Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have used the recently cloned cDNA for canine interferon-gamma (IFN-gamma) to engineer bacteria to produce large amounts of the recombinant cytokine. The resulting protein can be recognized by monoclonal and polyclonal antibodies largely species specific for canine IFN-gamma. The purified recombinant IFN-gamma (rIFN-gamma) also had biological activity in vitro in three assay systems: (i) vesicular stomatitis virus plaque inhibition, (ii) class II major histocompatibility complex antigen upregulation on canine kidney parenchymal cells, and (iii) amplification of in vitro tissue-associated lymphoproliferation, all known to be effected by native IFN-gamma (nIFN-gamma). The availability of large amounts of active canine rIFN-gamma will be an important tool in studies of the role of this cytokine in the widely used experimental canine organ transplant model and also will be of diagnostic and therapeutic veterinary interest.
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PMID:Production and characterization of recombinant canine interferon-gamma from Escherichia coli. 850 60

Induction of T-helper cells and T-B cell interaction have been considered to critically depend upon recognition of major histocompatibility complex (MHC) class II molecules by the T cell receptor. Mice lacking either MHC class II molecules (class II(0/0) mice) or its associated invariant chain (Ii0/0 mice) provide new opportunities to test this premise. Immune responses to some protein antigens have been studied in these mice; little is known about their ability to withstand viral infections. We therefore tested CD8+ effector T cells and CD4+ T-cell-dependent B cell function during different viral infections. The vesicular stomatitis virus (VSV)-specific primary cytotoxic T cell response which is largely T-helper-dependent was diminished in Ii(0/0) and absent in class II(0/0) mice. The usually less T-helper-dependent cytotoxic vaccinia or lymphocytic choriomeningitis virus (LCMV)-specific CD8+ T cell responses were reduced up to ninefold in class II(0/0) and up to threefold in Ii(0/0) mice. In class II(0/0) mice, the T-helper-independent neutralizing IgM response against the glycoprotein of VSV was within normal ranges but, in contrast to previous results on CD4(0/0) mice, the T-helper-dependent IgG response was absent. Ii(0/0) mice exhibited a normal neutralizing IgM response; in contrast to class II(0/0) mice, they mounted a significant, though reduced specific IgG response. Similar results were obtained for antibody responses against the nucleoprotein of VSV. Although the T-helper-cell response upon infection with VSV seemed diminished only a little in Ii(0/0) mice, presentation of VSV-G to a class II-restricted specific hybridoma was greater than 300-fold reduced in the absence of Ii. This suggests that local protein concentrations reached during viral infection in the host are high enough to override the Ii deficiency of antigen-presenting cells in vivo.
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PMID:Antiviral immune responses of mice lacking MHC class II or its associated invariant chain. 854 34

Cytotoxic T cells (CTL) recognize target proteins as short peptides presented by major histocompatibility complex (MHC) class I restriction elements. However, there is also evidence for peptide-independent T cell receptor (TCR) recognition of target proteins and non-protein structures. How such T cell responses are generated is presently unclear. We generated carbohydrate (CHO)-specific, MHC-unrestricted CTL responses by coupling di- and trisaccharides to Kb- or Db-binding peptides for direct immunization in mice. Four peptides and three CHO have been analyzed with the CHO either in terminal or central position on the carrier peptide. With two of these glycopeptides, with galabiose (Gal alpha 1-4Gal; Gal2) bound to a homocysteine (via an ethylene spacer arm) in position 4 or 6 in a vesicular stomatitis virus nucleoprotein-derived peptide (RGYVYQGL binding to Kb), CTL were generated which preferentially killed target cells treated with glycopeptide compared to those treated with the core peptide. Polyclonal CTL were also found to kill target cells expressing the same Gal2 epitope in a glycolipid. By fractionation of CTL, preliminary data indicate that glycopeptide-specific Kb-restricted CTL and unrestricted CHO-specific CTL belong to different T cell populations with regard to TCR expression. The results demonstrate that hapten-specific unrestricted CTL responses can be generated with MHC class I-binding carrier peptides. Different models that might explain the generation of such responses are discussed.
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PMID:Immunization with glycosylated Kb-binding peptides generates carbohydrate-specific, unrestricted cytotoxic T cells. 860 19

Immunization of mice with gp96 induces CTL with specificity for proteins that are expressed in the cells from which gp96 was isolated (Arnold et al., J. Exp. Med. 1995. 182: 885, Udono et al., Proc. Natl. Acad. Sci. USA 1994. 91: 3077). Recently, it has been shown that gp96 from cells transfected with vesicular stomatitis virus (VSV) nucleocapsid protein as well as gp96 loaded in vitro with peptides containing an epitope of this protein are taken up by phagocytic cells which obtain thereby the capacity for stimulating VSV-specific cytotoxic T lymphocytes (Suto and Srivastava, Science 1995. 269: 1585). The immunization experiments together with the peptide transfer from gp96/peptide complexes to major histocompatibility complex (MHC) class I molecules of phagocytic cells are consistent with the hypothesis that the endoplasmic reticulum-resident protein gp96 plays a crucial role in the antigen presentation of a cell (Srivastava et al., Immunogenetics 1994. 29: 93). To examine the involvement of gp96 in class I-restricted antigen presentation, we reduced gp96 RNA and protein levels by transfecting P13.1 cells with a vector containing part of gp96 cDNA in antisense orientation to the promotor. We found that antisense clones expressing strongly reduced levels of gp96 mRNA and gp96 protein show normal levels of MHC class I molecules on the cell surface and are recognized by T cells to the same extent as wild-type cells. Thus, our results show that normal levels of gp96 expression in a cell are not limiting for class I-restricted antigen presentation.
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PMID:Expression levels of stress protein gp96 are not limiting for major histocompatibility complex class I-restricted antigen presentation. 862 82

The use of peptides as a vaccine is a potentially powerful immunization strategy. We explored the possibility of inducing an efficient cytotoxic T lymphocyte (CTL) mediated immune response in mice, using in vitro reconstituted major histocompatibility complex (MHC) class I/peptide complexes as the immunogen. Recombinant derived H-2Kb and beta 2-microglobulin (beta 2m) were properly folded into an MHC class I complex using the vesicular stomatitis virus (VSV)-8mer from the natural nucleocapsid proteinN52-59 (RGYVYQGL), an immunodominant Kb epitope in C57BL/6 (B6) mice. After immunizing mice with the H-2Kb class I/VSV peptide complex and a subsequent in vitro stimulation with the VSV peptide alone, a specific CTL response was demonstrated. The method was also applicable to other peptides, for example, the Sendai virus (SV) peptideN324-332 (FAPGNYPAL). The CTL response was mediated by CD3+/CD8+ T cells and was shown to be allele specific, as only peptide loaded target cells expressing the H-2Kb allele could be recognized. It is of interest that extremely small amounts of injected MHC class I/peptide complex (i.e. 500 pg) could generate a measurable CTL response. The MHC class I/peptide complex had to be intact and properly folded to elicit an immune response, suggesting that the complex protected the peptide for internalization by antigen presenting cells (APCs) or for delivering to the proper site for peptide exchange on the cell surface of APCs. The described immunizing method can be routinely used to prime a CTL response by employing in vitro folded MHC class I/peptide complexes, without the use of adjuvants. It appears to be efficient, sensitive and specific. By using the recombinant protein system, unlimited amounts of MHC class I/peptide complex can be produced for immunization. Moreover, this protocol permits different in vitro combinations of allelic MHC class I molecules and peptide variants.
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PMID:In vivo CTL immunity can be elicited by in vitro reconstituted MHC/peptide complex. 869 5

In this report, the kinetics of cellular inflammatory changes in the brain of vesicular stomatitis virus (VSV)-infected C57BL/6 (B6) mice was determined. The behavior and survival rate of infected B6 were carefully monitored each day. Infectious viral titers and VSV antigen distribution were determined at several time points during the course of infection. Strong activation of both astrocytes and microglia was observed after VSV infection. Induction of type II nitric oxide synthase (iNOS) was detected in activated microglia in the olfactory bulb (OB) starting at day 4 postinfection. Induced expression of major histocompatibility complex (MHC) molecules and rapid infiltration of both T cells and natural killer (NK) cells were detected in the VSV-infected CNS. Collectively, these data indicate that the response to CNS infection in B6 mice, which is often primarily Th1 in characteristics, is comparable to BALB/c mice, a strain that often shows a Th2-dominated immune response.
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PMID:Host immune response to vesicular stomatitis virus infection of the central nervous system in C57BL/6 mice. 889 Apr 78

Studies of hamster-human and mouse-human somatic fibroblast hybrids and transfected mouse fibroblasts have demonstrated that signaling through the human interferon-gamma receptor (hu-IFN-gammaR) requires the formation of a complex consisting of ligand (IFN-gamma), a ligand binding receptor chain (IFN-gammaR1), and a signal transducing receptor chain (IFN-gammaR2). To date, the ability of this receptor complex to transduce the full repertoire of biological signals has been difficult to assess due to the limited number of activities that IFN-gamma can exert on fibroblasts. The current report assesses the ability of hu-IFN-gammaR chains to transduce signals in the absence of background human gene products by expressing hu-IFN-gammaR2 in a transformed macrophage cell line (F10/96) derived from a hu-IFN-gammaR1 transgenic mouse. Our results indicate that F10/96 clones expressing both human receptor proteins bind hu-IFN-gamma with an affinity comparable to that of human cells. Binding of either human or mouse IFN-gamma to its respective receptor elicits classic IFN-gamma responses such as up-regulation of major histocompatibility complex antigens, enhanced expression of IRF-1, and increased production of NO2- radicals, interleukin-6, tumor necrosis factor-alpha, and granulocyte macrophage-colony stimulating factor. However, hu-IFN-gamma could not fully protect the clones from cytopathic effects of encephalomyocarditis virus and vesicular stomatitis virus while mo-IFN-gamma could. These results demonstrate that while co-expression of hu-IFN-gammaR1 and hu-IFN-gammaR2 is necessary and sufficient for most IFN-gamma-induced responses, it is not sufficient to confer a generalized antiviral state. These findings further suggest that additional species-specific accessory factor(s) are necessary for full signaling potential through the IFN-gamma receptor complex. The nature and potential role of such factors in IFN-gammaR signaling is discussed.
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PMID:Mouse macrophages carrying both subunits of the human interferon-gamma (IFN-gamma) receptor respond to human IFN-gamma but do not acquire full protection against viral cytopathic effect. 895 96

The development of safe and effective vaccines remains a major goal in the prevention, and perhaps treatment, of infectious diseases. Ideally, a single vaccine would confer protection against several pathogens and would induce both cellular and humoral arms of the immune response. We originally demonstrated that two virus-specific cytotoxic T-lymphocyte (CTL) epitopes, from the same virus but presented by different major histocompatibility complex alleles, when linked in tandem as minigenes in a recombinant vaccinia virus, could confer complete protection against subsequent viral challenge. In the study, we extended this approach, which we termed string of beads, expanding the immunogenic scope in two ways: first, by introduction of T helper (Th) and B-cell (antibody) epitopes alongside CTL epitopes and second, by including immunogenic sequences from a variety of infectious agents, five viruses and one bacterium. The vaccine (VV-sv) comprises CTL epitopes from Sendai virus, respiratory syncytial virus, and lymphocytic choriomeningitis virus (LCMV); Th epitopes from vesicular stomatitis virus and Mycobacterium tuberculosis; and an antibody epitope from mengovirus. The construct contains a single start codon, and the epitopes are linked directly, without intervening spacer amino acids. There was some concern that the combination of several normally immunodominant epitopes might result in a new hierarchy of dominance, in which certain epitopes predominated and others exhibited reduced immunogenicity. However we show that when analyzed in tissue culture and in vivo, all six epitopes are expressed. CTL and Th cells are induced in vivo, along with neutralizing antibody. The induced immunity is biologically relevant: after VV-sv immunization, the antimengovirus antibody confers protection against mengovirus challenge. Similarly, CTL induced by the LCMV epitope protected mice against challenge with this agent. Thus, a polyvalent, minigene-based vaccine can simultaneously induce several classes of immune response and thereby can confer protection against diverse pathogens.
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PMID:A multivalent minigene vaccine, containing B-cell, cytotoxic T-lymphocyte, and Th epitopes from several microbes, induces appropriate responses in vivo and confers protection against more than one pathogen. 903 65

Infusion of interleukin-12 (IL-12) enhances recovery from lethal experimental vesicular stomatitis virus (VSV) infection of the central nervous system (CNS). Interleukin-12 treatment resulted in: 1) increased survival frequency; 2) faster recovery from weight loss; 3) substantially decreased VSV titers in brain homogenates and diminished immunohistochemical detection of VSV antigens in tissue sections; 4) earlier and increased CNS expression of types 1, 2, and 3 nitric oxide synthase (NOS) and both major histocompatibility complex (MHC) class I and class II antigens; 5) earlier and increased blood and CNS levels of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). These results suggest that IL-12 enhances recovery from VSV infection of the CNS.
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PMID:Interleukin-12 promotes recovery from viral encephalitis. 909 30

To investigate negative selection events during intrathymic ontogeny, we established T cell receptor (TCR)-transgenic mice [N15tg/RAG-2-/- (H-2b)] expressing a single TCR specific for vesicular stomatitis virus nuclear octapeptide N52-59 (VSV8) in the context of the major histocompatibility complex (MHC) class I molecule, K(b). Administration of VSV8 in vivo induced apoptosis in less than 4 h, deleting the majority of immature double-positive (DP) thymocytes by 24 h. In contrast, DP TCRhigh as well as single-positive (SP) thymocytes were refractory to this death process. Moreover, DP TCRhigh cells differentiated into SP thymocytes in vitro and in vivo, maturing into functional cytotoxic T lymphocytes upon intrathymic transfer to beta RAG 2-/- recipients. Hence, negative selection processes involving MHC-bound peptide ligands are operative only prior to the late DP thymocyte stage in this MHC class I-restricted TCR transgene system.
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PMID:Double-positive T cell receptor(high) thymocytes are resistant to peptide/major histocompatibility complex ligand-induced negative selection. 934 70


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