bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of anti‐GD3‐ganglioside antibody‐induced proliferation of human CD8+ T cells by CD16+ natural killer cells
Authors: Claus Christine , Schlaak Jörg , Dittmayer Maria , Zum Karl‐Hermann Meyer , Büschenfelde  , Dippold Wolfgang 
Published: March 2007

AbstractThe ganglioside GD3 has been described as a membrane component of human T cells which is involved in T cell growth. In the present study the activating function of GD3 for human CD4+ and CD8+ T cells was analyzed by five different monoclonal antibodies (mAb) directed against the GD3 molecule. Three mAb U5, Z21 and R24 induced strong proliferation of peripheral blood mononuclear cells and purified CD8+ and CD4+ T cells of normal donors containing less than 5% CD16+ natural killer (NK) cells. In contrast to CD4+ T cells, CD8+ T cells proliferated only weakly in the presence of 15% CD16+ NK cells. The proliferative response of purified CD4+ and CD8+ T cells (<5% NK cells) correlated with the antibody‐dependent induction of integral and soluble interleukin‐2 (IL‐2) receptors and was reduced to 20% by an anti‐IL‐2 receptor antibody. Our results show, that the GD3 molecule represents an activation molecule for both CD4+ and CD8+ T cells and that CD16+ NK cells selectively inhibit anti‐GD3 antibody‐induced proliferation of CD8+ T cells.
CD38 signaling by agonistic monoclonal antibody prevents apoptosis of human germinal center B cells
Authors: Zupo Simona , Rugari Emanuela , Dono Mariella , Taborelli Giuseppe , Malavasi Fabio , Ferrarini Manlio 
Published: March 2007

AbstractThe present study demonstrates that an agonistic anti‐CD38 monoclonal antibody (mAb) (IB4) is capable of preventing apoptosis of human tonsillar germinal center (GC) B cells as measured by either morphological methods on Giemsa‐stained cytospin preparations or flow cytometry on propidium iodidestained cells. Two other anti‐CD38 mAb (Leu‐17 and OKT10) consistently failed to prevent apoptosis in the same cells, even when tested over a wide range of concentrations. Furthermore, exposure of GC B cells to IB4 mAb up‐regulates the bcl‐2 proto‐oncogene product in a manner similar to that observed with CD40 ligand (CD40L). The ability of IB4 mAb to prevent apoptosis of GC B cells was inferior to that of both anti‐CD40 mAb and CD40L. No synergistic or additive effects were observed when IB4 mAb was used together with CD40L. Unlike anti‐CD40 mAb or CD40L, IB4 mAb neither induced a proliferation of GC B cells nor increased their proliferative response to anti‐CD40, CD40L or recombinant interleukin‐4, used alone or in combination. The present results are consistent with the recent findings on either the feature of the CD38 molecules to deliver activation signals and on the mechanisms of selection of B cells that operates in the GC.
Processing of viable group A streptococci leads to major histocompatibility complex class II presentation of T cell epitopes from the major protective antigen
Authors: Rossiter Beth A. , Alfonso Christopher , Kehoe Michael A. , Robinson John H. 
Published: March 2007

AbstractWe have previously mapped major histocompatibility complex (MHC) class II‐restricted T cell epitopes of the surface M protein of type 5 group A streptococci (M5) and show here that two out of four epitopes investigated were efficiently processed during incubation of viable streptococci with spleen cells for presentation to M5‐specific murine T cell clones. Viable streptococci were processed more efficiently than heat‐killed bacteria suggesting that secreted virulence factors of streptococci do not obstruct processing of streptococcal antigens in the dose range used. Epitopes from different regions of M5 could be ranked according to the efficiency with which they were processed, which may contribute to their relative immunodominance. It was further demonstrated that T cell clones specific for M5 308–319, an epitope from the M type conserved carboxy‐terminal half of M5, cross‐reacted between M5, M6 and M12, but not M49, streptococci. Helper T cell epitopes which are shared between streptococcal M types and are presented by MHC class II molecules on antigen‐presenting cells after processing of viable streptococci could be particularly useful in the design of multivalent streptococcal vaccines.
Comparing macrophages and dendritic leukocytes as antigen‐presenting cells for humoral responses in vivo by antigen targeting
Authors: Berg Siri Fuglem , Mjaaland Siri , Fossum Sigbjørn 
Published: March 2007

AbstractImmunotargeting is a novel technique whereby antigen is directed against antigen‐presenting cells (APC) by conjugation to specific monoclonal antibodies (mAb). In this study we have employed the technique to investigate the efficiency of macrophages as APC compared with constitutively major histocompatibility complex (MHC) class II‐positive cells. i.e. dendritic leukocytes and B cells. in vivo. We first studied the organ retention of the radiolabeled conjugates by gamma counting, and their distribution within the draining lymph nodes by autoradiography. We could confirm that the conjugates reached the cells at which they were aimed. We then measured primary and secondary humoral responses. The results confirmed previous findings that targeting with mAb against MHC class II, i.e. to dendritic leukocytes, strongly enhanced the primary humoral response. In contrast, anti‐IgD conjugates, directed against B cells gave only weak primary responses. Although conjugates directed against macrophages were retained for a longer time than the other conjugates, the primary humoral response was virtually abolished. The secondary responses, however, were at least as strong as those obtained in animals primed with control conjugates, whereas animals primed with anti‐MHC class II conjugates showed little if any amplification of the secondary response. The discrepancies between the various conjugates could not be ascribed to TH1 versus TH2 responses as IgG1, IgG2a, IgG2b and IgE titers all co‐varied in single animals. A possible explanation for the observed results is that macrophages fail to induce cytokine production for terminal differentiation of B cells to plasma cells, whereas conversely, upon presentation by dendritic leukocytes most stimulated B cells mature to plasma cells, leaving less progeny for immunological memory.
Multiple natural killer cell‐activating signals are inhibited by major histocompatibility complex class I expression in target cells
Authors: Correa Isabel , Corral Laura , Raulet David H. 
Published: March 2007

AbstractSeveral lines of evidence indicate that major histocompatibility complex class I molecules expressed by target cells can prevent natural killer cell (NK) lysis, possibly by engaging inhibitory receptors expressed by NK cells. On the other hand it is likely that NK cells must be activated to lysis by the recognition of unidentified NK target structures on target cells. To investigate the relationship between positive activation of NK cells by NK target structures versus inhibition by target cell class I molecules, we have examined various NK/target cell interactions for which the expression of inhibitory class I molecules by the target cells is known. The results suggest that specific properties of the target cell other than the absence of class I expression are necessary to activate NK‐mediated lysis. Furthermore, different effector cell populations, i.e. freshly isolated versus interleukin‐2 activated NK cells, differ in their capacity to kill class I‐deficient lymphoblast target cells. In general, class I‐deficient target cells that are resistant to direct lysis by a given NK population can be lysed by the NK cells when the reaction is mediated by antibody‐dependent cellular cytotoxicity (ADCC). Most significantly, all types of NK‐mediated lysis of lymphoblasts, of tumor cells and of almost any target by ADCC can be inhibited by appropriate class I gene expression in the target cell. These results suggest a model in which lysis by NK cells must be triggered by any one of a set of distinct target cell ligands, but that all of these signals can be overruled by class I‐mediated inhibition.
Characterization of brain‐isolated rat encephalitogenic T cell lines
Authors: Sun Deming , Hu Xian‐Zheng , Le Junyi , Swanborg Robert H. 
Published: March 2007

AbstractIn the present study, we have isolated and characterized five myelin basic protein (MBP)‐reactive T cell lines directly from the brains of Lewis rats during the early paralytic phase of experimental autoimmune encephalomyelitis (EAE). Each T cell line responded to the dominant encephalitogenic epitope spanning residues 68–88, and did not react against the conserved encephalitogenic epitope [MBP(87–99)] or the nonencephalitogenic MBP epitope [MBP(50–69)]. We determined the T cell receptor (TcR) β chain usage by polymerase chain reaction, DNA sequencing analysis and by generation of MBP‐reactive hybridomas from one of the T cell lines (BT74). The results revealed that brain‐infiltrating, MBP‐reactive T cells freshly isolated early in the course of the disease exhibit TcR diversity.
Signaling through CD50 (ICAM‐3) stimulates T lymphocyte binding to human umbilical vein endothelial cells and extracellular matrix proteins via an increase in β1 and β2 integrin function
Authors: Cid Maria C. , Esparza Jordi , Juan Manel , Miralles Agust́i , Ordi Jaume , Vilella Ramón , Urbano‐Márquez Alvaro , Gayà Antoni , Vives Jordi , Yagüe Jordi 
Published: March 2007

AbstractRegulated adhesion of T lymphocytes to antigen‐presenting cells, endothelial cells and extracellular matrix proteins is crucial in T lymphocyte activation and migration to the sites of injury. In this study, we show that three monoclonal antibodies (mAb) recognizing different epitopes on the CD50 (ICAM‐3) molecule increase T lymphocyte adhesion to tumor necrosis factor (TNF)‐stimulated human umbilical vein endothelial cells and extracellular matrix proteins. These phenomena are mediated by an increase in β1 and β2 integrin avidity since (a) CD50‐induced adhesion to endothelial cells was abrogated by simultaneous blocking of β1‐ and β2‐mediated adhesion pathways but not by interfering with either one individually, (b) CD50 mAb increased β1 integrin‐mediated adhesion to extracellular matrix proteins and to fibronectin‐derived synthetic peptides, (c) CD50 mAb enhanced T lymphocyte binding to ICAM‐1 transfectants, and (d) CD50 mAb did not modify surface expression patterns of β1 or β2 integrins on T lymphocytes. Our data suggest that constitutively expressed CD50 (ICAM‐3) can play a pivotal role in initiating a cascade of adhesion events which may be crucial in immune activation and in the development of inflammatory lesions.
Suppression of polyclonal and antigen‐specific murine IgG1 but not IgE responses by neutralizing interleukin‐6 in vivo
Authors: Van Ommen René , Vredendaal Astrid E. C. M. , Savelkoul Huub F. J. 
Published: March 2007

AbstractThe crucial role of interleukin (IL)‐4 in the induction of murine IgG1 and IgE responses, which are coupled through the process of sequential isotype switching, has been well documented. Whereas IL‐4 is obligatory for the induction of IgE responses, it enhances IgG1 responses. In this study, using neutralizing antibodies, we provide evidence that, besides IL‐4, also IL‐6 is required for obtaining peak IgG1 responses. The mRNA levels of these two cytokines are coordinately expressed in the spleen of mice immunized with trinitrophenol‐keyhole limpet hemocyanin (TNP‐KLH). No IL‐6 requirement was observed for peak IgE responses. The IL‐6 dependence of IgG1 responses was found for both antigenspecific and polyclonal responses. Moreover, it was noted using TNP‐KLH and goat anti‐mouse (GAM) IgD as antigen that polyclonal IgG1 responses are more dependent on IL‐6 than antigen‐specific responses. In vitro experiments revealed that exogenous IL‐6 neither enhanced nor inhibited the IgG1 and IgE production by naive B cells, suggesting that IL‐6 did not interfere with the IL‐4‐induced isotype switch potential. Primary and memory IgG1 responses were both similarly dependent on IL‐6. These observations point to a role of IL‐6 in the terminal differentation of B cells switched to IgG1. Neutralization of IL‐6 did not inhibit either antigen‐specific or polyclonal IgE responses. Therefore, it was concluded that IL‐6 is not involved in the terminal differentiation of B cells switched to IgE. These findings thus provide a distinct role for IL‐6, besides IL‐4, in regulating murine IgG1 responses. The formation of IgE, however, is completely dependent on IL‐4 alone.
Induction of anergy in resting human T lymphocytes by immobilized anti‐CD3 antibodies
Authors: Wolf Hans , Müller Yvonne , Salmen Sibylle , Wilmanns Wolfgang , Jung Gundram 
Published: March 2007

AbstractHow the T cell receptor (TcR)/CD3 complex mediates not only the induction of T cell activation but also suppressive effects like T cell anergy or apoptosis is not well understood. Here we describe a series of preincubation and restimulation experiments which demonstrate that primary stimulation of resting, unseparated human T cells with mitogenic doses of immobilized anti‐CD3 antibodies induces hyporesponsiveness upon restimulation of the cells. Various costimuli can prevent this type of anergy to a variable degree if present during the preincubation period, phorbol 12‐myristate 13‐acetate (PMA) being the most and anti‐CD4 antibody the least effective. If employed together with anti‐CD3 antibody during the restimulation phase of the assay, interleukin (IL)‐2, IL‐4 and anti‐CD28 antibody break anergy almost completely. Proliferation induced by a submitogenic dose of anti‐CD3 antibody supplemented by costimulatory signals (anti‐CD2, anti‐CD4, anti‐CD28, IL‐2, IL‐4 or PMA) does not result in hyporesponsiveness. Taken together, these results support a modified view of the two‐signal model for T cell activation according to which anergy induction in resting T cells occurs if primary proliferation is induced by high density triggering of the TcR/CD3 complex in the absence of accessory signals. We discuss possible implications of these findings for the induction of peripheral tolerance.
Natural amino acid polymorphisms of the circumsporozoite protein of Plasmodium falciparum abrogate specific human CD4+ T cell responsiveness
Authors: Zevering Yinka , Khamboonruang Chirasak , Good Michael F. 
Published: March 2007

AbstractSequence polymorphism has been reported for virtually all malaria antigens and, in the case of the circumsporozoite (CS) protein, this variation is in the form of point mutations concentrated primarily in several regions recognized by T cells. The factors responsible for the variation are unknown. We studied the T cell responses to all known variants in malaria‐exposed Thais. Memory CD4+ T cells responded to variants of a polymorphic immunodominant region (denoted Th2R), and CD4+ T cell clones specific for one Thai Th2R variant were generated. There was minimal cross‐reactivity to any of the naturally occurring variants, including the other Thai variant, and competition studies performed with the clones using analog peptides demonstrated that all the substitutions of the polymorphic residues modulate either the binding of the peptide to major histocompatibility complex (MHC) molecules or the recognition by the T cell receptor of the peptide‐MHC complex. Our data suggest that CD4+ T cells may be able to select parasites expressing variant sequences and have implications for development of a CS‐based vaccine.
Interleukin‐10 prevents experimental allergic encephalomyelitis in rats
Authors: Rott Ortwin , Fleischer Bernhard , Cash Evelyne 
Published: March 2007

AbstractExperimental allergic encephalomyelitis (EAE) is an autoimmune disease mediated by myelin protein‐specific CD4+ T lymphocytes of the Th1‐like phenotype. In rats, the disease is characterized by a monophasic clinical manifestation, followed by a subsequent spontaneous remission and the establishment of life‐long resistance to reinduction of disease. Recent data indicate that intracerebral cytokine production, in particular synthesis of interleukin(IL)‐10, is selectively up‐regulated during the recovery phase of disease. This led us to assess the effects of IL‐10 on different rat lymphoid cell functions in vitro and to consider the possibility of an IL‐10‐mediated treatment to prevent the induction of central nervous system (CNS) autoimmune disease in vivo. Human recombinant IL‐10 suppressed interferon‐γ induced major histocompatibility complex class II up‐regulation in rat peritoneal macrophages, exhibited pleiotropic effects on thymocytes and totally abrogated tumor necrosis factor production of encephalitogenic T lymphocytes in vitro, without simultaneously affecting proliferative responses of the cells. Upon systemic administration during the initiation phase of disease, IL‐10 was effective in markedly suppressing the subsequent induction of EAE in Lewis rats. This suppression of clinical disease coincided with a significant and specific elevation of myelin basic protein‐specific autoantibody production, a sustained T cell proliferative response to myelin basic protein and a diminution of CNS infiltrations and thymic involutions in diseased animals. These data implicate IL‐10 as a possible candidate for treatment of Th1‐mediated CNS (auto‐) immune diseases.
Use of a skin test assay to determine tumor‐specific CD8+ T cell reactivity
Authors: Puccetti Paolo , Bianchi Roberta , Fioretti Maria C. , Ayroldi Emira , Uyttenhove Catherine , van Pel Aline , Boon Thierry , Grohmann Ursula 
Published: March 2007

AbstractWe have observed delayed‐type hypersensitivity (DTH) reactions in immunized mice challenged subcutaneously with class I‐binding peptides related to rejection antigens recognized by cytotoxic T lymphocytes on mutagenized (tum−) variants of mastocytoma P815. As observed by skin test in virally infected mice challenged with viral peptides, the intrafootpad injection of tum− peptides resulted in a dose‐dependent DTH that peaked at approximately 24 h. The response was mediated by CD8+ cells and could be induced by previous vaccination of mice with live tumor cells, intrasplenic deposition of the eliciting peptide, or adoptive transfer with peptide‐pulsed syngeneic dendritic cells. These sensitization procedures resulted in an immunologically specific footpad reaction detectable for up to 2–6 months after priming. The evaluation by DTH in cancer patients of long‐lived CD8+ anti‐tumor T cell responses following local challenge with tumor‐specific peptides may be of great interest in human immunotherapy trials involving immunization against identified tumor antigens.
A role for CD4+ T cells in the pathogenesis of skin fibrosis in tight skin mice
Authors: Wallace Valerie A. , Kondo Seiji , Kono Takeshi , Xing Zhou , Timms Emma , Furlonger Caren , Keystone Edward , Gauldie Jack , Sauder Daniel N. , Mak Tak W. , Paige Christopher J. 
Published: March 2007

AbstractThe tight skin (Tsk/+) mouse represents a murine model of heritable fibrosis with some similarities to the skin fibrosis seen in human scleroderma. Tsk/+ animals display alterations in connective tissue in some internal organs. Skin fibrosis can be adoptively transferred to normal recipients with Tsk/+ bone marrow or spleen cells and older Tsk/+ animals develop autoantibodies against topoisomerase suggesting that some of the pathogenesis in the Tsk/+ mouse may be mediated by autoimmunity. To determine the role of T cell subsets in the pathogenesis of fibrotic disease, Tsk/+ mice were bred with CD4‐ and CD8‐deficient (CD4−/− and CD8−/−) mice. Tsk/+ CD4−/− mice showed a marked reduction in skin fibrosis as well as decreased cellularity and only mild collagen disorganization as compared to Tsk/+ CD4+ CD8+ control mice yet did not differ from Tsk controls in the level of serum anti‐topoisomerase activity. In contrast, Tsk/+ CD8−/− mice exhibited the same histology in the skin as Tsk/+ controls yet had significantly reduced levels of serum anti‐topoisomerase activity. Lung pathology, i.e. emphysema, was unaffected by both the CD4 or CD8 mutations. These data show that only some of the pathological effects of the Tsk mutation are T cell dependent and that different T cell subsets affect different parameters in this multi‐organ model of fibrotic disease.
Presentation of Listeria monocytogenes antigens by major histocompatibility complex class I molecules to CD8 cytotoxic T lymphocytes independent of listeriolysin secretion and virulence
Authors: Szalay Gudrun , Hess Jürgen , Kaufmann Stefan H. E. 
Published: March 2007

AbstractVirulence and intracellular persistence of Listeria monocytogenes markedly depend on secretion of listeriolysin (Hly), which promotes invasion of the pathogen from the endosome into the cytosol. Recent studies have provided compelling evidence that Hly also facilitates recognition of listerial antigens, in association with major histocompatibility complex (MHC) class I molecules, by CD8 T lymphocytes. Data presented here confirm that the Hly‐deficient strains, the prfA− mutant L. monocytogenes SLCC53 and the transposon mutants L. monocytogenes M3 and M20 are avirulent for mice, and unable to replicate inside bone marrow‐derived macrophages (BMMΦ). Furthermore, BMMΦ infected with M3, M20 or SLCC53 were as efficiently lysed as BMMΦ infected with the Hly‐positive wild‐type strain EGD by MHC class I‐dependent CD8 cytotoxic T lymphocytes. Using the highly sensitive polymerase chain reaction method, hly mRNA was detectable in BMMΦ infected with L. monocytogenes EGD or SLCC53, but totally absent in M3‐infected BMMΦ. In the case of M20, an excision of the transposon occurred, but the excision was not precise and the hly gene was approximately 400 base pairs shorter. These findings argue against a unique role for Hly in MHC class I presentation of listerial antigens, although Hly appears central to virulence and intracellular replication. Thus, virulence of L. monocytogenes is dissociable from MHC class I presentation of listerial antigens.
CD57+ T lymphocytes are derived from CD57− precursors by differentiation occurring in late immune responses
Authors: d'Angeac Arnaud Dupuy , Monier Serge , Pilling Darrell , Travaglio‐Encinoza Adolfo , Rème Thierry , Salmon Mike 
Published: March 2007

AbstractCD3+ T cells expressing the 110‐kDa CD57 antigen are found in survivors of renal, cardiac and bone marrow transplants, in patients with acquired immune deficiency syndrome and in patients with rheumatoid arthritis. They are also present in normal individuals and expand upon ageing. They do not grow in culture and their role in the immune response is poorly understood. The expression of the various isoforms of the leukocyte common antigen (CD45) identifies a spectrum of differentiation in CD4+ and CD8+ T cells ranging from naive (CD45RA+CD45RBbrightCD45RO−) through early primed cells (CD45RA−RBbrightROdull) to highly differentiated memory cells which are CD45RA−RBdullRObright. CD45 isoforms expressed by CD57+ T cells showed distinct differences between CD4+ and CD8+ populations, but in each case indicated an advanced state of differentiation. The expression of T cell receptor Vβ families was highly variable between individuals, but both CD57+ and CD57− cells show a full range of the specificities tested. Vβ expression was more closely related within either the CD4+ or the CD8+ subsets, irrespective of CD57 expression, than between these subsets, suggesting a relationship between CD57+ and CD57− cells within the same T cell pool. This possibility was supported by experiments showing that CD3+CD57+ lymphocytes were similar to CD3+CD57− T cells in terms of the production of basic T cell cytokines [interleukin (IL)‐2, IL‐4, and interferon‐γ]. Furthermore, in vitro stimulation of CD3+CD57− T cells in secondary mixed leukocyte reaction or by co‐culture with IL‐2 and IL‐4 induced the appearance of CD3+CD57+ cells with phenotypic and functional similarities to in vivo CD3+CD57+ cells. These data strongly suggest that the expression of CD57 is a differentiation event which occurs on CD57− T cells late in the immune response.