bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenesis of the toxic shock syndrome: T cell mediated lethal shock caused by the superantigen TSST‐1
Authors: Miethke Thomas , Duschek Katja , Wahl Claudia , And Klaus Heeg , Wagner Hermann 
Published: March 2007

AbstractThe pathogenesis of the toxic shock syndrome (TSS) is only incompletely understood. We now present evidence that TSS toxin‐1 (TSST‐1), one of the superantigens produced by Staphylococcus aureus, induces lethal shock in D‐galactosamine sensitized mice. In this model TSS is dependent on T cells, since cyclosporin A (CsA) completely blocked development of shock, and since T cell‐deficient SCID mice did not show signs of disease upon injection with TSST‐1. However, SCID mice repopulated with T cells succumbed to lethal shock. The disease is characterized by a burst of lymphokines like interleukin‐2 (IL‐2) and tumor necrosis factor (TNF) released into the sera of TSST‐1‐treated animals. Already 1–2 h after TSST‐1 application TNF serum levels peaked and IL‐2 levels peaked around 4 h after treatment. TNF appears as key mediator of TSS, because anti‐TNF monoclonal antibodies protected TSST‐1‐challenged mice. Interestingly, the burst of TNF in serum was noted well in advance of detectable markers of T cell activation. Thus, about 5 % of all peripheral T cells started to express the IL‐2 receptors as late as 4 h after treatment. Comparing TSST‐1‐ and endotoxin‐induced shock we conclude that TNF effects shock in both diseases. However, the type of cells involved appears distinct in that T cells cause TSS triggered by the exotosin TSST‐1 while macrophages mediate the shock induced by endotoxins.
Suppression of B cell differentiation by ligation of membrane‐bound IgM
Authors: Grandien Alf , Modigliani Yves , Coutinho Antonio , Andersson Jan 
Published: March 2007

AbstractUsing B cells from the transgenic mouse line B6‐Sp6 and control littermates, stimulated by lipopolysaccharide (LPS) under novel culture conditions that provide for the response of all B cells, we show here that specific ligation of the surface IgM molecules always results in inhibition of terminal differentiation and immunoglobulin secretion by activated cells, regardless of the ligand. Thus, monoclonal antibodies to (a) the CH region of Ig (anti‐μ. and anti‐allotype), (b) the Cx region, (c) the V region (anti‐idiotype) of surface IgM, as well as (d) multivalent antigen (2,4,6‐trinitrophenyl‐bovine serum albumin), all show similar effects and dose‐response curves. IgD‐negative transgenic B cells are equally sensitive to IgM ligation‐dependent inhibition, as control (IgD‐positive) B cells. The allotype specificity of this inhibition, assessed by using anti‐u, allotype reagents to inhibit and assay the responses, suggests that B cells expressing transgenic or endogenous IgM in transgenic B6‐Sp6 mice are largely independent populations. These observations establish that anti‐IgM antibodies in conjunction with appropriate LPS stimulation, provide a universal model system for functional characterization of B cell responses.
Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen‐specific T cells
Authors: Moll Heidrun , Fuchs Harald , Blank Christine , Röllinghoff Martin 
Published: March 2007

AbstractMurine epidermal Langerhans cells (LC) have been shown to internalize Leishmania major, a cause of human cutaneous leishmaniasis, and to stimulate a vigorous parasite‐specific T cell response. The present study emphasizes the critical role of LC in leishmaniasis by documenting directly that LC have the ability to transport L. major from the skin to the draining lymph node (LN). This was revealed by irreversible labeling of LC with a fluorescent cell linker and in vivo tracking. In contrast, no migration to the LN was seen with L. major‐infected macrophages. These findings were consistent with the results of mixed labeling immunohistology showing that early in infection the expression of parasite antigen in the LN draining the lesion was confined to dendritic cells and could not be detected in macrophages. Furthermore, dendritic cells in LN draining the site of cutaneous infection stimulated L. mayor‐primed T cells in vitro and, most notably, were able to activate unprimed T cells capable of mediating parasite‐specific delayed‐type hypersensitivity reactivity in vivo. Taken together, the results indicate that LC capture L. major in the skin and transport it to the regional LN for initiation of the specific T cell immune response.
The mucosal T cell integrin αM290β7 recognizes a ligand on mucosal epithelial cell lines
Authors: Roberts Kevan , Kilshaw Peter J. 
Published: March 2007

AbstractThe integrin αM290β7 is expressed at high levels on mucosal T cells, particularly on those within the epithelium of the gut. We now report that a mouse T cell hybridoma, MTC‐1, with similar surface expression of this molecule, adhered strongly to cells of the mouse rectal carcinoma line CMT93 and that adhesion was blocked completely by the monoclonal antibody (mAb) M290. Other mAb to the αM290 or β7 subunits had little or no inhibitory effect. M290 also inhibited adhesion of the hybridoma to cells of the mouse lung carcinomas CTM64/61 and KLN205 but had little or no effect on adhesion to seven other mouse epithelial cell lines or to the human colon carcinoma line, HT29. Intraepithelial lymphocytes (IEL) isolated from the small intestine of BALB/c mice displayed potent Tcell receptor‐dependent cytotoxic effector function against CMT93 in the presence of low concentrations of Phytolacca americana lectin. This cytotoxic activity also was inhibited by the M290 mAb. Treatment of CMT93 cells with tumor necrosis factor‐a and interferon‐γ induced expression de novo of ICAM‐1 and reduced the inhibitory effect of M290 in tests both for adhesion and cytotoxicity. In further experiments cytotoxic activity of IEL against the mastocytoma P815 was investigated. This target cell was considered not to possess a ligand for the integrin. In this case cytotoxic effector function was triggered by anti‐CD3 mAb and, in contrast to results with CMT93, target cell lysis was increased in the presence of M290 and other antibodies to the integrin, suggesting a co‐stimulatory effect. These results show that αM290β7 recognizes a ligand on the surface of certain epithelial cell lines. Further, they provide the first clear indication that this integrin may play an important role in functional interactions between T cells and the mucosal epithelium.
Environmental modulation of the autonomy of cytotoxic T lymphocytes
Authors: Bodmer Helen , Obert Georges , Chan Susan , Benoist Christophe , Mathis Diane 
Published: March 2007

AbstractThe extent to which one compartment of the immune system depends on another for efficient function is important to establish to fully comprehend disease phenotypes arising from selective immunodeficiency. Just how much the major histocompatibility complex class I‐restricted cytotoxic T cell responses depend on class II‐restricted T cell help has been controversial. Using the influenza A virus system, we show that mice unable to make class II‐restricted T cell responses due to an engineered defect in class II molecule expression are able to mount virtually normal cytotoxic responses when bred under specific‐pathogen‐free conditions. However, when exposed to the more diverse environmental challenges of a conventional breeding facility, a situation that more closely parallels immuno‐deficient states in man, they show impaired cytotoxic responses.
Idiotypic cascade in the human high molecular weight melanoma‐associated antigen system: Fine specificity and idiotypic profile of anti‐anti‐idiotypic monoclonal antibodies
Authors: Yang Hong , Chen Zhi Jian , Kageshita Toshiro , Yamada Masanobu , Ferrone Soldano 
Published: March 2007

AbstractThe mouse anti‐idiotypic (anti‐id) monoclonal antibody (mAb) MK2–23 bears the internal image of the determinant defined by the syngeneic immunizing anti‐human high molecular weight melanoma‐associated antigen (HMW‐MAA) mAb 763.74, since it induces anti‐HMW‐MAA antibodies in syngeneic and xenogeneic hosts. To dissect the humoral immune response induced by mAb MK2–23 at the clonal level, 1351 hybridomas were generated from a BALB/c mouse immunized with mAb MK2–23. Serological and immunochemical assays showed that the anti‐anti‐idiotypic (anti‐anti‐id) mAb GH827, GH1002 and GH1081 react only with the immunizing anti‐id mAb MK2–23 and that the anti‐anti‐id mAb GH149, GH368, GH464, GH518, GH586, GH704, GH786 and GH1151 react with both mAb MK2–23 and HMW‐MAA. The eight HMW‐MAA binding anti‐anti‐id mAb resembled mAb 763.74 in their reactivity patterns with a panel of cell lines, although the extent of reactivity was lower. Staining of surgically removed melanoma lesions detected subtle differences in the reactivity patterns of the eight HMW‐MAA binding anti‐anti‐id mAb. This finding in conjunction with the differential ability of the eight anti‐anti‐id mAb to inhibit the binding of anti‐HMW‐MAA mAb 763.74 to melanoma cells and to mAb MK2–23 and with the different avidity of the binding to mAb MK2–23 suggest diversity in the fine specificity of the eight HMW‐MAA binding anti‐anti‐id mAb. Like mAb 763.74, the eight HMW‐MAA binding anti‐anti‐id mAb express the idiotopes recognized by the anti‐id mAb MK2–23 and MK2‐120. In contrast, the three anti‐anti‐id mAb GH827, GH1002 and GH1081, which do not bind HMW‐MAA binding anti‐anti‐id mAb to the antibodies elicited by the membrane‐bound HMW‐MAA corroborates the validity of the use of anti‐id mAb MK2‐23 as an immunogen to implement active specific immunotherapy in patients with malignant melanoma.
Pre‐exposure of murine macrophages to lipopolysaccharide inhibits the induction of nitric oxide synthase and reduces leishmanicidal activity
Authors: Severn Alison , Xu Damo , Doyle Jacqueline , Leal Ludmila M. C. , O'Donnell Catherine A. , Brett Sara J. , Moss David W. , Liew Foo Y. 
Published: March 2007

AbstractMurine macrophages produce nitric oxide (NO) from L‐arginine on stimulation with lipopolysaccharide (LPS), alone or with interferon‐γ (IFN‐γ). The effect of incubation of macrophages with low concentrations of LPS on NO synthesis on subsequent stimulation was investigated, using a murine macrophage cell line, J774, and peritoneal macrophages from CBA mice. Cells which had been incubated with LPS produced significantly lower amounts of NO, and expressed lower levels of NO synthase activity, following stimulation with IFN‐γ and LPS, or with a high concentration of LPS. This effect was not reversed by tumor necrosis factor‐α. The ability of CBA macrophages to kill the intracellular parasite Leishmania major was markedly reduced by pre‐incubation with LPS. Reduced NO production by macrophages previously exposed to LPS is a manifestation of endotoxin tolerance, and may represent an important means of regulation of NO synthesis and thus a survival mechanism for intracellular parasites.
Induction of virus‐specific cytotoxic T lymphocytes in vivo by liposome‐entrapped mRNA
Authors: Martinon Frédéric , Krishnan Sivadasan , Lenzen Gerlinde , Magné Rémy , Gomard Elisabeth , Guillet Jean‐Gérard , Lévy Jean‐Paul , Meulien Pierre 
Published: March 2007

AbstractThe induction of anti‐influenza cytotoxic T lymphocytes (CTL) in vivo by immunizing mice with liposomes containing messenger RNA (mRNA) encoding the influenza virus nucleoprotein (NP) is described. NP mRNA, obtained by in vitro transcription, was encapsulated into simple cholesterol/phosphatidylcholine/phosphatidylserine liposomes by the detergent removal technique. The dependance of the route of mRNA‐liposomes delivery on CTL induction was studied. The CTL induced were identical to those obtained in vivo with infectious virus in terms of specificity, lysing both peptide‐sensitized and virus‐infected targets. Furthermore, with the same mRNA‐liposome preparation, virus‐specific CTL responses could be also elicited in mice of three different haplotypes each of them known to present a distinct NP peptide in an MHC‐restricted fashion. The relevance of these results in the context of vaccine development is discussed.
The tum− antigens P91A and P198 derive from proteins located in the cytosolic compartment of cells
Authors: Verlant Vincent , Amar‐Costesec Alain , Godelaine Danièle , Turu Christine , Van Pel Aline , De Plaen Etienne , Dautry‐Varsat Alice , Beaufay Henri 
Published: March 2007

AbstractTo characterize the proteins P91Ap and P198p, of which mutants generate the tum− antigens P91A and P198, respectively, rabbit antisera were raised with ovalbumin‐coupled synthetic peptides that correspond to their respective C terminus. In immunoadsorption tests using immobilized protein A the antisera recognized the translation products synthesized by rabbit reticulocyte lysates programmed with the SP6 polymerase transcripts of the P91A and P198 cDNA. The presence of the two proteins was demonstrated by SDS‐PAGE and immunoblotting in all the mouse cells and organs examined. P91Ap is a constituent of the cytosol; despite a remarkable homology to the Drosophila diphenol oxidase DOX‐A2, it separates from murine catechol oxidase activity in rate zonal sedimentation analysis. P198p is a ribosomal constituent, or a factor firmly linked to both the free and membrane‐bound ribosomes. These subcellular localizations strengthen other evidence that the antigens presented to T lymphocytes by class I products of the major histocompatibility complex derive from proteins of the cytosol, or in direct contact with it.
Methylation status of immunoglobulin x e segments correlates with their recombination potential
Authors: Goodhardt Michele , Cavelier Patricia , Doyen Noëlle , Kallenbach Sacha , Babinet Charles , Rougeon François 
Published: March 2007

AbstractWe have previously shown that unlike endogenous ϰ genes, unrearranged ϰ transgenes undergo Vϰ‐Jϰ recombination in T as well as B cells of transgenic mice. To determine whether the difference in recombination specificity of the transgenic and endogenous ϰ genes is associated with differences in DNA structure, the methylation status of the endogenous genes and three unrearranged ϰ transgenes was compared. The Jϰ‐Cϰ locus of the transgenes was found to be hypomethylated in all tissues of the transgenic mice. In contrast, methylation of the endogenous ϰ genes was tissue and developmentally regulated. Hypomethylation of the endogenous Jϰ‐Cϰ region occurs only in cells of the B lineage undergoing, or having completed ϰ gene recombination. Transfection of fibroblasts from transgenic and control mice with the recombination activating genes, Rag1 and Rag2, led to a high level of rearrangement of the hypomethylated transgenic, but not the endogenous ϰ genes. These results suggest that hypomethylation defines an accessible state of the ϰ locus and that methylation/demethylation could be involved in the control of ϰ gene rearrangement during lymphocyte differentiation.
Thymus‐derived cytokine(s) including interleukin‐7 induce increase of T cell receptor α/β+ CD4−CD8− T cells which are extrathymically differentiated in athymic nude mice
Authors: Kenai Hiroyuki , Matsuzaki Goro , Nakamura Takao , Yoshikai Yasunobu , Nomoto Kikuo 
Published: March 2007

AbstractExtrathymic T cell differentiation pathways have been reported, although the thymus is the main site of T cell differentiation. The thymus is also known to produce several cytokines that induce proliferation of thymocytes. In the present study, we investigated the influence of thymus‐derived cytokines on extrathymic T cell differentiation by intraperitoneal implantation with a diffusion chamber which encloses fetal thymus (we named it fetal thymus‐enclosed diffusion chamber, FTEDC) in athymic BALB/c nu/nu mice. Increase in number of T cells bearing T cell receptor (TcR) α/β was detected in lymph nodes and spleens of FTEDC‐implanted nude mice 1 week after implantation, whereas no such increase was detected in control nude mice implanted with a diffusion chamber without thymus. The FTEDC‐induced increase of T cells was suppressed by intraperitoneal injection of anti‐interleukin‐7 monoclonal antibody (mAb). The TcR α/β T cells in FTEDC‐inplanted BALB/c nu/nu mice preferentially expressed Vβ11, although Vβ11‐positive T cells are deleted in the thymus of euthymic BALB/c mice by clonal elimination of self‐superantigen Dvb 11‐specific T cells. TcR α/β T cells in FTEDC‐implanted nude mice were of CD4−CD8− phenotype and showed no proliferative response against anti‐TcR monoclonal antibody stimulation. These results suggest that the thymus can induce extrathymic T cell differentiation through the influence of thymus‐derived cytokine(s) including interleukin‐7, and that such extrathymically differentiated T cells have acquired only a little or no ability for proliferation when they recognize antigen by their TcR.
Signaling through the LFA‐1 leucocyte integrin actively regulates intercellular adhesion and tumor necrosis factor‐α production in natural killer cells
Authors: Melero Ignacio , Balboa Maria A. , Aionso Jose L. , Yagüe Enriqueta , Pivel Juan P. , Sanchez‐Madrid Francisco , López‐Botet Miguel 
Published: March 2007

AbstractThe LFA‐1 leucocyte integrin is known to participate in natural killer (NK) cytolytic activity, mediating effector target interactions. The possibility that LFA‐1 may also play an active regulatory role in NK cells has been explored. To this end, we have employed a monoclonal antibody (HP1N) raised against recombinant interleukin‐2 (rIL‐2)‐activated NK cells, which recognizes the α chain of the LFA‐1 heterodimer (CD11a). In contrast to other anti‐CD11a mAb the HP1N and its F(ab)2 fragment did not affect NK cell‐mediated cytotoxicity and triggered a strong homotypic adhesion of NK cells and other LFA‐1+ cells. Cellular aggregation was inhibited by anti‐CD18 mAb, anti‐ICAM‐1 mAb, and other anti‐CD11a mAb. Remarkably, the HP1N mAb was also shown to induce tumor necrosis factor‐α (TNF‐α) production from NK cells upon costimulation with anti‐CD16 mAb. Such an effect appeared to be independent from homotypic adhesion since it took place in Mg2+‐free medium, where NK cell aggregation was inhibited. Moreover, incubation with the HP1N mAb triggered a Ca2+ influx into the cytosol; this effect was clearly observed upon cross‐linking of cell bound HP1N and was also substantiated with other anti LFA‐1 (CD11a and CD18) mAb. Taken together these results indicate that the LFA‐1 molecule is capable of transducing signals in NK cells, which regulate the intercellular interaction with its ligand, and enhance the activation via Fey receptor type III.
Allogeneic recognition of class I molecules: Anti‐H‐2Ld repertoire of H‐2b mice includes T cells recognizing mutant class II H‐2b (Abm12) molecules
Authors: Frangoulis Bernard , Urbero Bruno , Pla Marika 
Published: March 2007

AbstractTwo major histocompatibility complex (MHC) class I‐reactive T cell clones derived from H‐2b mice, generated against the allogeneic Ld molecule, were found to recognize the H‐2b class II mutant Abm12 molecule as well. In addition, these clones also recognize the class II As molecule, and display a class II‐dependent reactivity to staphylococcal enterotoxin B. Neither the class I nor the class II alloreactivities of the clones were found to be dependent on other MHC molecules. Both clones express CD4+CD8− phenotypes. The CD4 molecule appears to be involved in their class II reactivity, while little or no role for CD4 could be detected in the class I reactivity. This is the first report of a class I/class II cross‐reactivity being mediated by CD4+ T cells. The structural basis for this cross‐reactivity is discussed.
The expressed T cell receptor V gene repertoire of rheumatoid arthritis monozygotic twins: Rapid analysis by anchored polymerase chain reaction and enzyme‐linked immunosorbent assay
Authors: Kohsaka Hitoshi , Taniguchi Atsuo , Chen Pojen P. , Ollier William E. R. , Carson Dennis A. 
Published: March 2007

AbstractBecause of heterogeneity in the outbred human population, it has been difficult to determine the genetic factors that influence the expressed T cell receptor (TcR) repertoire in autoimmune diseases. To overcome this problem, we have developed a combination of anchored polymerase chain reaction (APCR) and enzyme‐linked immunosorbent assay (ELISA) that can accurately assess TcR V gene frequencies in numerous clinical samples. The results are independent of amplification efficiency, and Vgene usage can be readily analyzed with an ELISA plate reader and associated software. Using this method, the TcR Vβ gene repertoires in peripheral lymphocytes from nine sets of identical twins, normal, concordant or discordant for rheumatoid arthritis (RA), were studied. The TcR Vγ results were compared with TcR Vβ frequencies in the same specimens as determined by APCR‐ELISA and cDNA sequence analysis. The results showed a marked similarity in the TcR Vβ gene repertoires between identical twins, compared to unrelated subjects (p<0.05) whether or not they were concordant or discordant for RA. In contrast, the TcR Vy gene repertoires in the monozygotic twins differed as much as in controls. The data imply that (a) the human TcR Vβ gene repertoire in peripheral blood is genetically controlled, whereas (b) the TcR Vβ gene repertoire is primarily influenced by environmental stimuli, and (c) RA causes no consistent change in TcR Vβ repertoire of peripheral blood. The APCR‐ELISA method, in the context of large‐scale family and population studies, should facilitate a more precise delineation of the genetic factors that regulate human TcR Vβ expression.
Fcϵ receptor‐positive cells are a major source of antigen‐induced interIeukin‐4 in spleens of mice infected with Schistosoma mansoni
Authors: Williams Megan E. , Kullberg Marika C. , Barbieri Susan , Caspar Patricia , Berzofsky Jay A. , Seder Robert A. , Sher Alan 
Published: March 2007

AbstractWhen cultured in vitro with either mitogen or parasite antigens, spleen cells from mice infected with Schistosoma mansoni produce significantly higher levels of IL‐4 than splenocytes from control animals. Previous studies suggested that this increase in IL‐4 production occurs because of a selective expansion of T helper type 2 (Th2) cells in infected mice. However, these experiments employed unfractionated spleen populations rather than purified T lymphocytes. Here we demonstrate that T‐depleted spleen cells from infected animals synthesize high levels of interleukin‐4 (IL‐4), but no IL‐5 when stimulated with parasite antigen in vitro. Nevertheless, when purified by sorting, T cells and non‐B, non‐T (NBNT) populations produced similar amounts of IL‐4 in response to parasite antigen. The IL‐4 producing NBNT cells were found to belong to an Fee receptor (FceR)‐positive population which after sort purification produced high levels of IL‐4 (between 1000 and 2000 U of per 5 × 103 cells). FACS analysis revealed that these FceR+ cells make up 0.53% of splenic NBNT cells in control animals while in 8‐9‐week‐infected animals they increase to 3.8% of that population. In contrast, in mice with 8‐week unisexual worm infections these cells comprise only 1.71% of NBNT cells, indicating that eggs are a major stimulus of the response. The expansion of FceR+ cells and their production of IL‐4 could be an important factor regulating the selection and induction of different CD4+ subsets in schistosome‐infected hosts.