bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression and function of CD7 molecule on human natural killer cells.
Authors: Rabinowich H , Pricop L , Herberman R B , Whiteside T L 
Published: December 2022

Abstract
The CD7 molecule, one of the earliest T-lymphocyte Ag expressed during ontogeny, has recently been demonstrated to facilitate activation of T cells and to preferentially activate TCR-gamma/delta + subset of T cells. The CD7 Ag is also expressed on human NK cells, but its function has not been determined. In this study, expression and function of CD7 Ag on highly enriched NK cells (94 +/- 3% mean +/- SD, n = 12) obtained by negative selection from peripheral blood of normal donors were investigated. The CD7 Ag was found to be expressed at a significantly (p &lt; 0.002) higher level on fresh NK cells than on IL-2-activated, NK cells. CD7 on human NK cells was found to be a signal-transducing molecule with a rapid increase in cytoplasmic free calcium observed on binding of anti-CD7 mAb to the surface of NK cells. Cross-linking of CD7 induced expression of surface activation molecules such as CD25, CD71, HLA-DR, CD69, and CD54. Activation by anti-CD7 mAb cross-linked to plastic or through goat anti-mouse Ig also induced a variety of NK cell functions: it stimulated secretion of IFN-gamma, led to proliferation of NK cells, as measured by [3H]thymidine incorporation, and significantly enhanced cytotoxicity of NK cells against K562 targets (p &lt; 0.03). However, CD7 on NK cells did not seem to transduce a lytic signal, because it neither mediated redirected killing of Fc gamma R+ murine mastocytoma P815 cells nor triggered lysis of a hybridoma expressing the antibody in a membrane-bound form. CD7 molecules appeared to have a regulatory role in adhesion of NK cells to fibronectin, because cross-linking of CD7 on resting NK cells significantly augmented their adhesion to fibronectin-coated plastic surfaces. However, this induced adhesion was not associated with increased expression of beta 1-integrins on NK cells. Thus, CD7-mediated signals appear to augment function of adhesion molecules on NK cells, which may be involved in NK cell activation by providing both anchorage and costimulatory triggering.
Functional analysis of human Fc gamma RII (CD32) isoforms expressed in B lymphocytes.
Authors: Van Den Herik-Oudijk I E , Westerdaal N A , Henriquez N V , Capel P J , Van De Winkel J G 
Published: December 2022

Abstract
The low affinity IgG receptor Fc gamma RII (CD32) represents the most widely distributed class of human Fc gamma R. To analyze the biologic functions of different Fc gamma RII isoforms, we stably transfected Fc gamma RIIb1, IIb1*, IIb2, IIa, and a IIa tail- mutant to the mouse IIA1.6 B lymphoma cell line. Of these, Fc gamma RIIb1* represents a receptor variant that is identical to IIb1 except for a single amino acid difference in the cytoplasmic tail (amino acid position 11) where a tyrosine (IIb1) is replaced by an aspartic acid (IIb1*). Evaluation of capping ability showed the Fc gamma RIIb1 molecules to cap effectively, which was even more apparent with IIb1*. None of the Fc gamma RIIa, IIa tail-, or IIb2 isoforms capped significantly. Internalization of Fc gamma R-antibody complexes proved very efficient for both the Fc gamma RIIa and IIb2 isoforms, whereas the IIb1 molecules internalized moderately compared with IIb1*, which internalized less efficiently. Notably, human IgG aggregates were internalized effectively by Fc gamma RIIa and moderately by IIb2. Neither Fc gamma RIIb1 nor IIb1* proved capable of internalizing such IgG aggregates. Cross-linking of the different Fc gamma R molecules showed Fc gamma RIIa capable of triggering increases in [Ca2+]i. Fc gamma R expressed on B cells were able to down-regulate [Ca2+]i on co-cross-linking with slgG. Notably, all three Fc gamma RIIb receptors proved active in this respect, in contrast to Fc gamma RIIa. The cell distribution of these Fc gamma RII isoforms was analyzed in a panel of human B cell lines to complement the IIA1.6 B cell model. Fc gamma RIIa was found expressed both at message and protein levels in all tested human B cell lines. In the pre-B cell lines evaluated, no Fc gamma RIIb molecules were detectable, whereas both Fc gamma RIIb1 and IIb2 molecules were found present in more mature B cell lines. These data support both a complex expression pattern of Fc gamma RII isoforms in B cell lines and functional differences between these B cell molecules.
Expansion/deletion of mature T cells exposed to endogenous superantigens in vivo.
Authors: Webb S R , Hutchinson J , Hayden K , Sprent J 
Published: December 2022

Abstract
Previous studies have shown that in thymectomized hosts exposure of mature T cells to Mlsa (mtv-7) Ag in vivo leads to specific tolerance and the disappearance of Mlsa-reactive V beta 6+ T cells after an initial phase of T cell expansion. To investigate the factors controlling postthymic elimination of mature T cells, we examined T cell responses to Mlsa and other endogenous superantigens in a number of different strain combinations. The results show that the extent of T cell expansion/deletion is influenced by various factors, including the H-2 haplotype of the host and the particular V beta studied. Collectively, the results suggest that the extent of elimination of mature T cells is variable and may be a function of high avidity interactions with APC.
Endogenous peptides with distinct amino acid anchor residue motifs bind to HLA-A1 and HLA-B8.
Authors: DiBrino M , Parker K C , Shiloach J , Turner R V , Tsuchida T , Garfield M , Biddison W E , Coligan J E 
Published: December 2022

Abstract
Distinct amino acid (aa) residue motifs for peptides binding to HLA-A1 and HLA-B8 were identified by sequence analyses of reversed-phase HPLC fractions containing endogenous peptides derived from these HLA molecules. Fifteen different primary sequences were determined for HLA-A1-associated peptides, 12 of which were nine aa in length. Common features among these peptide sequences were Tyr at the COOH-terminus, a negatively charged aa (usually Glu) at position 3 (P3), and Pro at P4. Twenty-seven different primary sequence assignments were made for HLA-B8-associated peptides, most of which were eight aa in length. Lys, and in a few cases Arg, predominated at P3 and P5; Leu and Pro predominated at P2, and Leu was the preferred COOH-terminal residue. Unlike all other human class I molecules whose peptide-binding properties have been studied, both HLA-A1 and HLA-B8 endogenous peptide sequences have a dominant anchor residue at P3, and these aa are opposite in charge to the aa at position 156 of the peptide-binding site. Synthetic peptides corresponding to endogenous peptide sequences bound to their respective HLA molecules in vitro, indicating that they derive from peptides bound to HLA and not from copurifying contaminants. Eight of the HLA-A1 and HLA-B8 endogenous peptide sequences matched intracellularly expressed proteins found in protein sequence data bases. The HLA-A1 peptide-binding motif was then used to identify potential antigenic peptides from influenza A viral proteins that bound to HLA-A1 in vitro.
Structural analysis of the human VH locus using nonrepetitive intergenic probes and repetitive sequence probes. Evidence for recent reshuffling.
Authors: Matsumura R , Matsuda F , Nagaoka H , Fujikura J , Shin E K , Fukita Y , Haino M , Honjo T 
Published: December 2022

Abstract
The organization and evolution of the 0.8-Mb JH-proximal region in the human Ig VH locus were studied by mapping DNA fragments hybridized to non-repetitive intergenic probes and by determination of the content and distribution of repetitive sequences. Southern blot analysis of cloned DNA covering the 0.8-Mb region with intergenic probes allowed us to map two to seven cross-hybridizing fragments by each probe. Clusters of fragments detected by an identical set of probes appeared repeatedly within the 0.8-Mb JH-proximal region. Distantly located VH segments flanked by a cluster of DNA fragments hybridized by the same set of probes were highly homologous to each other, providing evidence for recent frequent duplication and translocation throughout the locus. DNA fragments detected by the same set of probes were orientated with the same 5' to 3' order within the cluster, suggesting little involvement of inversion upon recombination in the locus. The content of interspersed Alu and L1 sequences in the VH locus were not significantly greater than the average in the genome.
Cerebral expression of multiple cytokine genes in mice with lymphocytic choriomeningitis.
Authors: Campbell I L , Hobbs M V , Kemper P , Oldstone M B 
Published: December 2022

Abstract
The simultaneous expression of multiple cytokine genes was examined within the brain and peripheral organs of euthymic and congenic athymic mice during the course of lymphocytic choriomeningitis (LCM) induced by the intracranial inoculation of LCM virus. In euthymic mice, levels of TNF-alpha, IL-1 alpha, IL-6, and IL-1 beta mRNA in the brain increased early in infection and further increased with the progression of disease; the level of IFN-gamma mRNA was expressed at high levels late in infection and correlated with the onset of clinical disease. In the peripheral organs, TNF-alpha, IL-1 alpha, and IL-1 beta gene expression predominated early and then declined late in disease. In athymic mice (which do not develop LCM), expression of TNF-alpha, IL-1 alpha, IL-6, and IL-1 beta mRNA increased progressively in brain and peripheral organs from days 3 to 6 postinfection. The levels of these transcripts were significantly lower than those in infected euthymic animals. In euthymic mice, in situ hybridization revealed IFN-gamma-, TNF-alpha-, and IL-1 alpha-expressing cells throughout the inflammatory cell infiltrates associated with areas of LCMV nucleic acid. Therefore, in mice with LCM there is simultaneous expression of multiple cytokine genes, the pattern of which is distinct for brain vs peripheral organs and for euthymic vs athymic mice. The close spatiotemporal relationship between expression of cytokine genes and evolution of disease in brain implicate cytokines are not only key coordinators of the host response but also as possible mediators of neuropathology in LCM.
Taxol provides a second signal for murine macrophage tumoricidal activity.
Authors: Manthey C L , Perera P Y , Salkowski C A , Vogel S N 
Published: December 2022

Abstract
The anticancer drug, taxol, blocks cell division by stabilizing microtubules. However, taxol has distinct cell-cycle-independent effects. For example, taxol and bacterial LPS induce strikingly similar responses in murine macrophages. Here we report that taxol, like LPS, provides a "second" signal for murine macrophage activation to tumoricidal activity. Tumoricidal activity was determined by the release of 51Cr from prelabeled P815 mastocytoma target cells. Taxol or LPS alone weakly induced C3H/OuJ (Lpsn) murine macrophages to kill P815 mastocytoma cells, and tumoricidal activity was not induced by the classic "priming" signal, IFN-gamma. However, combinations of taxol or LPS with IFN-gamma synergized to activate macrophages to lyse tumor cells. Taxol activation of macrophages required an intact LPS signaling pathway, as taxol did not induce IFN-gamma-treated C3H/HeJ (Lpsd) macrophages to lyse target cells. In normal (Lpsn) murine macrophages, IFN-gamma, LPS, or taxol alone induced low or moderate levels of nitric oxide synthase gene expression and nitric oxide secretion. However, this gene and cytostatic metabolite were induced synergistically by combinations of taxol or LPS with IFN-gamma. Secretion of nitric oxide correlated with tumor cell killing, and taxol-activated macrophages failed to kill tumor targets in the presence of NG-monomethyl-L-arginine, a competitive inhibitor of nitric oxide synthase. The data illustrate the potential for taxol to activate macrophage mediated-antitumor mechanisms in addition to its better characterized role as an anti-mitotic agent.
Identification of autoantibody epitopes of glutamic acid decarboxylase in stiff-man syndrome patients.
Authors: Li L , Hagopian W A , Brashear H R , Daniels T , Lernmark A 
Published: December 2022

Abstract
Stiff-man syndrome is a neurologic disorder characterized by progressive rigidity of skeletal muscles. Deficiency of the neurotransmitter gamma-aminobutyric acid and autoantibodies to glutamic acid decarboxylase (GAD), the enzyme synthesizing gamma-aminobutyric acid, are closely associated with the disorder, although the relevant antigenic epitopes have not been identified. In the present study, sera from two patients with SMS was used in an immunoblotting assay with recombinant GAD67 (M(r) 67,000) and GAD65 (M(r) 65,000) isoforms to test whether SMS sera can recognize specific epitopes. We found that both SMS sera recognized the GAD65, but not the GAD67, isoform. Using 13 different synthetic GAD peptides to block the autoantibodies, two GAD65 epitopes were identified. One epitope recognized by both patients' sera, was blocked by the peptide representing amino acid residues 354-368. In one patient only, blocking was also observed by a peptide representing residues 390-402, which includes the binding site of the GAD cofactor, pyridoxal 5'-phosphate. A single amino acid substitution in GAD65 at position 401 (leucine to proline) and representing the analogous GAD67 sequence in this region significantly reduced the peptide's inhibitory effect. These findings suggest that SMS GAD autoantibodies share distinct GAD65 linear epitopes and that some SMS patients' autoantibodies may block the active site, explaining SMS GABA deficiency.
Expression of Mtv-7 sag gene in vivo using a retroviral vector results in selective inactivation of superantigen reactive T cells.
Authors: Kang J , Ido E , Pawling J , Beutner U , Huber B T , Hozumi N 
Published: December 2022

Abstract
T cells expressing specific TCR V beta chains are intrathymically eliminated in mice expressing the murine Mls (minor lymphocyte stimulating) superantigens. Recently, in vitro studies have shown that the endogenous mouse mammary tumor virus (MMTV)-7 sag gene encodes Mls-1 Ag. The demonstrated ability of MMTV superantigen proteins to react with TCRs has led to the postulate that other infectious retroviruses may use superantigen-like molecules to modify the host's immune system. In this report, successful retrovirus-mediated Mtv-7 sag gene transfer into pluripotent hematopoietic stem cells is described. In two different strains of Mls-1- host mice (CBA/Ca and BALB/c) reconstituted with Mtv-7 sag gene expressing bone marrow cells, low levels of ectopic Mtv-7 sag gene expression on syngeneic donor hematopoietic stem cell-derived population alone can induce partial clonal deletion of Mls-1 reactive V beta 6+ and V beta 8.1+ T cells, and complete clonal inactivation of V beta 8.1+ T cells.
Redox mechanism as alternative to ligand binding for receptor activation delivering disregulated cellular signals.
Authors: Nakashima I , Pu M Y , Nishizaki A , Rosila I , Ma L , Katano Y , Ohkusu K , Rahman S M , Isobe K , Hamaguchi M 
Published: December 2022

Abstract
Cross-linking with specific ligand is a general requirement for ordered activation of cell surface receptors. In this study we demonstrated a novel pathway for disregulated receptor activation through a redox mechanism. Treatment of murine thymocytes or spleen cells with thiol-reactive HgCl2, a known inducer of autoimmune proliferative lymphocyte disorders in rodents, was found to induce tyrosine phosphorylation of several cellular proteins, which was up to 100 times as extensive as that triggered by stimulation with antireceptor antibody or mitogen. Through the cross-linkage by thiol-reactive bivalent mercury, transmembrane CD4, CD3, and CD45 and glycosylphosphatidylinositol-anchored Thy-1 were aggregated together on thymocytes or T lymphocytes. Along with the aggregation of Thy-1 and CD4, nonreceptor protein tyrosine kinase p56lck was aggregated and activated. These events were linked to extensive protein tyrosine phosphorylation, which was visualized as a well localized spot beneath the membrane. Under appropriate conditions, this novel pathway of multiple receptor aggregation delivered a disregulated signal into T lymphocytes, which cross-talked to the antireceptor antibody-induced signal, for prolonged cell proliferation and IL-2 production. These results suggest a novel mechanism of disregulation of the ligand-dependent receptor function.
The novel mAb QR6.6 detects a surface molecule on immature thymocytes and inhibits their proliferation on thymic epithelial cells.
Authors: Tamura H , Kuzuhara H , Takeuchi T , Yamamoto H 
Published: December 2022

Abstract
We previously reported that the nude mouse-derived splenic T cell clone N-9F exhibits a proliferative response when cultured on thymic stromal cells. This N-9F proliferation is mediated by direct cell-to-cell interactions between T and thymic stromal cells. A thymic epithelial cell clone, SL10.3, also supports N-9F growth. To identify the molecule involved in T cell development in the thymus, we established mAb specific to the N-9F clone. One of these mAb, QR6.6, was found to inhibit the N-9F proliferative response on SL10.3. QR6.6-positive cells were detected in thymus but not in other lymphoid organs such as bone marrow, lymph nodes, or spleen. QR6.6-positive cells accounted for 3 to 5% of the cells in adult thymuses whereas higher percentages were found in neonatal (10-20%) and fetal thymuses (70% at E17 and 10-20% at E15). The positive cells were primarily CD4-8- thymocytes in fetuses and CD4-8- to CD4+8+ thymocytes in adults. The QR6.6 mAb precipitates a 100 kDa molecule from the N-9F clone. The addition of the mAb to fetal thymus organ culture reduces the recovery of cells at culture day 4. It was also found that the mAb inhibits fetal thymocyte proliferation on the SL10.3 thymic epithelial cell line. These results suggest that the 100 kDa molecule detected by the QR6.6 mAb may play a crucial role in the early stage of thymocyte development.
Stimulator cell type influences the response of T cells to staphylococcal enterotoxins.
Authors: Yagi J , Uchiyama T , Janeway C A 
Published: December 2022

Abstract
Responses to the superantigen Mls are characterized by proliferation of a significant percentage of T cells expressing receptors encoded by one or a few V beta gene segments. Apparently similar responses are elicited by the staphylococcal enterotoxins (SEs) and other bacterial superantigens. We have observed that T cells can be stimulated by the bacterial superantigen SEs presented by either spleen cells or fibroblasts transfected with the appropriate MHC class II genes. However, the results in this study showed that T cells required more than 100-fold higher concentrations of SEA in the presence of L cell transfectants than spleen APC, although T cell responses to SEB and several other toxins presented by the two types of APC were equivalent. Thus, L cell transfectants have a selective defect in presenting SEA. These data suggest that fibroblasts lack a component required by SEA to stimulate certain T cells, and lead us to propose an alternative model for bacterial superantigen mitogenesis in which the superantigen binds to and modifies the behavior of an endogenous co-ligand.
Mechanism of differential regulation of IL-2 in murine Th1 and Th2 T cell subsets. 1. Induction of IL-2 transcription in Th2 cells by up-regulation of transcription factors with the protein synthesis initiation factor 4E.
Authors: Barve S S , Cohen D A , De Benedetti A , Rhoads R E , Kaplan A M 
Published: December 2022

Abstract
Regulation of IL-2 gene expression in response to receptor-mediated stimuli is known to be mediated primarily by the IL-2 transcriptional enhancer and multiple transcription factors. However, the mechanism that controls the differential expression of the IL-2 gene in both human and murine CD4+ Th cell subsets (Th1-IL-2+ and Th2-IL-2-) is not clearly understood. Differential IL-2 gene expression was assessed in murine Th1 and Th2 subsets by analyzing the expression of a Escherichia coli lacZ reporter gene under control of the human IL-2 enhancer (IL2ZH) transfected in both T cell subsets. Stimulation of transfected T cells with the mitogen Con A, anti-CD3 Ab, or PMA plus ionomycin activated the IL2ZH construct in Th1 but not Th2 cells. However, IL2ZH was activated in stimulated Th2 cells that were co-transfected with a vector that overexpressed the eukaryotic initiation factor 4E (eIF-4E). It has been shown that eIF-4E is rate limiting for protein synthesis and its overexpression leads to increased rates of protein synthesis. Hence, eIF-4E overexpression could have overcome a deficiency in transcriptionally active levels of IL-2 regulatory factors in Th2 cells leading to IL-2 enhancer activation. This possibility was supported by demonstrating that transcriptionally active levels of the critical IL-2 transcription factor, nuclear factor of activated T cells (NF-AT), occurred only in Th2 cells overexpressing eIF-4E but not in normal Th2 cells, thus indicating that the inability of Th2 cells to express IL-2 was associated with inadequate levels of at least one transcription factor, NF-AT. Moreover, these results were confirmed by the observation that eIF-4E overexpression augmented NF-AT binding activity in Th2 cells. These data suggest that concentrations of inducible transcription factors are a major component of the regulatory mechanisms dictating IL-2 expression and may be under translational control in Th1/Th2 T cell subsets.
The mouse CD69 gene. Structure, expression, and mapping to the NK gene complex.
Authors: Ziegler S F , Levin S D , Johnson L , Copeland N G , Gilbert D J , Jenkins N A , Baker E , Sutherland G R , Feldhaus A L , Ramsdell F 
Published: December 2022

Abstract
CD69 is a rapidly induced T cell activation Ag that is also expressed in an inducible fashion on cells of most, if not all, hematopoietic lineages. Molecular cloning has shown that CD69 is a type II membrane glycoprotein that is a member of the C-type lectin family. In this report we have shown that induction of CD69 mRNA in activated murine thymocytes and T cells is very rapid, peaking between 30 and 60 min poststimulation, and transient, dropping to nearly resting levels by 8 h. An analysis of the mouse CD69 gene structure showed the gene to consist of 5 exons and have a phorbol ester-inducible promoter element within the first 700 bp upstream of the start of transcription. Chromosomal mapping placed the mouse CD69 gene on the long arm of chromosome 6 near the NK gene complex that contains the related NKR-P1 and Ly-49 gene families. The human CD69 gene mapped to chromosome 12p13 near the related NKG2 gene cluster and in a region associated with rearrangements in approximately 10% of cases of childhood acute lymphocytic leukemia.