bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contrasting effects of glucocorticoids on the capacity of T cells to produce the growth factors interleukin 2 and interleukin 4
Authors: Daynes Raymond A. , Araneo Barbara A. 
Published: March 2007

AbstractThe molecular mechanisms which govern the biosynthesis and secretion of the various T cell‐derived lymphokines are poorly understood at this time, in spite of their tremendous importance to the control of the mammalian immune system. Here we provide compelling evidence that production of the murine T cell growth factors interleukin (IL)2 and IL 4 are differentially regulated by glucocorticoid (GCS) hormones. Under conditions where IL 2 production is reduced by GCS hormones, IL 4 production is increased. In vivo, this effect on T cell production of growth factors is manifest at low GCS concentrations that are well within physiologic ranges. In vitro, splenocytes isolated from antigen‐stimulated donors, as well as antigen‐specific cloned T cell lines, undergo alterations in their capacity to secrete T cell growth factors when stimulated with antigens in the presence of GCS. Responses normally dominated by IL 2 are dramatically shifted to a condition where IL 4 represents the major species of T cell growth factor produced. Similar changes in the pattern of T cell growth factor production are observed following short pulses with low‐dose GCS in vitro, and the steroid‐induced depression in IL 2 production can be reversed and/or inhibited by treatment with the potent steroid antagonist RU486. Our results imply that GCS hormones, presumably through their capacity to activate a specified family of ligand‐dependent transcriptional regulatory proteins (steroid hormone receptors), function to control the pattern of lymphokines produced by activated T cells. Steroid‐mediated regulation of lymphokine gene expression could serve to dictate the types of immune effector mechanisms which can be initiated subsequent to antigen exposure.
Cholera toxin modulates the T cell antigen receptor/CD3 complex but not the CD2 molecule and inhibits signaling via both receptor structures in the human T cell lymphoma Jurkat
Authors: Sommermeyer Henning , Schwinzer Reinhard , Kaever Volkhard , Wessel Klaus , Schmidt Reinhold E. , Behl Berthold , Wonigeit Kurt , Szamel Marta , Resch Klaus 
Published: March 2007

AbstractThe human T cell lymphoma Jurkat can be activated by stimuli directed either against the T cell antigen receptor‐CD3 antigen complex (TcR/CD3) or the CD2 molecule. Stimulation of cells via the TcR/CD3‐complex or via the CD2 molecule increases inositol phosphates and cytoplasmic free calcium. Pretreatment of Jurkat cells with cholera toxin leads to a decrease of TcR/CD3 expression on the surface of the cells, while the expression of CD2 is unaffected. In contrast to this distinct effect on the receptor expression, signaling via both pathways is inhibited by cholera toxin. The most convincing explanation for the cholera toxin‐mediated inhibition of signaling is that cholera toxin interrupts the signaling pathways at a point where both, stimulation via TcR/CD3 and via CD2, use the same route. The earliest common point of the two signaling pathways, at least in the Jurkat cell line, seems to be the CD3 complex because after its down‐regulation (and functional inactivation) both pathways of activation are interrupted.
Synergistic action of calcium ionophore A23187 and protein kinase C activator bryostatin 1 on human B cell activation and proliferation
Authors: Drexler Hans G. , Gignac Suzanne M. , Pettit George R. , Hoffbrand A. Victor 
Published: March 2007

AbstractIn this study we have examined the immunostimulatory effects of the macrocyclic lactone bryostatin 1 on various aspects of B cell activation and proliferation using human tonsillar B cells. Bryostatin 1 is an activator of protein kinase C (PKC) and its properties were compared to those of the classical PKC activator phorbol 12‐myristate 13‐acetate (PMA), a phorbol ester. Time‐course kinetics and dose‐response curves of RNA and DNA synthesis induced by bryostatin 1 or PMA were comparable, albeit the phorbol ester was significantly more potent. The responses triggered by both bryostatin 1 and PMA could be blocked by the PKC inhibitor H7. Bryostatin 1 and PMA mediated similar effects with regard to the activation parameters, increase in cell size, expression of activation‐associated antigens and hyperexpression of major histocompatibility complex class II antigens. Addition of the calcium ionophore A23187 to bryostatin 1‐treated cultures resulted in synergistically enhanced activation and proliferation responses, and this potentiation by A23187 could be inhibited by cyclosporin A. Bryostatin 1 antagonized the effects of PMA‐triggered stimulation in a time‐ and dose‐dependent manner. The basis for this modulation of PMA‐induced effects and the reason for the difference in the abilities of the two agents to stimulate B cells is unclear; possibly, bryostatin 1 and PMA activate different isoforms of PKC and elicit different signals on intracellular biochemical pathways.Bryostatin 1 lacks the tumor‐promoting activity of PMA and is a potent anti‐neoplastic substance. These features together with its immunomodulatory properties qualify bryostatin 1 as a candidate for in vivo use as a biological response modifier.
Differential activity of interleukin 1α and interleukin 1β in the stimulation of the immune response in vivo
Authors: Boraschi Diana , Villa Luigi , Volpini Gianfranco , Bossù Paola , Censini Stefano , Ghiara Paolo , Scapigliat Giuseppe , Nencioni Luciano , Bartalini Marcella , Matteucci Giacomo , Cioli Franca , Carnasciali Marzia , Olmastroni Enza , Mengozzi Manuela , Ghezzi Pietro , Tagliabue Aldo 
Published: March 2007

AbstractThe biological activities of human recombinant interleukin (IL) 1α and IL 1β were compared in different biological systems. The two IL 1 forms were equally active in vitro in inducing proliferation of murine thymocytes and of the murine T helper clone D10.G4.1, and in triggering release of prostaglandin E2 from human skin fibroblasts. In vivo, IL 1α and IL 1β were similarly pyrogenic both in rabbits and mice, and could equally increase the circulating levels of the acute phase protein serum amyloid A in mice. However, only IL 1β showed immunostimulatory activity in vivo, as it could enhance the number of specific antibody‐producing cells in the spleen of mice immunized with either a T‐dependent or a T‐independent antigen. Although devoid of immunostimulatory activity, IL 1α could efficiently compete immunostimulation induced by IL 1β, suggesting an effective interaction with the IL 1 receptor. Thus, IL 1β appears to have an important role in the positive regulation of immune responses, while IL 1α may act as down‐regulator of the IL 1β effect.
Purification and characterization of a 26‐kDa competitive inhibitor of interleukin 1
Authors: Mazzei Gonzalo J. , Seckinger Philippe L. , Dayer Jean‐Michel , Shaw Alan R. 
Published: March 2007

AbstractThe urine of patients with fever above 39 °C contains an inhibitor of interleukin 1. Herein we describe the purification of the interleukin 1 inhibitor by ion‐exchange chromatography, hydrophobic chromatography, gel filtration and negative immunosorption. The purified protein has a molecular weight of 26000; its size is reduced to 24000 upon treatment with endoglycosidase F. The IL 1 inhibitor is a competitive inhibitor and acts by binding to the IL 1 receptor. The inhibitor recognizes the murine and human IL 1 receptor with similar affinity. The purified IL 1 inhibitor has a specific activity of 3 × 107 to 4.5 × 107 units/mg as tested on the human astrocytoma (U‐373) cell proliferation bioassay and murine EL4.6.1 cell IL 1 receptor‐binding assay.
Lymphokines and bacteria, that induce tumoricidal activity, trigger a different secretory response in macrophages
Authors: Keller Robert , Keist Ruth , Frei Karl 
Published: March 2007

AbstractThe abilities of various macrophage‐activating agents to trigger tumoricidal activity and/or the secretion of prostaglandin E2 (PGE2), interleukin 6 (IL 6) and transforming growth factor β (TGFβ) in bone marrow‐derived mononuclear phagocytes (BMMΦ) in vitro were comparatively assessed. Induction of tumoricidal activity by lymphokines, that is only short‐lived, was not associated with enhanced secretion of these activities by BMMΦ; in contrast, incubation with heat‐killed facultative intracellular bacteria resulted in persisting tumoricidal activity and in marked enhancement of the secretion of IL 6 and PGE2, but not of TGFβ activity. These findings support the concept that the pattern of the secretory response induced in macrophages by lymphokines differs from that triggered by bacteria and that the rapid decay of lymphokine‐induced tumoricidal activity is not due to autocrine macrophage deactivation mediated by one of these agents alone.
CD4+CD8+ thymocytes are susceptible to DNA fragmentation induced by phorbol ester, calcium ionophore and anti‐CD3 antibody
Authors: Tadakuma Takushi , Kizaki Harutoshi , Odaka Chikako , Kubota Ryo , Ishimura Yuzuru , Yagita Hideo , Okumura Ko 
Published: March 2007

AbstractStimulation of murine thymocytes with phorbol ester or calcium ionophore for 18–24 h resulted in 70%–80% fragmentation of DNA into 180–200‐bp multiples, followed by cell death. Experiments with fractionated subpopulations by panning or flow cytometry revealed that DNA fragmentation was selectively observed in CD4+CD8+ cells and in a portion of CD4−CD8+ cells. To investigate whether DNA cleavage is also inducible via antigen‐specific receptors, thymocytes were incubated in wells precoated with anti‐CD3 antibody. An approximately 20% increase of DNA fragmentation was constantly observed when unseparated thymocytes were stimulated with anti‐CD3 antibody. In this anti‐CD3‐induced DNA degradation, CD4+CD8+ cells are probably the target cells, since (a) fetal thymocytes at day 18 of gestation were found vulnerable to anti‐CD3‐induced DNA cleavage and (b) flow cytometry analysis of viable cells recovered after cultivation in the anti‐CD3‐coated wells revealed that CD4+CD8+ cells were preferentially decreased. Further experiments with purified CD4+CD8+ cells, however, could not define a clear‐cut increase of DNA fragmentation when isolated CD4+CD8+ cells were stimulated with anti‐CD3 antibody. Addition of interleukin (IL) 1, IL 2, IL 3, IL 4 or interferon‐γ to the CD4+CD8+ cell cultures failed to yield a DNA cleavage similar to that of unseparated thymocytes.
T cell receptor gene rearrangements of T lymphocytes infiltrating the liver in chronic active hepatitis B and primary biliary cirrhosis (PBC): Oligoclonality of PBC‐derived T cell clones
Authors: Moebius Ulrich , Manns Michael , Hess Georg , Kober Gabriela , zum Büschenfelde Karl‐Herrmann Meyer , Meuer Stefan C. 
Published: March 2007

AbstractImmunological events are involved in the pathophysiology of chronic active hepatitis as indicated from the accumulation of T lymphocytes at the site of tissue damage. We generated T cell clones from liver biopsies of 3 patients with chronic active hepatitis B and 2 patients with primary biliary cirrhosis. These T cell clones (n = 84) were analyzed by means of T cell receptor (TcR) β gene rearrangements to determine whether the infiltrate consists of a polyclonal or oligoclonal T cell population. The vast majority (62 of 64) of T cell clones from three different patients with chronic active hepatitis B showed no identical rearrangements of the TcR β chain genes. In marked contrast, in both patients with primary biliary cirrhosis, T cell clones established were of limited diversity. Thus 5 out of 10 and 2 out of 10 T cell clones from one patient and 3 out of 9 and 2 out of 9 T cell clones from the second patient, respectively, showed identical TcR β gene rearrangements. These data suggest that a clonal dominance is characteristic for local T cell responses in autoimmune liver disease such as primary biliary cirrhosis whereas in virus‐induced chronic active hepatitis T cell activation occurs polyclonally.
Natural killer cells carry the germ‐line configuration of the T cell receptor δ chain gene and heterogeneously express six distinct δ transcripts
Authors: Carè Alessandra , Pelicci Pier G. , Meccia Ettore , Fagioli Marta , Testa Ugo , Ciccone Ermanno , Moretta Alessandro , Moretta Lorenzo , Peschle Cesare 
Published: March 2007

AbstractInvestigations on T cell receptor δ chain (TcR δ) gene expression in freshly isolated normal large granular lymphocytes, natural killer (NK) cell clones and NK bulk cultures revealed six Tδ transcripts (3.5, 3.1, 2.2, 2.0, 1.5 and 1.3 kb) which varied in number and relative abundance in the different samples. None of the six known Tδ variable regions was expressed and the Tδ locus was retained in its germ‐line configuration. The origin and significance of these NK‐associated Tδ transcripts are discussed.
Detection of intracellular expression and secretion of interferon‐γ at the single‐cell level after activation of human T cells with tetanus toxoid in vitro
Authors: Kabilan Lalitha , Andersson Gudrun , Lolli Francesco , Ekre Hans‐peter , Olsson Tomas , Troye‐blomberg Marita 
Published: March 2007

AbstractActivation of Tcells results in intracellular expression and secretion of cytokines such as interferon (IFN)‐γ. Here we have used three different assays for determination of IFN‐γ in tetanus toxoid‐ or mitogen‐activated human T cell cultures. Two of these assays [intracytoplasmic immunofluorescence and enzyme‐linked immuno spot assay (ELISPOT)] determined the expression and secretion of IFN‐γ at the single‐cell level while the third assay enzyme‐linked immunosorbent assay (ELISA) measured IFN‐γ secreted into the culture supernatant. Comparison of all three tests revealed a good correlation between the ELISPOT assay and the ELISA, whereas expression of intracellular IFN‐γ showed a qualitative but not a quantitative correlation with the latter. Both the immunospot assay and the immunofluorescence may be used to detect approximate numbers of specific T cells even when present at low frequencies. With the use of the immunospot assay antigen‐specific T cells could be detected even in the absence of detectable IFN‐γ in the culture supernatants. However, the ELISA assay should be more convenient for screening large clinical material.
Tumor necrosis factor‐α in combination with interferon‐γ, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes
Authors: Bogdan Christian , Moll Heidrun , Solbach Werner , Röllinghoff Martin 
Published: March 2007

AbstractWe have previously shown that during an infection with Leishmania major, susceptible BALB/c mice, as opposed to mice of a resistant strain (C57BL/6), are primed by lipopolysaccharide for the production of high levels of tumor necrosis factor‐α (TNF‐α) which is known to be a potent macrophage (MΦ) stimulator in other parasitic diseases. In the present study we investigated whether TNF‐α activates MΦ for killling of L. major parasites. In the absence of interferon‐γ (IFN‐γ) or lipopolysaccharide, TNF‐α (0.025—25000 U/ml) failed to activate peritoneal exudate MΦ from BALB/c micefor killling of L. major amastigotes. In the presence of suboptimal doses of IFN‐γ (5 or 10 U/ml), however, TNF‐α mediated a rapid elimination of intracellular parasites, which was highly significant compared to IFN‐γ alone. The combination of TNF with interleukin 4, in contrast, was inactive in this respect and allowed survival of intracellular parasites. From these data we conclude that thepresence of IFN‐γ is curcial for TNF‐α‐mediated killing of L. major parasites by MΦ. Disease progression in susceptible mice thereforeseems to be a consequence of a deficiency of IFN‐γ and a predominance of interleukin 4 rather than the result of an excess amount of TNF‐α.
Inhibition of interleukin 4 receptor expression on human lymphoid cells by cyclosporin
Authors: Foxwell Brian M. J. , Woerly Gaetane , Ryffel Bernhard 
Published: March 2007

AbstractThe effect of the immunosuppressant cyclosporin (CsA) on the expression of interleukin (IL) 4 membrane receptors on human peripheral blood mononuclear cells (PBMC) was investigated after cell activation by anti‐CD3 antibody, IL 2 or IL 4. Previous studies with 125I‐labeled IL 4 identified on resting lymphocytes a trimolecular complex consisting of a 65/70‐kDa doublet and a 110‐kDa protein with ∼︁ 300 high‐affinity binding sites (Kd 100 pM) and ∼︁ 9000 low‐affinity binding sites (Kd 30 nM). Upon cell activation by anti‐CD3 antibody both low‐ and high‐affinity binding sites increased about threefold concomitant with upregulation of all the cross‐linked proteins. CsA inhibited anti‐CD3 antibody‐induced up‐regulation of IL 4 receptor (IL 4R)‐associated proteins as well as the expression of high‐affinity binding sites. However, up‐regulation of IL 4R by its own ligand or IL 2 and the growth‐promoting effect of IL 4 on activated, IL 4R+ T cells were CsA resistant. Since CsA inhibits the synthesis of IL 4, exogenous IL 4 was added to the cultures and it partially reversed the inhibitory effect of CsA on cell proliferation as well as on IL 4R expression. It is concluded that the inhibitory effect of CsA on IL 4R expression may contribute to the immunosuppressive effect of the drug.
Dissociation of unidirectional influx of external Ca2+ and release frominternal stores in activated human T lymphocytes*
Authors: Gelfand Erwin W. , Cheung Roy K. 
Published: March 2007

AbstractAddition of lectin or antibody to the T cell receptor complex of human T cells results in a rapid increase in the concentration of cytoplasmic free Ca2+ ([Ca2+]i). This response is biphasic and results from contributions of Ca2+ from internal stores, uptake of Ca2+ across the plasma membrane and possibly a decrease in Ca2+ efflux. These responses have been linked through the activity of inositol 1,4,5‐trisphosphate in releasing Ca2+ from internal stores and potentially mediating Ca2+ uptakeacross the plasma membrane. Following addition of phytohemagglutinin or anti‐CD3 antibody to resting T cells or Jurkat cells, we have been able to dissociate the [Ca2+]i responses by loading cells with the Ca2+ chelator 1,2‐bis(Oaminophenoxy)ethaneN,N,N',N'‐tetraacetate (BAPTA). In BAPTA‐loaded T cells, we have shown that Ca2+ mobilized from intracellular stores following activation is effectively buffered, while stimulated Ca2+ uptake and associated changes in [Ca2+]i were relatively unaffected. In this report, we show that the sustained increase in [Ca2+]i is due to increased unidirectional influx of external Ca2+ without changes in efflux and that it is the entry of extracellular Ca2+ which is sensitive to the transmembrane potential.
Definition of the human immunoglobulin variable lambda (IGLV) gene subgroups
Authors: Chuchana Paul , Blancher Antoine , Brockly Frédérique , Alexandre Daniel , Lefranc Gérard , Lefranc Marie‐paule 
Published: March 2007

AbstractComparison of 60 human immunoglobulin variable lambda (IGLV) sequences allowed us to define seven subgroups designated VλI to VλVII. We demonstrate that all λ proteins sequenced so far fall into the subgroups I, II, III and VI, and that the λ regions previously assigned to subgroups IV and V belong, in fact, to subgroups III and II, respectively. Four sequences not belonging to any of the subgroups I, II, III and VI define the new subgroups IV, V and VII. Interestingly, these subgroups show a higher homology to rabbit or mouse Vλ genes than to the other human Vλ subgroups. By comparison of the proteins either with the sequences deduced from the germ‐line genes or with the consensus sequences, therate of amino acid changes due to somatic mutations or allelic variations was evaluated in several λ proteins. Framework and complementarity‐determining regions of the human IGLV genes and proteins were delineated. Alignment of the λ sequences shows that functional V‐J rearrangement occurs, with or without deletion of nucleotides encoding one or two amino acids at the 3′ end of the V gene. Diversity of the third complementarity‐determining region is due to somatic mutations and to flexibleV‐J junction, but there is no evidence of N‐diversity in the human λlocus.
T cell activation by a bispecific anti‐CD3/anti‐major histocompatibility complex class I antibody
Authors: Roosnek Eddy , Tunnacliffe Alan , Lanzavecchia Antonio 
Published: March 2007

AbstractA bispecific anti‐CD3/anti‐major histocompatibility complex (MHC) class I antibody (Ab) that is able to activate human T cells in the absence of a second signal has been used to compare activation by this Ab to signaling by anti‐CD3 Ab orby antigen (Ag). We have studied early, intermediate and late events that occur after triggering of a tetanus toxoid‐specific T cell clone. While bivalent anti‐CD3 Ab induce transient (<20 min) intracellular Ca2+ concentration increases, the bispecific Ab, like antigen‐presenting cells plus Ag, produces sustained (> 2 h) elevated intracellular Ca2+ concentration. In addition, while the anti‐CD3 Ab only induces low levels of c‐myc mRNA lasting less than 3 h, the bispecific Ab induces high levels which are maintained for at least 8 h after triggering. Late events, such as interleukin 2 receptor expression and proliferation, occurring more than 20 h after activation, were seen only when T cells were stimulated by bispecific Ab or by antigen‐presenting cell and Ag. Cells activated by linking T cell receptor(TcR)/CD3 to MHC class I antigens could not be activated by cross‐linking the MHC and TcR/CD3 structures separately. Therefore, we propose that the bispecific Ab functions by modifying the membrane dynamics of the TcR/CD3 complex, rather than by the generation of a second signal through class I antigens.
Characterization of the CD3 γ and δ invariant subunits of the sheep T cell antigen receptor
Authors: Hein Wayne R. , Tunnacliffe Alan 
Published: March 2007

AbstractThe CD3 γ and δ chains of the sheep T cell antigen receptor have been characterized by cDNA cloning. In comparison to human and mouse protein sequences, short oligopeptide stretches have been deleted from both the γ and δ chains. However, apart from further variability in the number and position of potential N‐linked glycosylation sites, the general structure of the CD3 γ and δ proteins is markedly conserved. Particularly remarkable are two motifs consisting of 8 and 32 amino acids, respectively, which locate in the C‐terminal half of each protein and which have been precisely conserved in both the CD3 γ and δ chains of all three species. These motifs probably contribute structural properties essential for the function of the CD3/T cell receptor complex. mRNA of the sheep CD3 γ (1.5 and 1.2 kb) and CD3 δ (1.5 kb) chains are transcribed from closely linked, single‐copy genes, suggesting that common mechanisms for the regulation of CD3 genes are also preserved between species.