bluuebunny/crossref_metadata_2025_split huggingface dataset:
Primary biliary cirrhosis. Inhibition of pyruvate dehydrogenase complex activity by autoantibodies specific for E1 alpha, a non-lipoic acid containing mitochondrial enzyme.
Authors: Fregeau D R , Roche T E , Davis P A , Coppel R , Gershwin M E 
Published: December 2022

Abstract
Antimitochondrial antibodies (AMA) are serologically characteristic of patients with PBC. Four Ag recognized by AMA have been recently identified, including protein X and the acyltransferases of three related multienzyme complexes: the pyruvate dehydrogenase complex (PDC), the branched-chain alpha-ketoacid dehydrogenase complex, and the alpha-ketoglutarate dehydrogenase complex. Each of these enzymes contains one or more lipoyl moieties as part of a major functional site. In addition, epitope mapping has suggested that the AMA target is this lipoic acid-binding region. In this report we demonstrate that sera from patients with PBC also recognize the E1 component (pyruvate dehydrogenase, EC 1.2.4.1) of PDC. PDC-E1 is composed of alpha and beta-chains. Reactivity with the 41 kD alpha chain was detected in 80 of 120 (66%) PBC sera by immunoblotting against purified PDC-E1; 2 of 120 sera also demonstrated reactivity with the 34 kD beta chain. In contrast, sera from patients with SLE, chronic active hepatitis, or progressive sclerosing cholangitis as well as sera from healthy volunteers did not react with PDC-E1. Furthermore, affinity-purified PBC sera against PDC-E1 alpha were able to inhibit PDC enzyme activity, whereas control sera could not. PDC-E1 alpha is now the fifth mitochondrial autoantigen of PBC to be identified. Similar to the four previously identified autoantigens, AMA appear to be directed to a functional site of PDC-E1 alpha inasmuch as they are able to inhibit enzyme function. However, PDC-E1 alpha is also unique in that it is the first identified mitochondrial autoantigen which does not contain lipoic acid.
Defective clonogenic potential of CD8+ T lymphocytes in patients with AIDS. Expansion in vivo of a nonclonogenic CD3+CD8+DR+CD25- T cell population.
Authors: Pantaleo G , Koenig S , Baseler M , Lane H C , Fauci A S 
Published: December 2022

Abstract
This study examines the potential mechanism(s) responsible for the defective clonability of CD8+ T lymphocytes in patients with AIDS. By the combined use of one- and two-color fluorescence cytofluorometry we have shown an increase in the number of circulating DR+ cells due to the expression of DR on a relatively large proportion of T lymphocytes (one-third of CD3+ cells), the majority of them belonging to the CD8+ subset. In addition, the majority of CD8+DR+ cells in AIDS patients did not express CD25 Ag (the receptor for IL-2), a surface marker generally expressed on normal activated T lymphocytes. Sorted CD8+DR+ and CD8+DR- cell populations were analyzed comparatively for their ability to proliferate in response to different stimuli, including anti-CD3, anti-CD2, alone or in combination with anti-CD28 mAb and mitogens such as PHA, alone or in combination with PMA. We have demonstrated that CD8+DR+ cells were severely defective in their proliferative response to triggering via these major pathways of T cell activation even when an exogenous source of IL-2 or IL-4 was added to the microcultures 24 h after initiating the cultures. In contrast, CD8+DR- cells showed a significant proliferation in response to the different stimuli and the proliferative response was strongly enhanced by the addition of IL-2 or IL-4. At the end of the stimulation period CD8+DR+ and CD8+DR- proliferating populations were analyzed for CD25 Ag expression. Only 1 to 10% of CD8+DR+ cells expressed CD25 antigen compared with 40 to 50% of CD8+DR- cells. The proliferative defect of CD8+DR+ cells was further confirmed in experiments performed at the clonal level. The analysis of the frequency of proliferating T lymphocyte-precursors in both CD8+DR+ and CD8+DR- subsets showed that the defective clonogenic potential of CD8+ cells in AIDS patients could be in large part ascribed to CD8+DR+ cells. Five percent of CD8+DR+ cells showed a clonogenic potential compared to the 25% of CD8+DR- cells. Finally, we analyzed the surface expression of VLA-2 Ag, a marker of a chronic state of T cell activation, on circulating T lymphocytes. We have shown that a large proportion of CD3+DR+CD25- cells (50 to 80% in the different patients with AIDS analyzed) expressed VLA-2 Ag.(ABSTRACT TRUNCATED AT 400 WORDS)
IL-3-induced activation of protein kinases in the mast cell/megakaryocyte R6-XE.4 line.
Authors: Pelech S L , Paddon H B , Charest D L , Federsppiel B S 
Published: December 2022

Abstract
A role for second messenger-regulated protein kinases in the early post-IL-3 receptor signal transduction pathway was investigated in the mast cell/megakaryocyte line R6-XE.4. The activity of the calcium- and phospholipid-dependent protein kinase C (PKC) was assessed by the ability of the enzyme to phosphorylate histone H1 in the presence of calcium, diacylglycerol, and phosphatidylserine or after proteolytic activation of PKC with trypsin. In high serum-supplemented cells, but not in cells that were preincubated in serum-deficient media for 6 h, subsequent treatment for 15 min with synthetic IL-3 (10 micrograms/ml) caused up to a sixfold increase in the calcium- and lipid-stimulated histone H1 phosphorylating activity of particulate-associated PKC after fractionation on MonoQ. However, there was no corresponding reduction of cytosolic PKC activity. Therefore, IL-3 appeared to modify the activity of preexisting membrane-associated PKC rather than eliciting its recruitment from the cytoplasm in R6-XE.4 cells. This was in contrast to the situation with FDC-P1 cells, where IL-3 induced PKC translocation. IL-3 also stimulated a cytosolic protein kinase that phosphorylated a synthetic peptide patterned after a phosphorylation site in ribosomal protein S6, but this IL did not alter the activity of cAMP-dependent protein kinase.
CD4+ T cell subsets. Lymphokine secretion of memory cells and of effector cells that develop from precursors in vitro.
Authors: Swain S L , Weinberg A D , English M 
Published: December 2022

Abstract
We have studied the properties of several developmentally defined subpopulations of CD4+ T cells from normal animals which can be stimulated to secrete lymphokines. We find that the Th cells responsible for direct secretion of lymphokines after stimulation are from a resting, very long lived subpopulation of CD4+ T cells which persists for over 25 wk after adult thymectomy. These T cells are depleted by in vivo administration of antithymocyte serum and they are enriched among T cells which express high levels of Pgp-1. This phenotype suggests that the T cells responsible are most likely memory T cells which have resulted from antigen exposure in vivo. T cells in this subset secrete predominantly IL-2 with small quantities of IL-3, granulocyte/macrophage CSF, and IFN-gamma. In contrast, the CD4+ T cells which require in vitro culture and restimulation before they develop into an effector population with the ability to secrete lymphokines after restimulation, differ dramatically by most of these criteria. The precursors we study are resting Th cells which are considerably shorter lived after adult thymectomy (5 to 10 wk) and resistant to the same doses of antithymocyte serum which deplete the putative memory population. We hypothesize that this precursor population represents naive helper cells which have not yet encountered Ag. The effectors derived from such precursors can be stimulated to secrete high levels of both Th cell types 1 and 2 lymphokines (IFN-gamma, IL-4, IL-5, granulocyte/macrophage CSF, and IL-3). Generation of effectors requires proliferation and differentiation events which occur during a mandatory culture with lymphokines and antigen presenting cells for 3 to 4 days. We discuss the striking phenotypic and functional differences among these subpopulations of helper cells--the precursor population and the two types--memory and cultured effector Th which secrete lymphokines. We also discuss the relationship of these populations to CD4+ T cell subsets defined by other studies of patterns of lymphokine secretion and by cell surface phenotype.
The specificity of human anti-cytochrome c autoantibodies that arise in autoimmune disease.
Authors: Mamula M J , Jemmerson R , Hardin J A 
Published: December 2022

Abstract
Cytochromes c (cyt c) are among the best characterized model Ag because their amino acid sequences and tertiary structures are well defined. One unique aspect of cyt c as an immunogen is its ability to induce autoantibody responses in animal models, although no pathology resulting from these responses has been reported. In this study, the presence and specificity of autoantibodies to cyt c were investigated in patients with SLE and related connective tissue diseases. Anti-cyt c antibodies were found in approximately 7% of patient sera and were statistically associated with the expression of antimitochondrial antibodies but were not statistically associated with any disease subset among those represented. Anti-cyt c was not associated with the presence of autoantibodies to DNA, histones, Ro, La, or Sm autoantigens. Most of the autoantibodies were specific for native or native-like forms of cyt c but antibodies to denatured forms were also apparent. Autoantibody binding was shown to be directed predominantly at selected sites of evolutionary variability within cyt c. The specificity of the human anti-cyt c autoantibodies appear to be similar to that of mouse anti-human cyt c antibodies and to autoantibodies elicited in mice against rat (mouse) cyt c.
High-affinity binding of an influenza hemagglutinin-derived peptide to purified HLA-DR.
Authors: Roche P A , Cresswell P 
Published: December 2022

Abstract
Immunogenic peptides have been shown to bind detergent-solubilized class II (Ia) molecules from mice. In this investigation, we report that highly purified HLA-DR (DR) molecules in detergent solution are capable of binding a synthetic peptide (HAp) derived from the influenza hemagglutinin sequence. Although the presentation of this peptide has been demonstrated only to DR1-restricted Th cells, the association rate constants for the formation of HAp-DR1, -DR5, and -DR8 complexes were essentially identical (ka = 1.1 x 10(2) to 1.6 x 10(2) M-1 s-1). By contrast, the value of the rate constants for the dissociation of preformed HAp-DR1, -DR5, and -DR8 complexes varied nearly threefold (kd = 1.6 x 10(6) to 4.4 x 10(-6) s-1). The value of the equilibrium dissociation constants (KD) derived from these rate constants were 13 nM, 24 nM, and 28 nM, for HAp-DR1, -DR5, and -DR8 complexes, respectively. Scatchard analysis demonstrated that the KD obtained from the rate constants for the HAp-DR1 reaction was in excellent agreement with that obtained under equilibrium conditions. SDS-PAGE confirmed that the HAp-DR complexes were remarkably stable, as HAp remained associated with the DR alpha beta heterodimer after treatment of the complexes with SDS and beta-mercaptoethanol. Steady-state binding studies demonstrated that 18% of all DR1 molecules had bound HAp at equilibrium, whereas only 3.8% of all DR8 molecules had bound HAp under identical conditions. The slight differences in the KD for HAp-DR complexes suggest that differences in the affinity of a peptide for DR alleles alone may not always explain the process of MHC restriction.
Virus-specific delayed-type hypersensitivity (DTH). Cells mediating lymphocytic choriomeningitis virus-specific DTH reaction in mice.
Authors: Moskophidis D , Fang L , Gossmann J , Drjupin R , Löhler J , Bruns M , Lehmann-Grube F 
Published: December 2022

Abstract
We had previously shown that the local lymphocytic choriomeningitis virus-induced delayed-type hypersensitivity (DTH) reaction in mice consists of two well delineated phases that are mediated by CD8+ and CD4+ T lymphocytes, respectively. These findings have been confirmed and extended by showing that the first CD8+ cell-dependent part of the response was enhanced by either the presence of CD4+ cells or systemic treatment with IL-2 and that it developed in the absence of detectable numbers of mononuclear phagocytes, whereas the later CD4+ cell part required monocytes or related elements. Furthermore, in the DTH reaction that was elicited with noninfectious viral Ag in mice previously immunized by infection, only the CD4+ cells participated. Thus, the two phases of the lymphocytic choriomeningitis-viral DTH reaction are principally different, which has to be taken into account when trying to assess the relevance of DTH during this virus infection.
Protective effect of recombinant tumor necrosis factor-alpha in murine salmonellosis.
Authors: Nakano Y , Onozuka K , Terada Y , Shinomiya H , Nakano M 
Published: December 2022

Abstract
The enhancement of resistance by i.p. administration of murine rTNF-alpha into mice against i.p. challenge with virulent Salmonella typhimurium was studied. Administration of TNF-alpha (5 x 10(4) U/mouse) into mice at 6 or 12 h before the challenge with S. typhimurium organisms enhanced the bactericidal capacity in the peritoneal cavities of the mice. The diminution of the infecting organism in the peritoneal cavities of the TNF-alpha-treated mice was not due to the systemic spread of the organism inasmuch as few organism were recovered from other areas such as the spleen and liver. The TNF-alpha treatment effected a slight increase of neutrophils in the peritoneal cavity, but did not effect an increase of macrophages, including Ia-bearing macrophages. The survival rate of mice infected with Salmonella was improved by the i.p. injection of TNF-alpha before infection. Co-administration of smaller doses of TNF-alpha (5 x 10(3) U) and murine rIFN-gamma (10(2) U) at 6 h before the challenge also effectively enhanced bactericidal activity and protectivity. The cooperative effect of TNF-alpha and IFN-gamma was only seen when these recombinant cytokines were injected together at the proper time before the challenge. Injection of rabbit anti-TNF-alpha serum abolished the effects of TNF-alpha and the cooperative effect of TNF-alpha and IFN-gamma. Furthermore, the serum could abolish the cooperative effect of IFN-gamma and LPS on bactericidal activity, suggesting participation of LPS-induced TNF-alpha in the cooperation.
The effect of anti-IFN-gamma antibody on the protective effect of Lyt-2+ immune T cells against toxoplasmosis in mice.
Authors: Suzuki Y , Remington J S 
Published: December 2022

Abstract
The effect of an IFN-gamma mAb on the protective activity of immune T cells against Toxoplasma infection was examined in a murine model of toxoplasmosis. Mice that received anti-IFN-gamma antibody and immune spleen cells all died of toxoplasmosis after challenge with Toxoplasma tachyzoites. In contrast, mice that received normal IgG and immune spleen cells all survived the infection. The protective activity of Lyt-2+ immune T cells, previously shown to be the principal mediators of resistance against Toxoplasma in mice was completely ablated by the anti-IFN-gamma mAb. These results suggest that IFN-gamma is the major mediator of the resistance against Toxoplasma infection in mice which is conferred by immune T cells.
Isolation, characterization, and expression of cDNA clones encoding the mouse Fc receptor for IgE (Fc epsilon RII)1.
Authors: Gollnick S O , Trounstine M L , Yamashita L C , Kehry M R , Moore K W 
Published: December 2022

Abstract
We have isolated cDNA clones encoding a mouse low affinity receptor for IgE (Fc epsilon RII) from a cDNA library of BALB/c splenic B cells activated with LPS and IL-4. The 2.2-kb cDNA clone encodes a 331 amino acid membrane glycoprotein that is homologous to human Fc epsilon RII (CD23) and a family of carbohydrate-binding proteins. COS7 cells transfected with the cDNA clones expressed a 45,000 m.w. protein that bound IgE and the anti-Fc epsilon RII mAb, B3B4. Fc epsilon RII mRNA was up-regulated in mouse B cells by culture with IL-4, but not in B cells cultured with IgE. Fc epsilon RII mRNA was detected in IgM+/IgD+ B cell lines, but not in pre-B cell lines or in B cell lines which have undergone differentiation to secrete Ig. The monocyte line P388D1, mast cell lines MC/9 and PT18, and peritoneal macrophages stimulated with IL-4 lacked detectable Fc epsilon RII mRNA, as did Thy-1.2+, CD4+, and CD8+ normal T cells and Thy-1.2+ T cells from Nippostrongylus brasiliensis-infected mice.
The temporal order of appearance of transcripts from unrearranged and rearranged Ig genes in murine fetal liver.
Authors: Lennon G G , Perry R P 
Published: December 2022

Abstract
The developmental time course of RNA transcribed from unrearranged (germ-line) and rearranged Ig genes in murine fetal liver was determined by a quantitative Northern blot analysis. Sterile Cmu transcripts and germ-line VH transcripts are detectable as early as day 14, whereas significant amounts of rearranged VDJCmu H chain transcripts do not appear until days 16 to 17. The sterile Cmu transcripts continuously increase in abundance throughout fetal development, in contrast to the germ-line VH transcripts, which decrease abruptly after day 16. Transcripts of germ-line and rearranged CK genes are detectable on day 17, and continue to increase in abundance on day 18. Transcripts from a pre-B cell specific gene, lambda 5, first appear on day 15, and reach maximum abundance on day 17. The order of these events is consistent with the known order of gene rearrangements and with the idea that transcriptional activation of germ-line loci is a prerequisite for Ig gene rearrangement. The lag between the onsets of germ-line Cmu and VH transcription and the appearance of VDJCmu transcripts suggests that additional developmentally regulated events may be necessary to achieve efficient expression of completely rearranged H chain genes.
Heterogeneity of helper/inducer T lymphocytes. IV. Stimulation of resting and activated B cells by Th1 and Th2 clones.
Authors: Abbas A K , Urioste S , Collins T L , Boom W H 
Published: December 2022

Abstract
To test the hypothesis that resting and previously activated B lymphocytes differ in their proliferative and differentiative responses to various Th cell-derived stimuli, we have examined the interactions of purified small (resting) and large (activated) murine B cells with rabbit Ig-specific Th1 and Th2 clones in the presence of the Ag analogue, rabbit anti-mouse Ig antibody. Small numbers of Th2 cells induce strong Ag-dependent proliferation of and Ig secretion by both resting and activated B lymphocytes. In contrast, Th1 clones stimulate lower responses of activated B cells and fail to stimulate small resting B cells. An interaction with Th1 clones does make small B cells responsive to the Th2-derived cytokine, IL-4, indicating that Th1 clones are capable of delivering some but not all the stimuli necessary for the induction of humoral immunity. Finally, in order to compare the responses of small and large B cells to cognate interactions and secreted cytokines, we used an autoreactive I-Ak-specific Th2 line. This line induces proliferation of and Ig secretion by I-Ak expressing but not H-2d resting and activated B cells as a result of cognate interactions. However, when the H-2d B cells are bystanders in the presence of cytokine secretion by this Th2 line, or are directly exposed to Th2-derived cytokines, both small and large B cells are induced to proliferate but only the large B cells secrete antibody. These results indicate that the magnitude and nature of antibody responses depend on three principal factors: the cytokines produced by Th cells, the state of activation of the responding B lymphocytes, and whether the B cells are recipients of cognate help or are bystanders at the site of T cell stimulation. Our findings also confirm the view that cognate T-B interactions are most efficient for initiating B cell responses and may allow B cells to subsequently respond to a variety of T cell-derived cytokines.
gp33-38, an early human T cell activation antigen.
Authors: Carrel S , Salvi S , Isler P , Rapin C , Hayoz D , Gallay P , Giuffrè L 
Published: December 2022

Abstract
We describe an activation Ag Me14/D12 that appears early after T cell activation and is absent in resting T lymphocytes. Me14/D12 is a nondisulfide-linked heterodimeric structure containing two polypeptide chains of 33,000 and 38,000 Da. The expression of Me14/D12 on resting T lymphocytes can be induced by different activation stimuli such as the lectins PHA and Con A, the phorbol ester PMA, and anti-CD3 mAb. The induction of mRNA for Me14/D12 (gp33-38) in PHA-activated T lymphocytes precedes that of IL-2R gene transcripts by more than 20 h. Me14/D12 mRNA was detectable as early as 2 h after the onset of activation and mRNA for the IL-2R only after 24 h. The surface expression of Me14/D12 was detectable between 12 and 24 h after activation and was maximal between 24 and 48 h. Several T leukemia cell lines express the Me14/D12 Ag. On Me14/D12- cell lines, PMA and IFN-gamma induced surface expression of Me14/D12. Once Me14/D12 Ag were expressed on Jurkat cells after stimulation with either PMA or IFN-gamma, the binding of mAb Me14/D12 induced the production of significant amounts of IL-2 and of Ca2+ mobilization from internal stores. Comparative biochemical studies clearly demonstrate that Me14/D12 (gp33-38) is different from the CD69 molecular complex defined by mAb MLR3 and AIM.
T cell receptor-mediated DNA fragmentation and cell death in T cell hybridomas.
Authors: Odaka C , Kizaki H , Tadakuma T 
Published: December 2022

Abstract
Activation of Ag-specific T cell hybridomas with a high density of immobilized anti-CD3 antibody resulted in not only secretion of IL-2 but also cell death of up to 60 to 80% in selected hybridomas after 14 h. Similar results were obtained with V beta 8+ T cell hybridomas stimulated with cross-linked F23.1 antibody. In these activated hybridomas, we found that DNA was fragmented into 180- to 200-bp multiples. DNA fragmentation was not observed when T cells were maintained after killing with anti-Thy-1 plus C or with heat treatment at 45 degrees C, nor when T cells were incubated with fixed anti-CD4 antibody. Furthermore, fragmentation was detectable at 6 h after incubation when almost all of the cells were still viable as evaluated by trypan blue dye exclusion test. Cell death was prevented by addition of EGTA, cycloheximide, actinomycin D, and zinc, suggesting that the induction of cell death requires Ca2+ influx, newly synthesized protein(s), and involvement of endonuclease.