bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heat shock protects WEHI‐164 target cells from the cytolysis by tumor necrosis factors α and β
Authors: Jäättelä Marja , Saksela Kalle , Saksela Eero 
Published: March 2007

AbstractElevated temperatures and a number of other types of stress induce synthesis of a small number of highly conserved proteins, the heat shock proteins, in a wide variety of cells. The structure and regulation of these proteins have been intensively studied but the question of the function of this universal response has remained unanswered. We studied the effect of heat shock on tumor necrosis factor‐α (TNF‐α)‐ and ‐β (TNF‐β)‐mediated cytolysis of WEHI‐164 clone 13 target cells. One hour pretreatment of target cells at 42°C decreased rTNF‐α‐mediated lysis by 65.3%, 50.5% and 44.8% and TNF‐β‐mediated lysis by 61.9%, 43.2% and 38.9% at cytokine concentrations of 0.5 ng/ml, 5 ng/ml and 50 ng/ml, respectively, in an 18‐h Cr‐release assay. The effect was maximal when TNF‐α was added 1 h after the heat shock and then gradually declined, being almost undetectable after 2 days. This pattern was found to roughly coincide with the kinetics of hsp68, the major heat‐induced protein in murine cells. Heat shock treatment had no protective effect when given 1 h after addition of recombinant TNF‐α. The heat‐induced target cell resistance was not associated with decreased binding of recombinant TNF‐α to its receptor. Inhibition of protein synthesis by cycloheximide diminished this effect by 76% and inhibition of transcription by actinomycin D abolished it completely, suggesting that de novo synthesized, heat‐induced proteins protect target cells from TNF‐mediated lysis in heat shock‐treated WEHI cells.
Suppression of antibody responses to the acetylcholine receptor by natural antibodies
Authors: Sundblad Anne , Hauser Stephen , Holmberg Dan , Cazenave Pierre‐André , Coutinho Antõnio 
Published: March 2007

AbstractSome relationships between “natural” physiological autoreactivity and antibody responses against the acetylcholine receptor (AChR) were investigated. Collections of unselected monoclonal antibodies were derived from nonmanipulated newborn mice of susceptible (BALB.B) and resistant (BALB/c) mouse strains, and screened for reactivity with heterologous AChR. Five in 200 BALB/c but none in 200 BALB.B clones were found reactive. Four of these anti‐AChR antibodies were analyzed for connectivity to nine other antibodies in the same collection, and three of them found to react with a particular natural anti‐idiotype. The functional in vivo significance of such natural idiotypic complementarities in the anti‐AChR response could then be investigated. Treatment of BALB/c newborn animals with low (100 ng) or high (100 μg) doses of natural anti‐idiotype significantly suppressed their anti‐AChR antibody response when immunized as adults. The utilization of natural anti‐idiotype reagents with broad reactivity patterns might overcome the known idiotype heterogeneity of the autoimmune antibody response to AChR and provide a strategy in prophylactic and therapeutic manipulation of disease development.
Schistosoma mansoni‐specific rat T cell clones. II. Different effects of adult worm‐specific T cell clones in immunocompetent and nude infected rats
Authors: Pestel Joël , Dissous Colette , Louis Jacques , Kusnierz Jean‐Pierre , Damonneville Martine , Dessaint Jean‐Paul , Capron André 
Published: March 2007

AbstractThe in vivo functional activities of two highly proliferating helper rat T cell clones (E23 and G5) specific for the excretory‐secretory antigens of Schistosoma mansoni adult worms were investigated. When injected into infected immunocompetent rats, both clones increased the antibody response against the 30–40‐kDa schistosomulum surface antigens, but failed to induce an immune protection. In contrast, when the same clones were injected into infected nude rats, a high degree of protection was obtained. In this latter case the absence of detectable specific antibody response, whether of IgE or IgG isotype, suggested that parasites were destroyed by an antibody‐independent mechanism, i.e. macrophages activation by lymphokines. Indeed supernatants obtained from T cell clones specifically restimulated with schistosome antigens expressed a macrophage activated activity similar to interferon‐γ. Following incubation with these supernatants or with the active fractions, macrophages exhibited a significant schistosomulicidal activity and both clones were shown to transfer an antigen‐specific delayed‐type hypersensitivity reaction to normal rats. Taken together these results demonstrate that, depending on the immune status of the host, antigen‐specific T cell clones can function differently and consequently that one function associated with one type of lymphokine could be favored.
Regulation of immunoglobulin gene expression in trans by phorbol esters
Authors: Mårtensson Inga‐Lill , Iglesias Antonio , Leanderson Tomas 
Published: March 2007

AbstractLipopolysaccharide‐stimulated B cell cultures treated with phorbol‐12,13‐dibutyrate have been shown to down‐regulate their steady state levels of μs RNA while the μm RNA remained constant. In contrast, the steady state levels of δ RNA was upregulated by the same treatment. By using mice transgenic for a rearranged μ or δ gene, it could be shown that the down‐regulatory effect acts in trans on a defined DNA stretch and is independent of isotype. Thus, the positive effect on endogenous δ RNA steady‐state levels must be regulated at the level of RNA processing. In addition, a DNA construct containing 1.5 kb of a ϵ promoter 5′ of, and an IgH enhancer 3′ of, a chloramphenicol acetyl transferase reporter gene could be down‐regulated in trans by anti‐μ or phorbol‐12,13‐dibutyrate treatment, showing that transcriptional control of Ig promoter elements can readily be observed in non‐transformed B lymphocytes.
Physical linkage of variable, diversity and joining gene segments in the immunoglobulin heavy chain locus of the mouse
Authors: Christoph Thomas , Krawinkel Ulrich 
Published: March 2007

AbstractThe variable region of antibody heavy chains is encoded by multiple variable (V), diversity (D) and joining (J) gene segments which seem to be assembled in a programed developmental pathway during the maturation of B lymphocytes. A physical map linking V, D and J gene segments in the a haplotype of the murine Igh locus is presented in this report. The V gene located next to the known D and J gene segments maps 80 kb upstream of the JH locus and is a member of the VGAM3.8 V gene family. There is evidence for as yet unknown D gene segments located 5′ to this V gene.
Differences in the synthesis and kinetics of release of interleukin 1α, interleukin 1β and tumor necrosis factor from human mononuclear cells
Authors: Lonnemann Gerhard , Endres Stefan , Meer Jos W. M. Van Der , Cannon Joseph G. , Koch Karl M. , Dinarello Charles A. 
Published: March 2007

AbstractCell‐associated and secreted interleukin 1α (IL 1α), IL 1β and tumor necrosis factor α (TNF‐α), produced by human mononuclear cells (MNC) in vitro in response to lipopolysaccharide, were measured by radioimmunoassay. After 18 h of incubation, total production of IL 1α in medium containing 1% heat‐inactivated serum was two‐to‐three times higher than IL 1β. However, in the presence of 1% serum and 5% fresh plasma, IL 1α and IL 1β were produced in similar amounts. Independent of the culture conditions, 90% of the IL 1α remained cell associated whereas 80% of IL 1β was extracellular. The kinetics of production and release of IL 1α, β and TNF‐α were also studied. IL 1α and TNF‐α reached maximal levels within 6 h of stimulation, whereas IL 1β reached maximal levels between 12 and 16 h. IL 1α remained primarily cell associated (80%) for the first 24 h. After 48 h, extracellular IL 1α exceeded cell‐associated levels. IL 1β was primarily secreted (80%), appearing in the extracellular fluid within 6 h. TNF‐α appeared in the extracellular fluid within 1 h of incubation, with < 10% cell associated at any time during the 48 h of incubation. Although the three cytokines share many biological activities, this study provides evidence that MNC IL 1α is predominantly a cell‐associated cytokine acting on a cell‐cell basis, whereas IL 1β and TNF‐α are secreted as paracrine mediators.
Multiple subsets of HIV‐specific cytotoxic T lymphocytes in humans and in mice
Authors: Chenciner Nicole , Michel Frédérique , Dadaglio Gilles , Langlade‐Demoyen Pierre , Hoffenbach AgnèS , Leroux AléNa , Garcia‐Pons Francisco , Rautmann Guy , Guy Bruno , Guillon Jean‐Marcel , Mayaud Charles , Girard Marc , Autran Brigitte , Kieny Marie‐Paule , Plata Fernando 
Published: March 2007

AbstractThe human immunodeficiency virus type 1 (HIV‐1) induces a strong cytotoxic T lymphocyte (CTL) response in humans following infection. HIV‐specific CTL can be detected directly in the blood and lungs of infected patients, and can be expanded in vitro by stimulation with autologous HIV‐infected lymphoblasts. Furthermore, CTL specific for HIV envelope glycoprotein gp160 have been obtained in mice by immunization with recombinant vaccinia virus (VV) that carry the HIV env gene. In this study, we show that mice also produce strong CTL responses to gag and nef proteins following immunization with VV recombinants, thus providing a convenient model system to study T lymphocyte immunity to defined HIV antigens. To determine the specificity of circulating HIV‐immune CTL in humans, a panel of doubly transfected mouse P815 tumor cells was produced which express the human HLA‐A2 or HLA‐A3 transplantation antigen gene and one HIV‐1 gene (env, gag or nef). Using these cells as targets to CTL, we show that HIV‐infected humans carry co‐existing CTL sub‐populations of different specificities. Each subpopulation appears to vary in intensity among different individuals. Surprisingly, CTL specific for regulatory, non‐structural nef protein appear to be a major constituent of the human immune response to HIV.
cDNA cloning of functional T cell receptor γ/δ chains expressed in human peripheral blood lymphocytes
Authors: Mami‐Chouaib Fathia , Jitsukawa Setsuko , Faure Florence , Vasina Bruno , Genevee Catherine , Hercend Thierry , Triebel FréDéRic 
Published: March 2007

AbstractWe have identified in earlier studies two Vδ rearrangements corresponding to a 4.5‐kb Eco RI fragment detected with a Vδ1 probe and to a 7‐kb Eco RI band detected with a Vδ2 probe. These rearrangements have been found in two human T cell clones, F6C7 and G6, displaying surface phenotypes unfrequent in human peripheral blood, namely TiγA+ BB3‐ (F6C7) and TiγA‐ BB3+ (G6). Herein, we report the sequences of the functional transcripts encoded by these rearranged genes and show that the 4.5‐and the 7‐kb Eco RI fragments correspond to V1/D3/Jδ3 and to V2/D3/Jδ3 recombinations, respectively. In addition, we have sequenced the V2/D3/J1/Cδ transcripts expressed in two clones, AB12 and VTC, which have a TiγA+ BB3+ surface phenotype corresponding to that of most γ/δ peripheral lymphocytes. Analyses of the δ transcripts expressed by these four cells further strengthen the hypothesis that anti‐BB3 and anti‐δ‐TCS‐1 monoclonal antibodies recognize a Vδ2‐ and a V1/(D)/Jδ1‐encoded epitope, respectively. Sequence of the γ transcripts expressed by AB12 and F6C7 cells shows that they encode a V9/JP/Cγ1 chain. Finally, we confirm that non‐combinatorial diversity in the γ and δ proteins is generated by both junctional flexibility and N‐region addition without any somatic mutation.
Characterization of three functional sites in αβ1 DR of DRw13. all three sites are potentially involved in major histocompatibility complex‐peptide interaction
Authors: Sterkers Ghislaine , Tiercy Jean‐Marie , Zeliszewski Dominique , Levy Jean‐Paul , Mach Bernard 
Published: March 2007

AbstractAn HLA‐DR product encoded by the HLA‐DRw13/Dw19 haplotype has been identified as the HLA class II molecule involved in antigen presentation to several influenza‐specific helper T cell clones. Three different functional sites were identified on this molecule by comparing the structure of HLA‐DR products of known sequences and their ability to efficiently present foreign antigen to the T cell clones. These functional sites were mapped on the recently proposed three‐dimensional structure of HLA class II molecules. From their position, these sites are all potentially involved in HLA‐peptide interaction and capable of affecting the binding and/or the conformation of the foreign peptide. This suggests that polymorphic residues essential in major histocompatibility complex restriction are mostly involved in peptide binding.
Identification of interleukin 4 receptor‐associated proteins and expression of both high‐ and low‐affinity binding on human lymphoid cells
Authors: Foxwell Brian M. J. , Woerly Gaetane , Ryffel Bernhard 
Published: March 2007

AbstractInterleukin 4 (IL 4) produced by activated T cells expresses its biological effects on T and B lymphocytes by binding to specific membrane receptors. Cross‐linking of human recombinant 125I‐IL 4 to peripheral blood mononuclear cells identifies a trimolecular complex consisting of a 65/70‐kDa doublet and a 110‐kDa protein. Scatchard analysis reveals about 300 IL 4 binding sites/cell on resting cells with an equilibrium binding constant (Kd) of ∼ 100 pM. Stimulation by anti‐CD3 antibodies causes an up‐regulation of IL 4 receptors by a factor of 2 to 3 without any change in binding affinity. In addition to this high‐affinity binding site a second class of a previously unidentified, low‐affinity receptor (Kd ∼ 30 nM, ∼ 9000 sites/cell) is expressed on resting lymphocytes. The number of low‐affinity binding sites for IL 4 also increases twofold upon cell activation. Exogenous IL 4 enhances the expression of its receptor on resting lymphocytes and this effect is further increased by anti‐CD3 activation. Binding of IL 4 to its receptor is specific, being only inhibited by IL 4 and not by IL 2.By contrast, the gibbon leukemia cell line MLA 144 expresses only high‐affinity receptors for IL 4. Cross‐linking studies reveal a 45/50‐kDa IL4 receptor‐associated doublet in addition to the three proteins identified in human peripheral blood mononuclear cells. The functional significance of the different proteins composing the receptor for IL 4 is discussed.
Major histocompatibility complex – dependent T cell epitopes of lymphocytic choriomeningitis virus nucleoprotein and their protective capacity against viral disease
Authors: Schulz Manfred , Aichele Peter , Vollenweider Maja , Bobe Frank W. , Cardinaux Francis , Hengartner Hans , Zinkernagel Rolf M. 
Published: March 2007

AbstractIn mice the immune response to infection with lymphocytic choriomeningitis virus (LCMV), a member of the arenavirus family, is mainly based on the activity of cytotoxic T cells. The immunogenic epitopes of the viral nucleoprotein recognized by cytotoxic T cells in various inbred strains of mice were defined. These epitopes were located in H‐2d and H‐2q mice in the amino‐terminal region and in H‐2b mice in the carboxy‐terminal region of the nucleoprotein. A detailed analysis with synthetic peptides allowed the definition of a common epitope of 9 amino acids in H‐2d and H‐2q mice and of about 15 amino acids in H‐2b mice. These T cell epitopes were all recognized in association with H‐2 D or L transplantation antigen. The protective capacity of recombinant vaccinia viruses expressing these epitopes was documented by assaying prevention of virus replication, protection against LCM and prevention of the local footpad swelling reaction. Thus, distinct T cell epitopes on the same internal viral protein mediate protection in a major histocompatibility complex‐restricted manner.
Interleukin 5 regulation of peritoneal Ly‐1 B lymphocyte proliferation, differentiation and autoantibody secretion
Authors: Wetzel Gayle Delmonte 
Published: March 2007

AbstractThe in vitro effects of recombinant interleukin (IL) 5 on proliferation and maturation of mouse Ly‐1 B cells were studied. Most freshly isolated peritoneal Ly‐1 B cells expressed high levels of IL5 receptor (R). Limiting dilution analyses showed that mitogens could reveal IL5 responsiveness in more than half of low density peritoneal Ly‐1 B cells. IL5 was able not only to increase the proportion of these Ly‐1 B cells induced to proliferate, but it also shifted the clone size distribution of proliferating cells towards larger clone sizes. Splenic Ly‐1 B cells also proliferated in response to mitogens plus IL5. Spontaneous and polyclonal activator‐induced plaque‐forming cell responses of Ly‐1 B cells were increased by IL5. Furthermore, IL 5 increased the frequency of peritoneal Ly‐1 B cells induced to secrete certain autoantibodies. IL5 was certainly the agent responsible since its effects on both proliferation and differentiation were inhibited by either anti‐IL5R monoclonal antibodies or by anti‐IL5 monoclonal antibodies. Hence, Ly‐1 B cells, IL5 and the IL5R appear to constitute a system of cellular proliferation, differentiation and some autoantibody production. Strategies specifically targeting the interleukin and receptor elements of this system might afford external control of these cellular responses.
Elevated temperature regulates tumor necrosis factor‐mediated immune killing
Authors: Gromkowski Stanislaw H. , Yagi Junji , Janeway Charles A. 
Published: March 2007

AbstractThe effect of elevated temperature (heat/fever) on the regulation of inflammatory processes was studied in an in vitro system. Since tumor necrosis factor (TNF), a central mediator in inflammation, is both a pyrogen and a cytokine capable of inducing the death of certain cells, we examined the relationship between heat shock and TNF‐mediated immune killing. Heat shock of WEHI‐164 fibrosarcoma cells significantly (and transiently) decreased the sensitivity of these cells to recombinant TNF‐mediated lysis and to class II major histocompatibility complex‐specific, TNF‐secreting inflammatory T cell‐mediated lysis. Incubating inflammatory T lymphocytes in elevated temperature transiently abolished their lytic potential and their ability to secrete TNF. Our data show that the pyrogen activity of TNF could control cytolytic processes during inflammation both by inducing protective protein(s) synthesis in target cells and by arresting TNF secretion by effector T lymphocytes.
Cyclic AMP can enhance mouse B cell activation by regulating progression into the late G1/S phase
Authors: Li Yue Sheng , Kouassi Edouard , Revillard Jean‐Pierre 
Published: March 2007

AbstractThis study demonstrates that several substances which raise intracellular adenosine 3',5'‐cyclic monophosphate (cAMP) levels in different ways were able to enhance both RNA and DNA synthesis in mouse purified B cells co‐stimulated by the protein kinase C activator phorbol 12‐myristate 13‐acetate and the Ca2+ ionophore ionomycin, while earlier activation events were not modified. These included early changes in cell size and chromatin decondensing demonstrated by light scatter properties at narrow and 90° angles, increase in Ia expression and loss of surface IgD. We concluded that cAMP can up‐regulate mouse B cell activation by controlling progression into the late G1 (G1B)/S phase, but not transition from G0 to early G1 (G1A). Furthermore, because cAMP could synergize with ionomycin but not with phorbol 12‐myristate 13‐acetate to induce RNA and DNA synthesis, we proposed that the cAMP effects in this model may be related to the protein kinase C pathway.
Embryonic neural cell adhesion molecules on human natural killer cells
Authors: Husmann Matthias , Pietsch Torsten , Fleischer Bernhard , Weisgerber Christoph , Bitter‐Suermann Dieter 
Published: March 2007

AbstractThe neural cell adhesion molecules (NCAM) are surface glycoproteins that were first described in brain tissue. NCAM mediate adhesion in a variety of cell‐cell interactions. In the present study we show that the so‐called “embryonic” NCAM, i.e., the highly polysialylated forms of these proteins, are expressed on natural killer cells and some CD3+ cells in man. Homotypic binding of NCAM, believed to be of importance for cell‐cell adhesion in neural tissues, appears not to be essential for NK cell‐mediated killing. Yet, NCAM might be involved in NK cell migration, homing or related functions.
Human complement factor H: An additional gene product of 43kDa isolated from human plasma shows cofactor activity for the cleavage of the third component of complement
Authors: Misasi Roberta , Huemer Hartwig P. , Schwaeble Wilhelm , Sölder Elisabeth , Larcher Clara , Dierich Manfred P. 
Published: March 2007

AbstractIn addition to the 150‐kDa factor H protein, we have previously described a 43‐kDa factor H molecule in human plasma, which probably represents a translational product of the additional 1.8‐kb mRNA for factor H. This factor H was isolated from human plasma by means of immunoaffinity chromatography and high‐performance liquid chromatography. When tested for its functional activity, this purified 43‐kDa H protein was shown to act as cofactor for factor I ‐ mediated cleavage of fluid‐phase C3b to iC3b.
Internalization of ige receptors on rat basophilic leukemic cells by phorbol ester. comparison with endocytosis induced by receptor aggregation
Authors: Ra Chisei , Furuichi Kiyoshi , Rivera Juan , Mullins J. Michael , Isersky Chaviva , White Kenneth N. 
Published: March 2007

AbstractPhorbol myristate acetate (PMA) can induce a rapid and significant decrease in the expression of IgE receptors on RBL‐2H3 cells. Fluorescence microscopy confirmed that the down‐regulation is due to internalization of receptors. The endocytotic response to PMA shares several characteristics with endocytosis induced by immunochemical aggregation of surface‐bound monomeric IgE: the rates of internalization both have a t1/2 of about 5 min, a maximum of 35% of the surface‐bound IgE can be endocytosed by the action of PMA (50% by receptor aggregation), endocytosis is sustained for at least up to 60 min, neither stimulus requires extracellular Ca2+ and endocytosis induced by either stimulus is an active process, i.e., is dependent on temperature and cellular energy. Biochemical studies revealed some differences between the endocytotic responses to the two stimuli. After prolonged treatment of cells with dexamethasone, only endocytosis induced by PMA is inhibited. Cells depleted of protein kinase C by prolonged exposure to PMA can sustain a significant endocytotic response to aggregation of IgE receptors, but become completely desensitized to PMA. These data suggest that different biochemical pathways mediate the signals from the two stimuli and that protein kinase C is directly involved in endocytosis induced by PMA but does not have a major role in endocytosis induced by receptor aggregation.