bluuebunny/crossref_metadata_2025_split huggingface dataset:
The antimetastatic function of concomitant antitumor immunity. I. Host Ly-1+2+ effector T cells prevent the enumeration of metastatic tumor cells in a biological assay.
Authors: Dye S E 
Published: December 2022

Abstract
A mouse survival assay was evaluated for its suitability to enumerate metastatic P815 tumor cells in the draining lymph node and spleen of a B6D2 F1 (H-2b X H-2d) host bearing a primary intradermal P815 tumor. The mouse survival assay is based on the linear relationship between the log10 number of P815 tumor cells (H-2d) injected i.p. into mice and their mean survival time. It was found that the assay is capable of quantifying as few as 10 tumor cells in lymph node and spleen, but only if cell suspensions of these organs are treated with anti-H-2b serum and complement, in order to selectively destroy H-2bd host cells. This was necessary because host cells from the lymph node and spleen of a tumor-bearing host possessed antitumor functions, in that they were capable of destroying the H-2d P815 tumor cells when admixed with the tumor cells and injected i.p. into 800-rad irradiated test recipients. The kinetics of acquisition and loss of host cells with antitumor function and the Ly phenotype of these host cells suggest that they are the same cells that give the tumor-bearing host the capacity to express concomitant immunity against a tumor implant.
IL 2 alone is mitogenic only for Tac-positive lymphocytes in human peripheral blood.
Authors: Taylor D S , Kern J A , Nowell P C 
Published: December 2022

Abstract
To investigate the ability of interleukin 2 (IL 2) alone to induce proliferation of resting human lymphocytes, we stimulated human peripheral blood mononuclear cells (PBMC) with an immunopurified preparation of IL 2 or with phytohemagglutinin (PHA). Proliferation and the percent of cells expressing IL 2 receptors were assessed over 6 days of culture. Regardless of the stimulus, the percent of cells bearing an IL 2 receptor paralleled the amount of proliferation, and proliferation was inhibited by an anti-IL 2 receptor monoclonal antibody (anti-Tac). When stimulated by IL 2 alone, less than 8% of PBMC expressed an IL 2 receptor after 24 hr of culture. Stimulation by IL 2 caused both proliferation and IL 2 receptor expression to increase over the entire culture period (routinely to 75,000 cpm and 50% respectively). When colchicine was added (to inhibit cell division), the percent of cells bearing an IL 2 receptor did not increase. IL 2 alone also induced proliferation of PBMC depleted of accessory cells, with the same kinetics but reduced peak response. Both accessory cells and supernatants that showed IL 1 but not IL 2 activity augmented this proliferation 50 to 100%. In contrast to the effect of IL 2, 25 to 50% of PBMC stimulated by PHA expressed an IL 2 receptor after 24 hr of culture. PHA-induced proliferation and IL 2 receptor expression peaked early in the culture period (routinely to 100,000 cpm and 50% respectively within 3 days), and colchicine did not inhibit the early induction of IL 2 receptors on PBMC. Our findings indicate that unlike PHA, IL 2 induces proliferation of PBMC (or PBMC depleted of accessory cells) by expanding the small percentage of cells in a resting population that already express IL 2 receptors. IL 2 does not appear to induce IL 2 receptors on cells previously lacking this molecule. We also find that IL 1 can enhance the response to IL 2 alone.
Establishment of an interleukin 2-dependent T cell line derived from a patient with severe aplastic anemia, which inhibits in vitro hematopoiesis.
Authors: Herrmann F , Griffin J D , Meuer S G , Meyer zum Büschenfelde K H 
Published: December 2022

Abstract
Circulating mononuclear cells from a patient developing severe aplastic anemia during the course of non-A, non-B hepatitis were found to be virtually entirely composed of in vivo activated suppressor T cells (Ia+T8+). These cells were used to establish a new permanent cell line, termed SMAA, by using phytohemagglutinin, Ebstein-Barr virus-transformed irradiated B cells, allogeneic irradiated peripheral blood mononuclear cells, and recombinant interleukin 2 to investigate the relationship of aplastic anemia-derived circulating T cells to bone marrow failure. SMAA cells, now in continuous culture for more than 9 mo, were shown to inhibit proliferation of purified myeloid progenitors and their differentiation into early and late appearing neutrophil and eosinophil colonies by 90%, whereas monocyte colonies were much less affected. Similarly, growth of erythroid colonies and bursts was almost completely inhibited, as was anti-mu-induced B cell proliferation and lectin-induced T cell proliferation. This inhibition of hematopoiesis was mediated by the release of a soluble factor that was sensitive to acid (pH 2), heat (56 degrees C), and trypsin. Monoclonal and polyclonal antibodies to interferon-gamma could abrogate the inhibitory effects of SMAA supernatant, but more than 10(4) neutralizing U/ml had to be added. The effects of SMAA could be duplicated by adding 10(4) U/ml of purified recombinant interferon-gamma to colony and proliferation assays. The concentration of interferon-gamma in SMAA supernatant was estimated to be greater than 3 X 10(3) National Institutes of Health reference U/ml by immunoradiometric assay. These results demonstrate that some patients with aplastic anemia have circulating T cells that are capable of prolonged in vitro secretion of interferon-gamma causing severe inhibition of in vitro hematopoiesis, and these cells can be expanded into permanent lines for studies on their regulatory properties.
Identification of Ki (Ku, p70/p80) autoantigens and analysis of anti-Ki autoantibody reactivity.
Authors: Francoeur A M , Peebles C L , Gompper P T , Tan E M 
Published: December 2022

Abstract
Anti-Ki (Ku, p70/p80) autoantibodies, named after the prototype patient Kikuta by Tojo et al., occur in approximately 10% of patients with SLE, often in association with anti-Sm autoantibodies. The immunofluorescent staining pattern characteristic of anti-Ki antibodies is diffuse speckled nuclear, although some substrates show nucleolar staining as well. Anti-Ki sera specifically immunoprecipitated two protein antigens, Ki86 (Mr 86,000) and Ki66 (Mr 66,000), from radiolabeled cell extracts. The Ki system was found to be immunologically identical to the Ku system described by Mimori et al. and the p70/p80 system described by Reeves. The Ki primary in vitro translation products were identified and proved similar in size to the cellular antigens. The Ki antigens were purified from human spleen by immunoaffinity chromatography followed by SDS-PAGE. The purified Ki antigens proved to be closely related by amino acid composition, and did not appear to be phosphorylated, glycosylated, or associated with RNA. The Ki antigens were found to bind to DNA, in agreement with the observations on the Ku and p70/p80 antigens. They were found to be widely conserved in mammals and were coordinately expressed in all tissues tested. Anti-Ki autoantibodies were purified by antigen-affinity chromatography and were tested by immunoblotting. The antibodies were classified as class I, II, or III, depending on their reactivity with the Ki antigens in immunoblots. Class I antibodies cross-reacted with both Ki antigens, class II antibodies reacted solely with Ki66, and class III antibodies reacted solely with Ki86. These results suggest that at least three different epitopes are present on the Ki autoantigens and that patients differ in their autoantibody response to each epitope.
Active suppression of host-vs-graft reaction in pregnant mice. VII. Spontaneous abortion of allogeneic CBA/J x DBA/2 fetuses in the uterus of CBA/J mice correlates with deficient non-T suppressor cell activity.
Authors: Clark D A , Chaput A , Tutton D 
Published: December 2022

Abstract
The mammalian fetus has been viewed as an unusually successful type of "allograft" and "unexplained" spontaneous abortion as a possible example of maternal rejection. Previous studies have shown the presence of small lymphocytic suppressor cells in the murine decidua which block the generation and reactivation of anti-paternal cytotoxic T lymphocytes (CTL) and lymphokine-activated killer cells (LAK) by elaborating a factor that inhibits the response to interleukin 2 (IL 2). A deficiency of these suppressor cells was associated with implants of xenogeneic Mus caroli embryos in the Mus musculus uterus which are infiltrated by maternal lymphoid cells and aborted. We have also shown a deficiency of such suppressor cells in the lymph nodes draining the uterus of CBA/J females in the process of aborting their semi-allogeneic CBA X DBA/2 F1 progeny. CBA/J females possess significantly lower levels of decidua-associated non-T suppressor cells on day 8.5 to 10.5 of allopregnancy than do mothers that will produce large litters of live babies. The F1 embryos are infiltrated by maternal lymphocytes prior to abortion, and the infiltration and abortion rate appears to be augmented by pre-immunization with paternal DBA/2 spleen cells. Susceptibility to spontaneous abortion is dependent upon maternal age and strain of male mate, and the high abortion rate of CBA/J mated to DBA/2 males can be reduced by immunization with BALB/c spleen cells. The CBA/J x DBA/2J mating combination provides a model of spontaneous abortion in which immunologic factors play an important role and demonstrates that the association between deficiency of decidua-associated suppressor cells and xenopregnancy failure also holds true for the failure of allopregnancies resulting from natural within-species mating.
Independent regulation of granulocyte-macrophage colony-stimulating factor and multi-lineage colony-stimulating factor production in T lymphocyte clones.
Authors: Kelso A , Metcalf D , Gough N M 
Published: December 2022

Abstract
When murine T lymphocyte clones were cultured with purified recombinant IL 2, a dose-dependent increase in the production of granulocyte-macrophage colony-stimulating factor (GM-CSF) was observed. Whereas these clones produced both GM-CSF and multi-lineage CSF (multi-CSF) when cultured with concanavalin A, IL 2 induced the production of GM-CSF in the virtual absence of detectable multi-CSF. In addition, IL 2 synergistically enhanced the production of both GM-CSF and multi-CSF by some antigen- or Con-A-stimulated clones. Like Con-A-induced CSF production, GM-CSF production in the presence of IL 2 required protein synthesis but could occur in the absence of proliferation by the clone. Analysis of dose-response curves for stimulation of CSF production by Con A in the presence and absence of IL 2 suggested that Con A and IL 2 activated GM-CSF synthesis by different mechanisms. These results indicate that the coordinate production of two factors by a single T cell clone stimulated with Con A can be dissociated when the clone is stimulated with IL 2.
Membrane factors responsible for homologous species restriction of complement-mediated lysis: evidence for a factor other than DAF operating at the stage of C8 and C9.
Authors: Shin M L , Hänsch G , Hu V W , Nicholson-Weller A 
Published: December 2022

Abstract
Species-restricted lysis of complement refers to the relative inefficiency of complement to lyse cells from the homologous species. Restriction occurs at least at the steps involving C3/C5 convertase formation and the C9 insertion phase of the complement cascade, and is presumed to be mediated by inhibitory factors in the target cell membrane. In this study, we have examined whether decay accelerating factor (DAF), a membrane protein known to modulate C3/C5 convertase activities on cell surfaces, acts as a regulatory protein in species-restricted lysis of human erythrocyte (E). The role of DAF was assessed in homologous lysis by the classic pathway, in reactive lysis, and in lytic steps requiring C8 and C9. The results indicated that DAF participated in regulating C3/C5 deposition on the surface of homologous E, but had no effect on homologous restriction in reactive lysis and in the reaction of C8 and C9 with antibody-sensitized E C1-7. Treatment of E with pronase or with dithiothreitol (DTT) abolished the restricting effect of homologous C8/C9, indicating that species-restricted lysis by C5b-9 involves membrane factor(s) sensitive to pronase and DTT.
Molecular characterization of antibodies bearing Id-460. I. The structure of two highly homologous VH genes used to produce idiotype positive immunoglobulins.
Authors: Dzierzak E A , Janeway C A , Richard N , Bothwell A 
Published: December 2022

Abstract
The heavy chain immunoglobulin genes encoding a variety of antibodies specific for DNP or Pasteurella pneumotropica and bearing the dominant idiotype of MOPC 460, Id-460, were cloned and sequenced. The VH genes encoding the M460 and D35 (DNP binding) antibodies were found to be homologous but not identical to the VH gene encoding the LB8 (P. pneumotropica binding) monoclonal antibody. Two of at least eight genes in the VH460 cross-hybridizing gene family can encode Id-460 positive antibodies. The VH460 gene family overlaps with the gene family described by VH36-60 and more completely describes this germ-line VH gene family. We have previously demonstrated a genetic requirement for VK1 expression in order to observe the expression of Id-460 in anti-DNP antibody responses. Southern blot analysis of these monoclonal antibody-producing cells demonstrates, as with the cross-hybridizing VH, that two cross-hybridizing VK1 genes (VK1A and VK1C) can be used to encode Id-460-positive immunoglobulins. We demonstrate that immunoglobulin idiotype determinant expression can be the result of the expression of nonidentical but highly homologous genes in the VH460 cross-hybridizing VH gene family and also in the VK1 cross-hybridizing VL family.
Rabbit major histocompatibility complex. I. Isolation and characterization of three subregions of class II genes.
Authors: Sittisombut N , Knight K L 
Published: December 2022

Abstract
Approximately 300 kb of DNA from the rabbit major histocompatibility complex class II region has been cloned from two genomic libraries. Four alpha chain genes and ten beta chain genes were identified in the recombinant phage and cosmid clones by hybridization with human class II cDNA probes. These genes were classified into three subregions (R-DP, R-DQ, and R-DR) based on hybridization analyses with human DP, DQ, and DR subregion genes under stringent conditions. Two alpha genes and one beta gene were assigned to the R-DP subregion, one alpha gene and one beta gene to the R-DQ subregion, and one alpha gene and eight beta genes to the R-DR subregion. In each subregion, the alpha gene and at least one beta gene were closely linked and were oriented in a manner similar to those in the homologous subregions of human and mouse. A combination of cloning data and genomic blot analyses indicated that the rabbit genome contains a minimum of four alpha-chain genes. The results suggested that there has been evolutionary conservation of the subunit organization of the alpha- and beta-chain genes as well as the coding sequences of these genes and that the mammalian ancestor possessed three distinct MHC class II subregions before diversification of human, mouse, and rabbit.
Desferoxamine blocks IL 2 receptor expression on human T lymphocytes.
Authors: Carotenuto P , Pontesilli O , Cambier J C , Hayward A R 
Published: December 2022

Abstract
Thymidine uptake by PHA-stimulated human lymphocytes is reduced in the presence of 100 microM or greater concentrations of the iron-chelating agent desferoxamine (DF). We assessed expression of IL 2 receptor, 4F2 and Ia antigens, IL 2 production, and cell cycle progression by blood mononuclear cells (MNC) stimulated by PHA in the presence or absence of DF to determine whether the lack of T cell proliferation was a manifestation of inhibition of an earlier activation event. Tac antigen expression on PHA-stimulated MNC was inhibited by DF throughout 8 days of culture, and those cells which were positive had a low density of Tac antigen as compared with controls without DF. Expression of other activation antigens, 4F2 and Ia, was not impaired by DF. The supernatants of the DF-containing and control cultures contained equivalent IL 2 activity, as measured on the HT-2 cell line. Cell cycle analysis of these cultures shows that the addition of DF at the beginning of culture blocks most cells from undergoing G0 to G1 transition, whereas later addition of DF arrests the progression of the T cell blasts through the cell cycle. Separation of cells cultured with PHA and DF into Tac+ and Tac- subsets showed that progression from G0 to G1 was restricted to the former subset. These results suggest that interference with IL 2 receptor expression might contribute to the block in mitogen-induced proliferation caused by DF.
Evidence for direct renal injury as a consequence of glomerular complement activation.
Authors: Boyce N W , Holdsworth S R 
Published: December 2022

Abstract
An isolated perfused kidney (IPK) preparation was used to study the functional consequences of antibody-initiated glomerular complement activation in an environment devoid of circulating inflammatory cells. Control IPK, with antibody bound to the glomerular basement membrane (GBM) (mean +/- SEM, 165.0 +/- 5.7 micrograms globulin/g renal cortex), were perfused with a 5% albumin solution. Control urinary protein excretion was 0.306 +/- 0.112 mg/min, renal vascular resistance (RVR) was 4.72 +/- 0.69 mgHg/ml/min, and the glomerular filtration rate (GFR) was 0.41 +/- 0.01 ml/min/g. To produce glomerular complement activation, IPK with equal quantities of bound antibody (167.0 +/- 6.1 micrograms/g) were perfused with fresh plasma. Glomerular complement activation was associated with linear deposition of C3 on the GBM, a significant increase in protein excretion (3.317 +/- 1.077 mg/min; p less than 0.001) and RVR (10.15 +/- 1.85 mmHg/ml/min; p less than 0.001), and a decline in GFR (0.38 +/- 0.01 ml/min/g; p less than 0.05). Equivalent IPK perfused with decomplemented plasma demonstrated neither glomerular complement deposition nor augmented renal injury. By using both complement repletion and depletion techniques, this study demonstrates that antibody-initiated glomerular complement activation produces direct, neutrophil-independent renal injury. Thus, activated complement components may directly contribute to antibody-induced immune renal injury, in addition to their well established role in the recruitment of circulating inflammatory cells.
Immunotherapy for myasthenia gravis: a murine model.
Authors: Christadoss P , Dauphinee M J 
Published: December 2022

Abstract
In vivo therapy with monoclonal antibody (mAb) GK1.5, which recognizes a glycoprotein antigen designated L3T4 on murine helper T lymphocytes, either prevented or suppressed the development of murine lupus, autoimmune encephalomyelitis, and collagen arthritis. The L3T4 antigen in the mouse is analogous to the human Leu-3/T4 antigen expressed on helper T lymphocytes, because they both participate in the T cell response to class II major histocompatibility complex (MHC) antigens. Class II MHC genes and I-A antigens mediate murine experimental autoimmune myasthenia gravis (EAMG) induced by acetylcholine receptor (AChR) autoimmunity. We studied the efficacy of mAb GK1.5 as an immunotherapeutic agent for murine EAMG. Therapy with mAb GK1.5 not only suppressed established autoimmunity to AChR but also prevented loss of muscle AChR in mice with EAMG. Moreover, permanent remission of clinical muscle weakness was induced if mAb GK1.5 therapy was initiated after the onset of clinical disease. Because the function of the Leu-3/T4 determinant on human helper T lymphocytes is analogous to the murine L3T4 determinant, use of antibody to the Leu-3/T4 determinant as an immunotherapeutic agent may provide a way to control the progression of human MG.
Recognition of a hybrid HLA-DP-associated determinant by a human T lymphocyte clone.
Authors: Eckels D D , Hartzman R J , Johnson A H 
Published: December 2022

Abstract
Alloreactive, human T cell clones were derived from an HLA-DPw1-specific primed lymphocyte typing cell line by limiting dilution. The specificities of the clones were analyzed with allogeneic stimulator cells and in family segregation studies. One clone, TLC 56.94, recognized some, but not all, DPw1-positive stimulator cells and in two families, failed to proliferate in response to stimulatory cells from DPw1-homozygous individuals. The simplest explanation for these results is that TLC 56.94 recognizes a hybrid alloantigen produced by transcomplementation or transassociation between an element of DPw1 and some other gene product.
Induction and regulation by monokines of hepatic synthesis of the mouse serum amyloid P-component (SAP).
Authors: Le P T , Mortensen R F 
Published: December 2022

Abstract
The in vitro synthesis by mouse hepatocytes of the major acute-phase reactant, serum amyloid P-component (SAP), was induced either by inflammatory macrophages or by the addition of monokine(s), including IL 1. A single cell assay for enumerating SAP-secreting hepatocytes was developed. An increase in the frequency of SAP-synthesizing hepatocytes was found during the acute phase of inflammation. Macrophages elicited with a sterile inflammatory agent, when cultured with hepatocytes, both induced new SAP synthesis by the hepatocytes and increased the number of SAP-producing hepatocytes by sevenfold. Inflammatory macrophage culture supernatants induced new SAP synthesis in hepatocytes; however, the inducing activity did not correlate with the IL 1-dependent thymocyte-proliferating activity. Purified IL 1 alone increased SAP production without increasing the number of hepatocytes secreting SAP. A mixture of purified IL 1 with non-IL 1 monokines both increased the number of SAP synthesizing hepatocytes and the amount of SAP secreted per cell. Two non-IL 1 monokines of 70 to 80 Kd and 30 to 40 Kd were responsible for hepatocyte induction. The inducing activity was not neutralized by anti-mouse IL 1 antibody. IL 1 did contribute to the acute phase response by inducing more SAP synthesis per hepatocyte. The findings suggest that both the induction of nonsynthesizing hepatocytes into new SAP synthesis and the enhancement of the amount of SAP produced per hepatocyte are responsible for the increase in blood levels of SAP during the acute phase of inflammation.