygenase inhibitor but not by the addition of a cyclooxygenase inhibitor before the irradiation. The chemotactic activity was recovered from the cell supernatants in the lipid phase after extraction with chloroform/methanol. Furthermore, the chloroform/methanol extracts co-eluted with authentic leukotriene B4 when the BAEC were prelabeled with [14C] arachidonic acid. However, we were unable to detect endogenous leukotriene B4 with RIA. Instead, the only detectable endogenous lipid present in the supernatants was 13-hydroxyoctadecadienoic acid which is derived from linoleic acid via the lipoxygenase pathway. 13-Hydroxyoctadecadienoic acid, however, had no chemotactic activity. These findings suggest that endothelial cells rapidly release a chemotactic agent after irradiation, the release of which is associated with a lipoxygenase pathway. The release of this chemotactic activity may account in part for the acute inflammatory response that is observed after ionizing irradiation.
Trypanosoma cruzi-induced suppression of IL-2 production. II. Evidence for a role for suppressor cells.
Authors: Tarleton R L 
Published: December 2022

Abstract
Suppression of IL-2 production during experimental Chagas' disease accounts at least in part for the overall depressed state of the immune system in infected mice. The failure to produce IL-2 in response to mitogen stimulation is not the result of the lack of cells capable of producing IL-2, but appears to be due to regulation of IL-2 production by suppressor cells. This conclusion is supported by cell-mixing experiments where the ability of cells from infected mice to suppress normal spleen cell IL-2 production is evident. Although depletion of plastic and Sephadex G-10 adherent cells results in modest increases in IL-2 production by spleen cells from infected mice, even in the presence of normal adherent cells as a source of IL-1 producers, IL-2 production does not approach normal levels. Also, isolated macrophages are not by themselves suppressive for normal spleen cell IL-2 production, whereas plastic and G-10 nonadherent cells from infected mice are. Depletion of Thy-1+ and Ly-2+ cells not only completely abrogates the ability of spleen cells from infected mice to suppress normal IL-2 production, but results in a cell preparation which actually enhances IL-2 production. Anti-Ly-2 and C treatment of infected spleen cells also markedly enhances their ability to produce IL-2. These results indicate a major role for Ts cells in the regulation of IL-2 production, and a relatively minor role of macrophages as direct effector cells of suppression in this response. The ability to enhance IL-2 production in this system with PG synthesis inhibitors suggests a role for PG-producing cells such as macrophages in the suppressor mechanism, perhaps as inducers of the suppressor effector cells.
Amnion membrane epithelial cells express class I HLA and contain class I HLA mRNA.
Authors: Hunt J S , Andrews G K , Fishback J L , Feess M , Wood G W 
Published: December 2022

Abstract
Amnion epithelial cells in membranes from term deliveries, which have been reported not to express histocompatibility Ag, were evaluated for HLA by using an avidin-biotin immunoperoxidase staining system and for class I HLA mRNA by Northern blotting and in situ hybridization. There were three major findings from these studies. 1) Amnion cells frequently expressed class I HLA. Three mAb to monomorphic determinants of class I HLA were used: 61D2, PA2.6, and W6/32. 61D2 identified 1 of 8 fresh amnion membranes as class I positive whereas PA2.6 identified 4/8 and W6/32 identified 5/8. 2) Amnion cells contained class I HLA mRNA. RNA extracted from amnion membranes hybridized to a class I HLA probe (pHLA1.1) in Northern blotting. In situ hybridization procedures with pHLA1.1 showed that essentially all amnion cells contained class I HLA mRNA. 3) Levels of class I HLA mRNA in amnion cells could be modulated. Exposure of amnion explants to medium containing IFN-gamma enhanced levels of class I HLA mRNA in amnion cells, whereas epidermal growth factor diminished those levels. The results suggest that amnion cells transcribe class I HLA genes and are capable of synthesizing class I H chains but that expression may be modulated by extrinsic regulatory molecules.
Stable T3- and T3+ subclones derived from the mosaic human T cell leukemia cell line, CEM.
Authors: Uppenkamp M , Pittaluga S , Coupland R , Colamonici O , Cossman J 
Published: December 2022

Abstract
An unexplained feature of the human T lymphoblastic leukemia cell line, CEM, is a heterogeneous expression of surface membrane T3-TCR complex. CEM cells constitutively maintain two distinct populations whereby a minority of cells (5 to 16%) express T3 but the remainder do not. From the parental cell line, we have derived stable subclones in which all cells express surface T3 and companion subclones that lack surface T3. Inasmuch as surface T3 expression is contingent on assembly and coexpression of the multichain T3 protein complex with the TCR, we compared the surface T3+ and T3- subclones for their rearrangement and expression of genes of the T3-TCR complex. Restricted DNA of both subclone types showed the identical monoclonal pattern of TCR gene rearrangement seen in the mosaic parental CEM line. Northern blot analysis revealed mRNA transcripts of TCR beta subunit and T3 delta in both the surface T3+ and T3- subclones. However, surface T3+ subclones transcribed abundant full length (1.5-kb) TCR alpha mRNA in contrast to the surface T3- subclones in which TCR alpha transcripts were undetectable. Lack of TCR alpha gene transcription was not attributable to either unrearranged or aberrantly rearranged TCR alpha genes because exposure of surface T3- cells to phorbol ester induced a rapid (15-min) and progressive accumulation of full length (1.5-kb) TCR alpha mRNA. This was followed by surface membrane T3 expression in 24 to 72 h. We conclude that the unusual phenotypic mosaicism of CEM cells is attributable to a reversible lack of transcription of the TCR alpha gene.
Differential responses of B cells from the spleen and lymph node to TNP-Ficoll.
Authors: Goud S N , Muthusamy N , Subbarao B 
Published: December 2022

Abstract
Subcutaneous immunization with the thymus independent Ag, TNP-Ficoll, does not elicit plaque-forming cell response from the regional lymph node B cells even though a good response is obtained with the splenic B cells. Lymph node cells respond well to the thymus independent 1 Ag, TNP-Brucella abortus. Because TNP-Ficoll is a soluble Ag and may not be retained well in the lymph nodes, we emulsified it with Freund's adjuvant and injected it into foot pads. This did not result in any antibody response in the popliteal and inguinal lymph nodes though once again splenic B cells gave excellent responses. We find that the in vivo response to TNP-Ficoll can be induced in the lymph node if TNP-Ficoll is injected along with B. abortus in the foot pads of normal mice. This observation could not be repeated in the splenectomized mice implicating the role of the migration of APC or B cells from spleen to lymph nodes. Similar differential responses are obtained from lymph node and splenic B cells in the in vitro cultures. Lymph node cells respond to TNP-Ficoll with the addition of normal irradiated spleen cells but not with Sephadex G-10-passed spleen cells. This shows the absence of APC or lymphokines which stimulate B lymphocytes to respond to TNP-Ficoll in the lymph nodes. We found that IL-1 but not IL-2 or IL-4 was able to induce TNP-Ficoll response from the lymph node B cells.
Sensitization and desensitization to lethal effects of tumor necrosis factor and IL-1.
Authors: Wallach D , Holtmann H , Engelmann H , Nophar Y 
Published: December 2022

Abstract
BALB/c mice were sensitized to lethal effects of human rTNF-alpha and of human rIL-1 alpha by simultaneous treatment with sublethal doses of actinomycin D (Act D) or D-galactosamine (GalN). In contrast, treatment with sublethal doses of TNF or IL-1 themselves resulted in desensitization of the mice to the lethal effect of these cytokines: mice injected with TNF or IL-1 in the absence of Act D or GalN responded to a second injection of TNF or IL-1, this time together with Act D or GalN, by a significantly delayed death, or even survived. Desensitization developed rapidly (0.5-1.0 h) and abated 24 to 48 h postinjection. Each of the two cytokines induced hyporesponsiveness to its own lethal effect as well as to that of the other. Injection of TNF or IL-1 at sublethal doses resulted also in hyporesponsiveness to the lethal effect of LPS on mice primed with bacillus Calmette-Guérin, an effect which most likely is mediated by TNF and IL-1 produced in those mice in response to the LPS. TNF and IL-1 in combination had an additive effect both in lethality and in desensitization of the mice. These findings suggest that some of the deleterious effects of TNF and IL-1 are modulated by antagonistic mechanisms; mechanisms which can be suppressed by sensitizing agents, specifically by agents inhibiting the synthesis of RNA or protein; but which, in the absence of such agents, are found to be augmented in response to TNF and IL-1, thus resulting in desensitization.
Induction of IL-1 secretion from human monocytes by Fc region subfragments of human IgG1.
Authors: Morgan E L , Hobbs M V , Noonan D J , Weigle W O 
Published: December 2022

Abstract
Peripheral blood-derived human monocytes and the murine P388D1-monocytes-like cell line are induced to secrete IL-1 when stimulated with Fc region but not F(ab) region subfragments obtained from the cleavage of human IgG1 with papain or pepsin. The portion of the Fc region of IgG1 responsible for stimulation of IL-1 secretion appears to be located within the C gamma 3 domain of the molecule. This hypothesis is supported by the observation that the biologically active pepsin-derived pFc' subfragment is located within the C gamma 3 domain and the long-term papain digests containing predominately Fc' are also active. In contrast, short term papain digests containing mostly intact Fc fragments were found to be unable to induce IL-1 secretion.
Angiotensin II (AII)-related idiotypic network. II. Heterogeneity and fine specificity of AII internal images analyzed with monoclonal antibodies.
Authors: Budisavljevic M , Geniteau-Legendre M , Baudouin B , Pontillon F , Verroust P J , Ronco P M 
Published: December 2022

Abstract
Although the structural basis of internal images borne by beta type monoclonal anti-idiotypic antibody (Ab2) begins to be elucidated, there is little information on the repertoire of epitopes which make up the internal images expressed by polyclonal Ab2. We addressed this question by using a two-way approach in the angiotensin II (AII)-related idiotypic network, a system characterized by common occurrence of internal images on rabbit Ab2. First, two sets of internal images were purified in parallel by affinity chromatography on Sepharose 4B covalently linked to either mAb 110 (S4B-110), a mAb specific for a phenylalanine requiring carboxy terminus epitope (Phe8) on AII, or mAb 133 (S4B-133), reactive with a more central epitope also expressed on Phe8 substituted peptide analogs. The respective eluates, EL1 110 and E11 133, exhibited only partially overlapping reactivity, as demonstrated by 1) a different pattern of inhibition by various AII peptide analogues of EL1 110 and E11 133 binding to the same anti-AII antibody (Ab1) (either the homologous polyclonal Ab1 102 or mAb 133), 2) and a distinct profile of EL1 110 and EL1 133 binding to 12 biotinylated monoclonal Ab1 identifying a variety of epitopes on AII. To analyze further the respective distribution of mAb 110 and mAb 133 defined epitopes on Ab2-beta molecules, Ab2 were submitted to sequential affinity chromatography on S4B-110 followed by S4B-133, and the fractionated internal images were characterized by the pattern of binding to the various monoclonal Ab1. It was thus possible to purify two Ab2-beta subpopulations that exclusively imaged the determinant identified by mAb 110 (ii 110) or that identified by mAb 133 (ii 133). A third subpopulation which was successively retained on S4B-110 and S4B-133 expressed both internal images (ii 110 + 133), and was additionally reactive with all the other monoclonal Ab1 tested. In any case, monoclonal Ab1 binding to the different sets of internal images was totally inhibited by an excess of AII. These results indicate that the repertoire of internal epitopes is similar to that of the nominal Ag, but is scattered over distinct subpopulations of Ab2-beta molecules that can be fractionated by affinity chromatography. Some of the latter seem to bear several epitopes and resemble the whole nominal Ag, whereas others appear to image only one determinant. Second, we raised 7 anti-anti-idiotypic mAb (monoclonal Ab3) against affinity-purified Ab2-beta and analyzed their fine specificity for AII.(ABSTRACT TRUNCATED AT 400 WORDS)
Effects of vitamin D3 and IFN-gamma on the synthesis of the second complement component, C2, by a human myeloid leukemia (HL-60) cell line.
Authors: Littman B H , Sanders K M 
Published: December 2022

Abstract
HL-60 cells, a human promyelocytic cell line, can be induced to differentiate along either monocytic or granulocytic pathways. The production of the second complement component, C2, is a marker of monocytic differentiation and can be up-regulated by cytokine stimulation. We studied the effects of IFN-gamma and vitamin D3, two factors previously shown to induce monocytic differentiation of HL-60 cells, on C2 production and C2 mRNA content. We found that HL-60 cells produce little if any C2 but can be induced to synthesize C2 by IFN-gamma. Vitamin D3 pretreatment followed by IFN-gamma stimulation resulted in earlier and greater production of C2. HL-60 cells did not contain detectable amounts of C2 mRNA unless they were stimulated with IFN-gamma. Pretreatment with vitamin D3 followed by IFN-gamma stimulation resulted in a 147% increase in C2 mRNA content compared with IFN-gamma stimulation alone. These results indicate that the up-regulation of C2 production by IFN-gamma and vitamin D3 is pretranslational although additional posttranslational effects were not excluded. C2 production by these cells is a useful marker of monocytic differentiation.
Dissociation between increased surface expression of gp165/95 and homotypic neutrophil aggregation.
Authors: Buyon J P , Abramson S B , Philips M R , Slade S G , Ross G D , Weissmann G , Winchester R J 
Published: December 2022

Abstract
Whether homotypic neutrophil aggregation depends on the quantitative increase of gp165/95 molecules (Mac 1, CR3) recruited to the cell surface during activation was studied using mAb of the CD11b group that recognize distinct epitopes encoded by the alpha-subunit of this glycoprotein. After the addition of antibody MN41, neutrophils did not aggregate in response to a chemoattractant, FMLP. Blockade of preexisting surface gp165/95 by mAb MN41, followed by removal of the excess antibody from the mixture, was used to show that the molecules of gp165/95 newly expressed in response to stimulation by a chemoattractant were incapable of effectively mediating the induced cell-cell interactions of aggregation. Flow cytometry studies confirmed that binding of unlabeled antibody MN41 did not block further increases in surface expression of gp165/95 after stimulation with FMLP. These data suggest that molecules of gp165/95 exhibit two functionally distinct forms, one, present on the surface of freshly isolated neutrophils, that becomes competent to mediate the aggregation response upon activation by a stimulus and a second form that can be translocated to the cell surface by the stimulus but is greatly diminished if not lacking in the ability to participate in that aggregation event.
Cloned Listeria monocytogenes specific non-MHC-restricted Lyt-2+ T cells with cytolytic and protective activity.
Authors: Kaufmann S H , Rodewald H R , Hug E , De Libero G 
Published: December 2022

Abstract
Mice were infected with Listeria monocytogenes and Lyt-2+ T cell clones capable of lysing Ag-primed bone marrow macrophages were established. In accordance with earlier findings obtained at the population level, some T cell clones were identified which lysed bone marrow macrophages of different MHC type provided the relevant Ag was present. This unusual target cell recognition was further analyzed using a T3+, L3T4-, Lyt-2+, F23+, KJ16+ T cell clone, designated L-28. Target cell lysis by this clone was Ag specific, apparently non-MHC restricted. In contrast, YAC cells and P815 cells were not lysed by clone L-28. However, lysis of irrelevant targets could be induced by anti-T3, F23, or KJ16 mAb. Furthermore, Ag-specific lysis was blocked by anti-Lyt-2 mAb and by F(ab)2 fragments of F23 mAb. In addition to its cytolytic activity, clone L-28 produced IFN-gamma after co-stimulation with accessory cells, Ag, and rIL-2 and conferred significant protection on recipient mice when given together with rIL-2. These data suggest that non-MHC-restricted Lyt-2+ killer cells generated during listeriosis are cytolytic T lymphocytes that interact with their target Ag via the T cell receptor/T3 complex and the Lyt-2 molecule and, furthermore, that these cells play a role in anti-listerial resistance. The possible relevance of IFN-gamma secretion and target cell lysis for antibacterial protection is discussed.
Resistance of primary CD8+ cytotoxic T lymphocytes to lysis by cytotoxic granules from cloned T cell lines.
Authors: Nagler-Anderson C , Verret C R , Firmenich A A , Berne M , Eisen H N 
Published: December 2022

Abstract
Recent evidence has shown that cloned, murine CTL cell lines are resistant to the cytotoxic components of the toxic granules they release upon specific interaction with their target cells. Inasmuch as the resistance might be due to selection in culture over many months by repeated exposure to these cytolytic components (which are released repeatedly as a result of the cultured CTL being periodically stimulated by target cells), we asked whether primary CTL are also resistant. The primary CTL were elicited in vivo by i.p. injection of allogeneic tumor cells or in vitro by 5- to 6-day MLC or by 48-h exposure to the lectin Con A. The responding cells were separated into purified CD8+ (i.e., CD4-, CD8+) and purified CD4+ (i.e., CD4+, CD8-) T cell populations that were analyzed for cytolytic activity and for resistance to lysis by toxic secretory granules derived from cloned CTL cell lines. The CD8+ T cells were highly cytolytic and relatively resistant; they retained their cytolytic activity and were lysed to a minimal extent (0 to 10%) by quantities of isolated granules that lysed 80 to 90% of the P815 tumor cell line (tested as a representative standard cell line). The CD4+ T cells, in contrast, had only minimal cytolytic activity and were far more susceptible to granule-mediated lysis. Although the resistance of primary CD8+ T cells is impressive, it is not as pronounced as the resistance of the cloned CTL cell lines, indicating that during long-term culture there is some selection for increased resistance to granule-mediated lysis. In contrast to T cells (especially CD8+ T cells), Ia+ macrophages, isolated from primary immune peritoneal exudates, were highly susceptible to granule-mediated lysis.
Regulation of antibody production by helper T cell clones in experimental autoimmune myasthenia gravis.
Authors: Fujii Y , Lindstrom J 
Published: December 2022

Abstract
Ten acetylcholine receptor (AChR)-specific T cell clones from Lewis rats were studied. These clones had various AChR subunit and peptide specificities, and proliferated in response to antigen on appropriate APC. All the T cell clones were CD4+CD8- and OX22-, helped anti-AChR antibody production by AChR-primed lymph node B cells, and could secrete IL-2. However, several lines of evidence suggested that IL-2 was not the lymphokine that mediated T cell help. B cells primed with native AChR and then exposed in culture to very low concentrations of native AChR effectively presented the Ag to the T cell lines, presumably due to uptake via Ag receptors, but primed B cells were no more effective than were non-specific APC at presenting a synthetic AChR peptide which is recognized by AChR-specific T cells but not by AChR-specific B cells. Increasing AChR doses produced an antibody production response that was bell shaped and low doses stimulated, whereas higher AChR concentrations suppressed the antibody production response. Evidence suggested that AChR exerted its inhibitory effect through the T cells, but not via IL-2.