bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective production of autoantibodies in graft-vs-host-induced and spontaneous murine lupus. Predominant reactivity with histone regions accessible in chromatin.
Authors: Portanova J P , Arndt R E , Kotzin B L 
Published: December 2022

Abstract
The injection of (C57BL/6 X DBA/2)F1 mice with parental DBA/2 lymphoid cells leads to a lupus-like disease in which IgG autoantibodies are targeted to certain nuclear and cell surface antigens. To investigate further the extent of antibody diversity in this graft-vs-host (GVH) model, we studied the specificity of antihistone antibodies induced by the GVH reaction. High levels of IgG antibodies to histones H1 and H2B were detected whereas responses to H2A, H3, and H4 were only marginally elevated above pre-GVH levels. Immunoblotting analysis further revealed that the response to H2B was focused on epitopes that most likely reside in the N-terminal region. In contrast, F1 mice immunized with H2B/RNA complexes in adjuvant produced antibodies to the N terminus as well as to other regions of the H2B molecule. Thus, the antihistone response stimulated by the GVH reaction is only a fraction of the potentially activatable B cell repertoire. We also determined whether antibodies that arise spontaneously in genetically predisposed lupus strains were restricted in their histone reactivity. The response to core histones was highly variable among individual animals of the NZB/NZW and MRL-lpr/lpr strains despite their inbred nature. However, nearly all mice exhibited a preferential reactivity for epitopes in histone regions that are lost after partial trypsin digestion of chromatin. These data demonstrating autoantibody responses that are limited to particular histone regions support a mechanism by which B cells are selectively activated in murine lupus. The predominant production of antibodies to histone regions that are exposed in nucleosomes raises the possibility that chromatin is an antigenic stimulus for histone-specific B cells in this disease.
Spontaneous interferon production by pulmonary leukocytes is associated with lentivirus-induced lymphoid interstitial pneumonia.
Authors: Lairmore M D , Butera S T , Callahan G N , DeMartini J C 
Published: December 2022

Abstract
Ovine lentiviruses share genome sequence, structural features, and replicative mechanisms with HIV, the etiologic agent of AIDS. A lamb model of lentivirus-induced lymphoid interstitial pneumonia, comparable to lymphoid interstitial pneumonia associated with pediatric AIDS, was used to investigate production of leukocyte-soluble mediators. Lentivirus-infected lambs and adult sheep with severe lymphoid interstitial pneumonia had significantly elevated levels of spontaneous interferon (IFN) production from pulmonary leukocytes compared with ovine lentiviruses-infected animals with mild or no lesions of lymphoid interstitial pneumonia or non-infected controls. However, peripheral blood mononuclear cells from lentivirus-infected lambs did not spontaneously release significant amounts of IFN. IFN production by pulmonary lymph node lymphocytes was enhanced in the presence of lentivirus-infected alveolar macrophages. Animals with lentivirus-induced disease and spontaneous IFN production had enhanced virus replication within tissues. The ovine lentiviruses-induced IFN had a m.w. of between 25,000 and 35,000 and was resistant to freeze/thawing procedures. The IFN activity was sensitive to trypsin and stable to low pH and heat. IFN with similar physical and biochemical properties was produced when ovine lentiviruses was added to control leukocyte cultures. IL-2 and PGE2 production and responses to mitogen by pulmonary lymph node lymphocytes of lentivirus-diseased lambs were not statistically different from control animals. Increased local production of IFN in lentivirus-infected host tissues may serve to accelerate the entry of leukocytes into virus-induced lesions promoting cell-mediated tissue damage and also provide increased numbers of cells for virus replication.
T4 endocytosis and phosphorylation induced by phorbol esters but not by mitogen or HIV infection.
Authors: Hoxie J A , Rackowski J L , Haggarty B S , Gaulton G N 
Published: December 2022

Abstract
The T4 (CD4) molecule has been shown to facilitate the interactions of T cells with HLA class II determinants, to function as a signal transducing molecule, and to serve as a receptor for HIV. Recent studies demonstrated that both phorbol esters and antigen stimulation induced the rapid and transient modulation and phosphorylation of T4 on an IL-2-dependent line of cloned peripheral blood T4+ cells. In the current study, we define the kinetics of T4 phosphorylation and internalization induced by phorbol esters and determine the extent to which this metabolic pathway is required for T cell proliferation, activation, and HIV infection. On both peripheral blood T4+ cells and the T cell line Sup-T1, the modulation and internalization of surface T4 induced by phorbol 12, 13-dibutyrate (PDB) was preceded by rapid and transient phosphorylation. On both cell types, by 48 h, T4 was reexpressed on the cell surface in a nonphosphorylated form and was shown to be resistant to phosphorylation and internalization when these cells were reexposed to PDB. In contrast, T4 on the surface of PBL was neither phosphorylated nor down-modulated when PBL were stimulated by PHA, indicating that these effects were not simply the result of T cell activation or proliferation. In additional studies, we demonstrate that this pathway for T4 phosphorylation and internalization is not required for HIV infection by showing that 1) the binding of the HIV gp 120 envelope to T4 does not induce phosphorylation of T4, 2) Sup-T1 cells that are rendered resistant to phorbol ester-induced T4 internalization and phosphorylation by prolonged culture in PDB remain highly susceptible to HIV infection, and 3) clones of HIV-producing cells expressing high levels of surface T4 that is complexed with viral envelope remain susceptible to PDB-induced modulation of T4. This observation suggests that, at least on lymphoid cells, HIV penetration does not occur exclusively by R-mediated endocytosis.
Pre-B cell generation potentiated by soluble factors from a bone marrow stromal cell line.
Authors: Landreth K S , Dorshkind K 
Published: December 2022

Abstract
Two bone marrow stromal cell lines isolated from the adherent layer of a Dexter-type long term bone marrow culture differ markedly in their hemopoietic support capacity. S17 supports myelopoiesis and the differentiation of early B cell precursors into B lymphocytes while S10 supports myeloid cell differentiation and not B lymphopoiesis. The identification of a stromal cell line with B cell support capacity prompted an investigation of whether the effects of S17 were mediated via soluble factors. Results presented herein indicate that medium conditioned by S17 but not S10 contains an activity that can induce the expression of the 220,000 m.w. 14.8 antigen and cytoplasmic mu H chain of Ig in B lymphocyte progenitors that have not yet expressed these markers. Bone marrow cells were depleted of 14.8+, cytoplasmic mu+ pre-B cells on antibody-coated petri dishes. After 24-h liquid culture newly generated pre-B cells were enumerated as cells that expressed cytoplasmic mu H chain of Ig but not Ig L chains by immunofluorescence. Expression of Ly5(220) was monitored by 14.8 antibody binding. This pre-B cell differentiation activity was abrogated by digestion with pronase, aminopeptidase, or carboxypeptidase. Isoelectric focusing data revealed the activity to have isoelectric point of 5.9 to 6.2. S17-conditioned medium was fractionated using HPLC and each fraction tested for pre-B cell-generating activity. Fractions collected from a Superose 12 gel filtration column were found to have two peaks of activity associated with molecules of apparent m.w. of approximately 60,000 and 10,000. Virtually identical peaks of activity were observed when medium conditioned by heterogeneous stromal cell cultures was fractionated. Separation of S10-conditioned medium revealed no cryptic activity. S17-conditioned medium was further characterized by anion exchange chromatography and the majority of the pre-B cell generating activity shown to be associated with the void volume that eluted from a MonoQ column. These fractions were rechromatographed on Superose and the activity again found to be associated with two fractions corresponding to apparent m.w. of 60,000 and 10,000. The S17 pre-B cell differentiation activity appears to result from the presence of a novel molecule because other well characterized mediators had no activity in this short-term liquid culture system. No pre-B cell-generating activity was observed when IL-1 or conditioned medium containing IL-2, IL-3, or IL-4 (B cell stimulatory factor 1) were added to cultures.(ABSTRACT TRUNCATED AT 400 WORDS)
Sodium fluoride reveals multiple pathways for regulation of surface expression of the C3b/C4b receptor (CR1) on human polymorphonuclear leukocytes.
Authors: Okada K , Brown E J 
Published: December 2022

Abstract
We have examined the effects of NaF on C3b receptor (CR1) expression and function in human polymorphonuclear leukocytes (PMN). Plasma membrane expression of CR1 was determined with a monoclonal antibody (3D9); CR1 function was assessed with erythrocytes bearing C3b (EC3b) or C3b oligomers prepared with avidin and biotin. NaF inhibited in a dose-dependent manner CR1-mediated phagocytosis and NaF inhibited f-met-leu-phe or phorbol dibutyrate-induced increases in CR1 expression, with 50% inhibition at 5 mM NaF. Increased plasma membrane expression of CR3 induced by f-met-leu-phe also was inhibited by NaF. However, increased CR1 and CR3 expression due to incubation at 37 degrees C were unaffected by 10 mM NaF. Incubation of PMN with 10 mM NaF depleted 80% of intracellular adenosine triphosphate (ATP) after 10 min. However, inhibition of CR1 function was unrelated to ATP level, inasmuch as normal increases in CR1 expression and in phagocytosis occurred 20 min after removal of NaF, whereas ATP levels remained below 25% of normal. Strikingly, internalization of soluble oligomeric C3b ligands was unaffected by 10 mM NaF, which completely inhibited phorbol dibutyrate-induced CR1 internalization and EC3b phagocytosis. We conclude that there are two different mechanisms for increasing plasma membrane expression of CR1, one of which is inhibitable by NaF. Moreover, there are two distinct pathways of CR1 internalization which can also be distinguished by their sensitivity to NaF.
Polymorphism of the HLA-D region in American blacks. A DR3 haplotype generated by recombination.
Authors: Hurley C K , Gregersen P , Steiner N , Bell J , Hartzman R , Nepom G , Silver J , Johnson A H 
Published: December 2022

Abstract
The polymorphism of HLA class II molecules in man is particularly evident when comparisons between population groups are made. This study describes a DR3 haplotype commonly present in the American black population. Unlike the Northern European population in which almost all DR3 individuals are DQw2, approximately 50% of DR3-positive American blacks express a serologically undefined DQ allelic product. DNA restriction fragment analysis with the use of several unrelated individuals and an informative family has allowed us to identify unique DQ alpha- and beta-fragments associated with the DR3, DQw- haplotype. Based on fragment size, the DQ alpha genes of the DR3, DQw- and DRw8, DQw- haplotypes are similar as are the DQ beta genes of DR3, DQw-; DRw8, DQw-; and DR4, DQw- haplotypes. In addition, a DX beta gene polymorphism has been identified which is associated with some DR3 haplotypes including the American black DR3, DQw- haplotype. cDNA sequence analysis has revealed a DQw2-like alpha gene and a DQ beta gene which is similar to that previously described for a DR4, DQw- haplotype. It is postulated that recombination between DQ alpha and DQ beta genes and between the DQ and DX subregions has generated the various DR3 haplotypes and has played an important role in creating diversity in the HLA-D region.
Molecular mechanisms involved in T cell activation. III. The role of extracellular calcium in antigen-induced lymphokine production and interleukin 2-induced proliferation of cloned cytotoxic T lymphocytes.
Authors: Harris D T , Kozumbo W J , Testa J E , Cerutti P A , Cerottini J C 
Published: December 2022

Abstract
The role that extracellular calcium plays in activating resting cloned cytotoxic T lymphocytes (CTL) to proliferate and to produce lymphokines was examined. In these cells, stimulation with interleukin 2 (IL-2) induced a proliferative response without a concomitant production of macrophage-activating factor (MAF), whereas stimulation with antigen or lectin (in the absence of IL-2) induced MAF production but not proliferation. In the case of IL-2-induced proliferation, extracellular calcium was required to initiate proliferation as well as to prevent cellular arrest later in the G2 + M phase of the cell cycle. In MAF production extracellular calcium was required both to activate the phosphatidylinositol signal-transducing mechanism and to mobilize intracellular calcium in antigen- or lectin-stimulated cytotoxic T lymphocytes. Further, extracellular calcium was required for only 8 of the 18 hr of stimulation time which was needed to achieve maximal MAF production, indicating that both calcium-dependent and -independent events exist in the signal pathway. Additional experiments with calcium ionophores and activators of protein kinase C indicated that although both intracellular calcium mobilization and de novo protein phosphorylation are involved in MAF production, an optimal increase in the level of intracellular calcium by itself is insufficient to induce the production of this lymphokine.
Human monoclonal antibody directed against gag gene products of the human immunodeficiency virus.
Authors: Evans L A , Homsy J M , Morrow W J , Gaston I , Sooy C D , Levy J A 
Published: December 2022

Abstract
Tonsillar B lymphocytes from an asymptomatic individual infected with HIV were transformed with EBV. A cloned lymphoblastoid cell line was obtained that secreted human mAb (IgG4 subtype) against the known gag gene products of 55,000 and 25,000 Da and a protein of 40,000 Da. The latter p40 protein appears to be a HIV gag-related gene product that is also recognized immunologically by individuals infected by HIV. Although the mAb detects infection of cells by different HIV isolates, it does not neutralize HIV or show activity in an antibody-dependent cytotoxicity assay.
Syngeneic monoclonal anti-idiotype antibodies that bear the internal image of a human cytomegalovirus neutralization epitope.
Authors: Keay S , Rasmussen L , Merigan T C 
Published: December 2022

Abstract
Two glycoproteins have been identified on human CMV that induce neutralizing antibody; an 86,000-Da glycoprotein and a 130,000-, 92,000-, and 50,000-Da glycoprotein coimmunoprecipitating complex that appears to be the gB homologue of HSV. We have produced syngeneic monoclonal anti-Id antibodies (mAb2) of the IgM isotype to a CMV-neutralizing monoclonal antibody (mAb1) that is known to bind to the 86,000-Da glycoprotein on the virion envelope. These mAb2 bear the internal image of the original viral antigen as shown by their ability to 1) recognize an interspecies idiotype in CMV-positive human antisera, 2) block mAb1 binding to CMV antigen, and 3) block CMV neutralization by mAb1 in vitro. Immunization of mice with both of these affinity chromatography-purified mAb2 stimulated the production of anti-anti-Id monoclonal antibodies (which we termed mAb3), which bound to the mAb2 by ELISA and neutralized CMV infectivity.
Reactivation of class II antigen expression in murine macrophage hybrids.
Authors: Zuckerman S H , Schreiber R D , Marder P 
Published: December 2022

Abstract
The induction of class II antigen on primary macrophages and on several macrophage cell lines has been demonstrated after exposure to IFN-gamma. The murine macrophage cell line PU5 (H-2d haplotype) does not express class II antigen constitutively and only trace levels are detected after induction with IFN-gamma. In an attempt to understand the nature of the defect in PU5, stable macrophage hybrids were derived by fusing a thymidine kinase-negative variant of PU5 with thioglycollate elicited peritoneal macrophages from CBA/J mice (H-2k haplotype). Hybrid clones isolated after HAT selection had approximately 35% more DNA than the PU5 parent suggesting that chromosomal loss had occurred post-fusion. While none of the hybrids expressed class II antigens of the k haplotype, constitutive expression of class II antigens of the d haplotype was detected by both micro-ELISA and by flow cytometry. Incubation of these hybrids with IFN-gamma resulted in a further increase in class II expression. Co-ordinate reactivation of both I-A and I-E antigens was observed in the PU5-macrophage hybrids. In contrast, although the IFN-gamma receptor on PU5 and the macrophage hybrids was indistinguishable by Scatchard analysis, neither intracellular class II antigen nor transcription of class II mRNA was detected in IFN-gamma-treated PU5. Reactivation was dependent on the PU5 fusion partner and was not related to a general post-fusion event as hybrids formed between PU5 and the murine fibroblast line A9 did not express class II antigen constitutively or after IFN-gamma induction.
The E beta hot spot of recombination in wild-derived natural recombinant MHC haplotypes. Cross-over site mapping and the identification of a 1.0-kb E beta deletion in the p and w14 haplotypes.
Authors: Soper L A , Stein M B , Passmore H C 
Published: December 2022

Abstract
Detailed molecular analysis of three wild-derived MHC haplotypes provided evidence for an important role of the E beta recombinational hot spot in the recent evolution of the mouse I region. Examination of RFLP and restriction maps of cloned DNA permitted the mapping of the natural cross-over events in the haplotypes carried by strains B10.GAA37 (w21) and B10.KPB128 (w19) to a fragment of DNA not exceeding 4.1 kb, which lies almost entirely within the intron separating the beta 1 and beta 2 exons of the E beta gene. In the w14 haplotype (strain B10.STC77), which appears to be a natural recombinant between a p-like parental haplotype and another wild-derived haplotype, the site of crossing over can be mapped to a segment between the beta 2 exon of the E beta gene (left border) and the E beta 2 gene (right border). This segment containing the cross-over site in the w14 haplotype includes the E beta hot spot. In addition, the w14 haplotype as well as the standard p haplotype contain a deletion of approximately 1.0 kb in the second intron of the E beta gene, which may represent the product of an unequal cross-over event in a E beta recombinational hot spot.
T11/CD2 activation of cloned human natural killer cells results in increased conjugate formation and exocytosis of cytolytic granules.
Authors: Schmidt R E , Caulfield J P , Michon J , Hein A , Kamada M M , MacDermott R P , Stevens R L , Ritz J 
Published: December 2022

Abstract
The T11 (CD2) antigen has been found to be an alternate pathway for antigen-independent activation of resting T cells. T11 triggering also results in activation of NK cells and enhancement of their cytolytic function. The present studies were carried out to further define the mechanisms whereby cytotoxicity is enhanced after T11 activation. A series of clonal human NK cell lines were analyzed after incubation with monoclonal anti-T112 and anti-T113 antibodies specific for different epitopes of the CD2 protein. Anti-T112/3 triggering resulted in increased cytotoxicity against a variety of target cells. Similar results were obtained with F(ab')2 fragments of anti-T112/3, indicating that this effect was not mediated through binding of FcR. The induction of cytotoxicity was found to be associated with increased formation of effector cell-target cell conjugates and with release of secretory granule-localized 35S-labeled proteoglycans. Both enhanced conjugate formation and cytotoxicity could be blocked by anti-lymphocyte function-associated antigen (LFA-1) mAb. Ultrastructural analysis of NK cells after T11 activation demonstrated increased adherence of effector cells to targets and other NK cells as well as a directional reorientation of cytoplasm and intracellular granules toward the area of contact between cells. Discharge of granules occurred into pockets bounded by closely apposed plasma membranes. In the presence of anti-LFA-1 and anti-T112/3, the close apposition and formation of pockets between effector cells and target cells did not occur but the cells exocytosed their intracellular granules. T11 activation of NK cloned cells also resulted in the formation of the homotypic conjugates and autocytotoxicity. As seen with resistant allogeneic targets, autocytotoxicity was mediated by F(ab')2 fragments of T112/3 antibodies and could be blocked by anti-LFA-1 antibody. Ultrastructural analysis of NK cloned cells after T11 activation confirmed the presence of homotypic conjugates with reorientation of effector cells toward one another and discharge of cytolytic granules into pockets formed between NK cloned cells. Taken together, these results indicate that T11-induced cytolytic function of NK cells is, in part, mediated through increased binding of effector cells and targets and that enhanced conjugate formation is at least in part mediated by the LFA-1 antigen. In addition, T11 activation results in the triggering of the cytolytic mechanism of NK cells and the exocytosis of cytolytic granules and their constituents.
Evidence for IL-2 independent proliferation in human T cells.
Authors: Laing T J , Weiss A 
Published: December 2022

Abstract
Previous models of human T cell proliferation have assumed IL-2 to be largely responsible for the clonal expansion observed after TCR complex (CD3/Ti)-mediated stimulation. By using mAb to the CD3 component of CD3/Ti as well as mAb to other nonpolymorphic T cell surface molecules, we demonstrate T cell proliferation in the absence of detectable IL-2 and define some of the conditions necessary for IL-2 production in vitro. PBL cultured with soluble OKT3 alone or OKT3 plus PMA proliferated nearly equally, but IL-2 was detectable only in the supernatants in the latter condition. RNA blot analyses at 8, 16, and 36 h consistently showed high levels of IL-2 transcripts in the OKT3 + PMA stimulated cells. In contrast, when stimulated with OKT3 alone IL-2 transcripts were barely detectable at the 8-h time point only. Anti-Tac only partially inhibited proliferation induced by either OKT3 or OKT3 + PMA, but consistently prevented it when PBL were stimulated by PMA plus exogenous human rIL-2. Cyclosporin A (CsA) was added in varying doses to PBL cultured in the presence of OKT3 + PMA. At 0.05 microgram/ml, proliferation was only partially inhibited, whereas IL-2 was undetectable. To examine the possibility that IL-4 could account for the observed proliferative response, CsA was added to PBL cultured with either OKT3 alone or OKT3 and PMA. Although IL-4 transcript levels were detectable in the presence of OKT3 alone or OKT3 + PMA, CsA at 0.05 microgram/ml allowed proliferation to occur in the absence of detectable IL-2 as well as IL-2 and IL-4 transcripts. Finally, T cell-enriched PBL were shown to proliferate and also to produce substantial quantities of IL-2 in response to immobilized OKT3 + either OKT11 or 9.3. These results strongly suggest the existence of an IL-2 and IL-4 independent pathway of human T cell proliferation and demonstrate that IL-2 production may result only when a closely defined set of stimuli are present.