bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential antigen recognition by T cell populations from strains of mice developing polar forms of granulomatous inflammation in response to eggs of Schistosoma mansoni
Authors: Hernandez Hector J. , Trzyna Wendy C. , Cordingley John S. , Brodeur Peter H. , Stadecker Miguel J. 
Published: March 2007

AbstractIn humans, infection with schistosome helminths can lead to dissimilar forms of clinical disease. Likewise, in the experimental mouse system, identical infection protocols with Schistosoma mansoni cause a more severe granulomatous disease in the C3H strain than in the C57BL/6 strain. To address this difference, we developed panels of schistosomal egg antigen (SEA)‐specific T cell hybridomas to compare the responses of C3H and C57BL/6 mice to the major egg antigen p40. All derived C3H T cell hybridomas, despite being clonally distinct and restricted by either I‐Ak or I‐Ek, responded to recombinant fragment 15‐1 of the p40 antigen, while none of the C57BL/6 T cell hybridomas did. Consistent with the observed monoclonal T cell responses, polyclonal lymph node cells from schistosome‐infected C3H mice reacted strongly to fragment 15‐1, which contrasted sharply with the weak response displayed by the C57BL/6 strain. Moreover, studies with congenic mice demonstrated that the strong CD4+ T cell response to fragment 15‐1 was under major histocompatibility complex control and segregated with the H‐2k haplotype. These findings suggest that a dominant T cell response against a major egg antigen may represent a risk factor for the development of severe disease.
Altered Th1/Th2 balance associated with non‐major histocompatibility complex genes in collagen‐induced arthritis in resistant and non‐resistant rat strains
Authors: Müssener Åsa , Lorentzen Johnny C. , Kleinau Sandra , Klareskog Lars 
Published: March 2007

AbstractCollagen‐induced arthritis (CIA) is a T cell‐dependent disease in which susceptibility is controlled by genes both within and outside the major histocompatibility complex (MHC). In the present study, we compared the humoral responses and kinetics of cytokine secretion patterns in the draining lymph nodes of arthritis‐susceptible DA rats and arthritis‐resistant F344 and DA MHC congenic PVG.1AV1 rats immunized with rat type II collagen (RCII) in incomplete Freund's adjuvant. The results demonstrate a marked humoral RCII response and a Th1 cytokine profile, with expression of interferon‐γ and interleukin (IL)‐2 mRNA in DA rats; a limited humoral RCII response and a Th2 cytokine profile, with expression of IL‐4 mRNA in arthritis‐resistant F344 rats; and a marked humoral RCII response in arthritis‐resistant PVG.1AV1 rats. However, in contrast to DA rats, PVG.1AV1 rats produce IgG1 autoantibodies which, together with strong expression of IL‐4 mRNA, indicates the involvement of Th2 subsets. From these data, we conclude that non‐MHC gene(s) determines the direction of the anti‐RCII response towards a Th1 disease‐promoting, or a Th2 disease‐limiting response.
Transgenic expression of a CD46 (membrane cofactor protein) minigene: Studies of xenotransplantation and measles virus infection
Authors: Thorley Bruce R. , Milland Julie , Christiansen Dale , Lanteri Marc B. , McInnes Beth , Moeller Ingrid , Rivailler Pierre , Horvat Branka , Rabourdin‐Combe Chantal , Gerlier Denis , McKenzie Ian F. C. , Loveland Bruc. E. E. 
Published: March 2007

AbstractCD46 (membrane cofactor protein) is a human cell‐surface regulator of activated complement and a receptor for the measles virus. A CD46 transgenic mouse line with an expression pattern similar to that of human tissues has been produced, to develop an animal model of (i) the control of complement activation by complement regulators in hyperacute rejection of xenografts, and (ii) measles virus infection. The mouse line was made using a CD46 minigene that includes promoter sequence and the first two introns of genomic CD46, which was coinjected into mouse ova with chicken lysozyme matrix attachment region DNA. A high level of CD46 expression in homozygotic transgenic mice was obtained with spleen cells having approximately 75% of the level found on human peripheral blood mononuclear cells. CD46 was detected in all tissues examined by immunohistochemistry, radioimmunoassay and Western blotting, showing that these mice were suitable for transplantation and measles virus infection studies. It also indicated that the transgene included the important regulatory elements of the CD46 promoter. Transgenic spleen cells were significantly protected in vitro from human complement activated by either the classical or alternative pathways and from alternative pathway rat complement. Furthermore, transgenic mouse hearts transplanted to rats regulated complement deposition in an in vivo model of antibody‐dependent hyperacute xenograft rejection. Similar to human lymphocytes, transgenic lymphoblasts could be infected in vitro with measles virus; infected cells expressed viral proteins and produced infectious viral particles. The data demonstrate the suitability of this minigene for obtaining high‐level CD46 expression sufficient for enhanced resistance of transgenic cells to complement attack and for obtaining wide tissue distribution of CD46, analogous to human tissues and, therefore, useful for comparative studies.
Pax‐5 is identical to EBB‐1/KLP and binds to the VpreB and λ5 promoters as well as the KI and KII sites upstream of the Jχ genes
Authors: Tian Jiayuan , Okabe Taijiro , Miyazaki Takahiro , Takeshita Sunao , Kudo Akira 
Published: March 2007

AbstractDuring B cell differentiation, the pre‐B cell stage plays a significant role in immunoglobulin gene rearrangement in the context of the allelic exclusion and χ chain gene rearrangement. We previously reported that the early B cell‐specific binding protein (EBB)‐1 transcription factor binds to the promoters of two pre‐B cell‐specific genes, VpreB and λ5, and regulates their pre‐B cell‐specific expression. Here, we demonstrate that EBB‐1 binds to the KI and KII sites in the upstream of Jχ region, which are crucial for χ chain gene rearrangement. Gene transfer and gel‐shift assays demonstrate that EBB‐1 is identical to Pax‐5 and binds to promoters of VpreB and λ5 as well as the KI and KII sites. Our results suggest that Pax‐5 plays an important role in the coordinate regulation of several immunoglobulin gene family members that are crucial in B cell development.
The T cell receptor β genes of Xenopus
Authors: Chrétien Isabelle , Marcuz Anne , Fellah Julien , Charlemagne Jacques , Pasquier Louis Du 
Published: March 2007

AbstractcDNA of the T cell receptor β (TCRB) have been isolated from the anuran amphibian Xenopus and they show strong structural homology to TCRB sequences of other vertebrates. Ten BV families, two D segments, ten J segments, and a single C region have been defined so far. Each V family consists of one to two members per haploid genome. A unique feature of the Xenopus TCRB constant region is the lack of N‐linked carbohydrate glycosylation sites. The recombination signal sequences suggest that the mechanism of rearrangements are identical to those of mammals. The locus is inherited in a diploid manner despite the pseudotetraploidy of the Xenopus laevis and X. gilli used in this study.
Carboxy‐terminal residues of major histocompatibility complex class II‐associated peptides control the presentation of the bacterial superantigen toxic shock syndrome toxin‐1 to T cells
Authors: Wen Renren , Broussard Dana R. , Surman Sherri , Hogg Twala L. , Blackman Marcia A. , Woodland David L. 
Published: March 2007

AbstractPrevious studies have shown that the presentation of some bacterial superantigens by major histocompatibility complex (MHC) class II molecules is strongly influenced by class II‐associated peptides. For example, presentation of the toxic shock syndrome toxin‐1 (TSST‐1) superantigen by antigen‐processing‐defective T2‐I‐Ab cells (which expresses I‐Ab that is either empty or associated with invariant chain‐derived peptides) can be strongly enhanced by some, but not other, I‐Ab‐binding peptides. Here we investigate the contribution of I‐Ab‐associated peptides in the presentation of TSST‐1 to T cells. The data show that overlapping peptides expressing the same core I‐Ab‐restricted epitope, but with various N and C termini, can differ profoundly in their ability to promote TSST‐1 presentation to T cells. Analysis of altered and truncated peptides indicates that residues at the C‐terminal end of the peptide have a dramatic effect on TSST‐1 presentation. This effect does not involve a cognate interaction between the peptide and the TSST‐1 molecule, but appears to depend on the length of the C‐terminal region. These data are consistent with crystallographic studies suggesting that TSST‐1 may interact with the C‐terminal residues of MHC class II‐associated peptides. We also examined the capacity of naturally processed peptides to promote TSST‐1 binding using a superantigen blocking assay. The data demonstrated that a naturally processed epitope is dominated by peptides that do not promote strong TSST‐1 binding to I‐Ab. Taken together, these data suggest that TSST‐1 binding to MHC class II molecules is controlled by the C‐terminal residues of the associated peptide, and that many naturally processed peptide/class II complexes do not present TSST‐1 to T cells. Thus, the peptide dependence of TSST‐1 binding to class II molecules may significantly reduce the capacity of TSST‐1 to stimulate T cells.
Superantigen and endotoxin synergize in the induction of lethal shock
Authors: Blank Christian , Luz Arne , Bendigs Sylvia , Erdmann Andreas , Wagner Hermann , Heeg Klaus 
Published: March 2007

AbstractEndotoxin (lipopolysaccharide; LPS) and superantigens (exotoxins) have been identified as potent inducers of lethal shock. While endotoxin primarily interacts with CD 14 receptors on macrophages, superantigens like the staphylococcal enterotoxin B (SEB) preferentially activate T cells. Both cell types are triggered to release pro‐inflammatory cytokines that in turn induce lethal shock. We analyzed whether endotoxin and superantigen interact during the induction phase of lethal shock. We report that LPS and SEB operate synergistically. Lethal doses of both inducers were reduced 100‐fold when given in combination. The induced serum levels of tumor necrosis factor, interleukin‐6, and interferon‐γ (IFN‐γ) were elevated and remained high for a prolonged period. Moreover, synergistic action of LPS and SEB induced lethal toxic shock even without presensitization of mice with D‐galactosamine (D‐GalN). Opposed to D‐GalN‐pretreated mice, mice injected with LPS and SEB showed less liver damage, but rather apoptosis of epithelial cells in the bowel. Cyclosporin A and treatment with anti‐IFN‐γ monoclonal antibody blocked the synergistic action of LPS and SEB, indicating that T cell‐derived IFN‐γ is the mediator of the observed synergism. Concomitant injection of LPS and SEB had no influence on SEB‐induced T cell deletion and anergy induction. Since Gram‐positive and Gram‐negative bacteria can be recovered from septic blood samples, the synergistic action of endotoxin and superantigens might be relevant during lethal septicemia.
Naive alloreactive CD8 T cells are activated by purified major histocompatibility complex class I and antigenic peptide
Authors: Goldstein Julia , Mostowsky Howard , Tung Joyce , Hon Huiming , Brunswick Mark , Kozlowski Steven 
Published: March 2007

AbstractIn this report, we demonstrate stimulation of T cell receptor (TCR) transgenic CD8 T cells by isolated major histocompatibility complex (MHC) class I H‐2Ld complexes and antigenic peptide. This is the first demonstration of CD8 T cells activated by MHC and antigenic peptide in the absence of antigen priming. Furthermore, isolated MHC and a potent peptide antigen can stimulate phenotypically naive CD44− T cells to become CTL effectors and to produce interleukin‐2 in nanogram per milliliter amounts. These results demonstrate that particular TCR antigen pairs may overcome the need for specialized antigen‐presenting cells and have implications for mechanisms of autoimmunity and tolerance induction.
Surfactant protein A, but not surfactant protein D, is an opsonin for influenza A virus phagocytosis by rat alveolar macrophages
Authors: Benne Cornelis A. , Benaissa‐Trouw Barry , Van Strijp Jos A. G. , Kraaijeveld Cornelis A. , Van Iwaarden J. Freek F. 
Published: March 2007

AbstractSurfactant protein A (SP‐A) and surfactant protein D (SP‐D) are collectins, and both proteins were shown to interact with influenza A virus and alveolar macrophages. However, it is not known whether SP‐A and SP‐D can serve as opsonins for the phagocytosis of influenza A virus by alveolar macrophages. In the present study, we investigated the opsonic activities of SP‐A and SP‐D for phagocytosis of fluorescein isothiocyanate (FITC)‐labeled influenza A (H3N2) virus by rat alveolar macrophages using flow cytometry. SP‐A enhanced the association of the virus with macrophages in a dose‐dependent manner, reaching a maximum at an SP‐A concentration of 60 μg/ml. An approximate threefold increase in association of influenza A virus with alveolar macrophages in the presence of SP‐A over control incubations which contained no SP‐A was observed. Half of the total cell‐associated fluorescence could be quenched as demonstrated using the extracellular quenching dye trypan blue. These results indicate that SP‐A mediates internalization of FITC‐labeled influenza A (H3N2) virus by alveolar macrophages. Removal of the carbohydrate moiety of SP‐A by N‐glycosidase F treatment or cleavage of its sialic acid residues by neuraminidase abolished the enhancement of the phagocytosis of FITC‐labeled influenza A virus by alveolar macrophages. Mannan, a mannose homopolysaccharide known to bind to the carbohydrate‐binding domain of SP‐A, did not affect the SP‐A‐mediated phagocytosis of FITC‐labeled influenza by alveolar macrophages. In contrast, SP‐D neither enhanced the association of FITC‐labeled influenza A virus with alveolar macrophages nor affected the opsonic activity of SP‐A for FITC‐labeled influenza A (H3N2) virus at the SP‐D concentrations tested. It is concluded that SP‐A acts via its sialic acid residues as an opsonin in the phagocytosis of influenza A virus by alveolar macrophages.
Expression of two interleukin‐15 mRNA isoforms in human tumors does not correlate with secretion: role of different signal peptides
Authors: Meazza Raffaella , Gaggero Alessia , Neglia Francesca , Basso Stefania , Sforzini Sabrina , Pereno Raffaele , Azzarone Bruno , Ferrini Silvano 
Published: March 2007

AbstractInterleukin (IL)‐15 is a four‐helix bundle cytokine sharing several biological properties with IL‐2. By reverse transcriptase‐polymerase chain reaction analysis, human cancer cell lines of different histotypes are shown to express two IL‐15 amplification products: a 524‐bp band corresponding to the IL‐15 mRNA found in macrophages, and another of 643 bp corresponding to an alternatively spliced mRNA including a 119‐bp alternative exon. IL‐15 was undetectable in the supernatant of tumor cell lines expressing either one or both of the mRNA isoforms as evaluated by a bioassay or by ELISA, indicating that IL‐15 is not secreted. However, IL‐15 could be detected intracellularly in some tumor cells by confocal microscopy analysis. Since the pre‐proteins encoded by the two mRNA isoforms differ in the signal peptide sequence, we have analyzed the characteristics of these signal peptides and their possible role in controlling secretion. The two IL‐15 cDNA isoforms, expressed in COS‐7 cells, induced very low levels of IL‐15 secretion. However, substitution of the sequence encoding natural signal peptide(s) with the one from IgVχ chain in the IL‐15 cDNA results in a significantly higher secretion of biologically active IL‐15 (15–30‐fold) upon cDNA transfection. A poor efficiency of natural signal peptides may represent one of the mechanisms involved in the control of IL‐15 secretion.
RANTES stimulation of T lymphocyte adhesion and activation: role for LFA‐1 and ICAM‐3
Authors: Szabo Margit C. , Butcher Eugene C. , McIntyre Bradley W. , Schall Thomas J. , Bacon Kevin B. 
Published: March 2007

AbstractThe chemokine RANTES is a potent chemoattractant and activator of T lymphocytes. Mechanisms underlying the RANTES‐induced activation of T lymphocytes leading to adhesion and migration have not been fully analyzed. We investigate here the function of RANTES in the regulation of T cell adhesion, specifically the induction of homotypic aggregation. RANTES induced the expression of many important cell surface adhesion and activation receptors in a normal human T cell clone and peripheral blood T lymphocytes, including members of the β1 and β2 integrin family, CD44, CD50, and CD28. Up‐regulation of these markers correlated with RANTES‐stimulated homotypic adhesion of T cells. This homotypic aggregation event was RANTES dose‐dependent, prolonged, and pertussis toxin‐independent, but herbimycin A‐sensitive, suggesting that it involves signaling through alternative (Gαi protein‐independent) pathways. Using specific monoclonal antibodies, the homotypic aggregation event was shown to be lymphocyte function‐associated antigen‐1 (LFA‐1)‐dependent, with no observable interaction through α4 or β1 integrins. Intercellular adhesion molecule‐3 (ICAM‐3) and possibly ICAM‐1 participate as LFA‐1 ligands. Additionally, RANTES phosphorylated the β chain of LFA‐1 1–2 min following stimulation. These results imply a specific role for the chemokine RANTES in T cell activation and intercellular adhesion.
Cytokine induction of monocyte chemoattractant protein‐1 gene expression in human endothelial cells depends on the cooperative action of NF‐χB and AP‐1
Authors: Martin Teresa , Cardarelli Pina M. , Parry Graham C. N. , Felts Katherine A. , Cobb Ronald R. 
Published: March 2007

AbstractChemokines are potent mediators of cell migration and activation and therefore play an essential role in early events of inflammation. In conjunction with cell adhesion molecules, chemokines help to localize cells to a specific site and enhance the inflammatory reaction at the site. Clinically, elevated levels of chemokines have been found in a variety of inflammatory diseases. The prototype C‐C chemokine is monocyte chemoattractant protein‐1 (MCP‐1) which is synthesized by a variety of cell types including endothelial cells in response to a variety of stimuli. MCP‐1 is a major chemoattractant for monocytes, T lymphocytes, and basophils. In the present study, we investigated the factors involved in cytokine‐induced MCP‐1 gene expression in human endothelial cells. We present evidence that the nuclear factor (NF)‐χB‐like binding site and the AP‐1 binding site located 90 and 68 base pairs upstream of the transcriptional start site, respectively, are required for maximal induction of the human MCP‐1 promoter by interleukin‐(IL)‐1β. Site‐directed mutagenesis or deletion of the NF‐χB‐like site decreased the cytokine‐induced activity of the promoter. Site‐directed mutagenesis of the AP‐1 binding site also decreased the cytokine‐induced activity of the promoter. We show that the NF‐χB‐like site located at −90 in the MCP‐1 promoter binds to the p50/p65 heterodimer of the NF‐χB/Rel family in IL‐1β‐stimulated human endothelial cells. Overexpression of p65 results in the transactivation of the MCP‐1 promoter as well. The data presented in this study suggest that cytokine‐induced MCP‐1 gene expression in human endothelial cells depends on the cooperative action of NF‐χB and AP‐1.
Agonist antibody and Fas ligand mediate different sensitivity to death in the signaling pathways of Fas and cytoplasmic mutants
Authors: Thilenius Anja R. B. , Braun Kari , Russell John H. 
Published: March 2007

AbstractWe have produced three forms of human Fas: full‐length Fas, Fas with a C‐terminal deletion, and a chimera between extracellular Fas and the intracellular domain of the tumor necrosis factor receptor I p55 subunit. We transfected cell lines with these constructs to compare the relative capacity of antibody agonists and the physiological Fas ligand (FasL) to stimulate death. With two agonistic antibodies, the chimera is 100‐ to 1000‐fold more sensitive to induction of death than the full‐length Fas. The C‐terminal deletion mutant also shows greatly enhanced death in comparison to the wild‐type receptor. In contrast, when FasL is used to trigger the Fas pathway, wild‐type Fas and the deletion mutant are similarly sensitive, whereas the chimera is 100‐fold less susceptible to ligand‐mediated killing than Fas. This demonstrates that antibody agonists and natural ligand can stimulate different signaling pathways and emphasizes the limitations of defining physiologically important signaling pathways solely by antibody agonists.
The HER2/neu‐derived peptide p654–662 is a tumor‐associated antigen in human pancreatic cancer recognized by cytotoxic T lymphocytes
Authors: Peiper Matthias , Goedegebuure Peter S. , Linehan David C. , Ganguly Eric , Douville Cara C. , Eberlein Timothy J. 
Published: March 2007

AbstractThe protooncogene HER2/neu encodes a 185‐kDa transmembrane protein with extensive homology to the epidermal growth factor receptor. It is overexpressed in several human cancers of epithelial origin, such as pancreatic cancer. Previously, we demonstrated that cytotoxic T lymphocytes (CTL) derived from breast, ovarian, and non‐small cell lung cancer recognized a peptide derived from HER2/neu. To evaluate whether this HLA‐A2‐binding peptide is a tumor‐associated antigen (TAA) in pancreatic cancer, the ability of HER2/neu‐reactive CTL to lyse human pancreatic carcinoma cells was tested. CTL were generated from tumor‐associated T lymphocytes from HLA‐A2+ HER2/neu+ breast and ovarian cancer patients. All CTL recognized autologous and allogeneic HER2/neu+ tumor cells in an HLA‐A2‐restricted fashion. Furthermore, all CTL recognized p654–662 (GP2) derived from HER2/neu. These CTL also recognized HER2/neu+ pancreatic cancer cells in an HLA‐A2‐restricted fashion. HER2/neu+ HLA‐A2− pancreatic cancer cells were not or only poorly lysed. Repeated stimulation of HLA‐A2+ PBL from pancreatic cancer patients using the HER2/neu‐derived peptide resulted in specific recognition of this peptide and, more importantly, HER2/neu+ pancreatic tumors in an HLA‐A2‐restricted fashion. Autologous HLA‐A2+ fibroblasts or HLA‐A2+ malignant melanoma cells were not recognized. HLA‐A2− peptide‐stimulated T lymphocytes showed no significant cytotoxicity. These results demonstrate that this HER2/neu‐derived peptide is a shared TAA among several adenocarcinomas including pancreatic carcinoma, suggesting a common mechanism of recognition of these human tumors by T lymphocytes. The identification of the HER2/neu‐derived peptide GP2 as a TAA in pancreatic cancer provides an opportunity for the design of novel immunotherapy and vaccine strategies.