Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Cytotoxic thymus-derived lymphocytes from mice infected with vesicular stomatitis virus (VSV) are H-2 restricted and virus specific for the Indiana and New Jersey strains of VSV. VSV-Indiana-immune T cells can lyse target cells infected with the temperature sensitive (ts) mutant ts 045 about 30 times better when target cell infection occurs at the permissive rather than the non-permissive temperature. Since this mutant fails to express the glycoprotein at the cell surface when grown at the nonpermissive temperature, our results support the view that the viral glycoprotein is involved in defining the major target antigen for VSV-specific T cells. However, the tl 17 mutant that expresses a mutant glycoprotein at the cell surface was lysed, suggesting that the expressed mutated glycoprotein can cross-react with Indiana wild-type glycoprotein. Targets infected at the nonpermissive temperature with VSV ts G31 (mutant in the matrix protein) are still susceptible to T cell-mediated lysis but at a lower level of sensitivity. These results are compatible with the interpretation that for VSV-specific T cell lysis of infected target cells, the viral glycoprotein is a major target antigen and must be expressed, and that the matrix protein plays a lesser role, probably by indirectly influencing glycoprotein configuration at the cell surface.
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PMID:Target antigens for H-2-restricted vesicular stomatitis virus-specific cytotoxic T cells. 21 Feb 32

Mechanisms of antigen processing and presentation to thymus-derived lymphocytes have been under intense study for several years, focusing on both Class I-restricted antigen presentation and Class II-MHC restricted responses. The studies described here examine the processing and presentation of exogenously provided soluble glycoprotein of the vesicular stomatitis virus and as well as newly synthesized viral glycoprotein. Evidence is provided that newly synthesized Class II MHC chains are required for cell surface expression of processed glycoprotein determinants irrespective of the origin of the viral antigen. Inhibitors of distinct cellular processes, including ammonium chloride, emetine, and Brefeldin A, have been used to dissect the pathways utilized.
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PMID:Newly synthesized class II MHC chains are required for VSV G presentation to CTL clones. 130 89

T lymphocytes recognize antigens as peptide fragments associated with molecules encoded by the major histocompatibility complex (MHC) and expressed on the surface of antigen-presenting cells. In the thymus, T cells bearing alpha beta receptors that react with the MHC molecules expressed by radioresistant stromal elements are positively selected for maturation. In (A x B-->A) bone marrow chimaeras, T cells restricted to the MHC-A haplotype are positively selected, whereas MHC-B-reactive thymocytes are not. We investigated whether the introduction of particular thymic stromal elements bearing MHC-B molecules could alter the fate of B-reactive T cells in these (A x B-->A) chimaeras. Thymic epithelial cell (TEC) lines expressing H-2b were introduced by intrathymic injection into (H-2b/s-->H2s) bone marrow chimaeras and we measured their ability to generate H-2b-restricted cytotoxic T-lymphocytes (CTLs). We report here that one TEC line, 427.1, was able positively to select CTLs specific for influenza and vesicular stomatitis virus antigens in association with class I H-2b molecules. In addition, line 427.1 can process cytoplasmic proteins for presentation to H-2Kb- and H-2Db-restricted CTLs. Thus, a TEC line capable of normal class I MHC antigen processing and presentation in vitro can induce positive selection after intrathymic injection.
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PMID:Positive selection of T-lymphocytes induced by intrathymic injection of a thymic epithelial cell line. 133 4

I have compared the requirements for T helper (Th) cell function during the generation of virus-specific and alloreactive cytotoxic thymus (T)-derived lymphocyte (CTL) responses. Restimulation of vesicular stomatitis virus (VSV)-immune T cells (VSV memory CTLs) with VSV-infected stimulators resulted in the generation of class I-restricted, VSV-specific CTLs. Progression of VSV memory CTLs (Lyt-1-2+) into VSV-specific CTLs required inductive signals derived from VSV-induced, Lyt-1+2- Th cells because: (i) cultures depleted by negative selection of Lyt-1+ T cells failed to generate CTLs; (ii) titration of VSV memory CTLs into a limiting dilution (LD) microculture system depleted of Th cells generated curves which were not consistent with a single limiting cell type; (iii) LD analysis of VSV memory CTLs did produce single-hit curves in the presence of Lyt-1+2- T cells sensitized against VSV; and (iv) monoclonal anti-L3T4 antibody completely abrogated CTL generation against VSV. Similar results were also obtained with Sendai virus (SV), a member of the paramyxovirus family. The notion that a class II-restricted, L3T4+ Th cell plays an obligatory role in the generation of CTLs against these viruses is also supported by the observation that purified T cell lymphoblasts (class II antigen negative) failed to function as antigen-presenting cells for CTL responses against VSV and SV. T cell lymphoblasts were efficiently lysed by class I-restricted, anti-VSV and -SV CTLs, indicating that activated T cells expressed the appropriate viral peptides for CTL recognition. Furthermore, heterogeneity in the VSV-induced Th cell population was detected by LD analysis, suggesting that at least two types of Th cells were required for the generation of an anti-VSV CTL response. VSV-induced Th cell function could not simply be replaced by exogenous IL-2 because this lymphokine induced cytotoxic cells that had the characteristics of lymphokine-activated killer (LAK) cells and not anti-viral CTLs. In contrast, CTL responses against allogeneic determinants could not be completely blocked with antibodies against L3T4 and depletion of L3T4+ cells did not prevent the generation of alloreactive CTLs in cultures stimulated with allogeneic spleen cells or activated T cell lymphoblasts. Thus, these studies demonstrate an obligatory requirement for an L3T4-dependent Th cell pathway for CTL responses against viruses such as VSV and SV; whereas, CTL responses against allogeneic determinants can utilize an L3T4-independent pathway.
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PMID:T helper cells in cytotoxic T lymphocyte development: role of L3T4(+)-dependent and -independent T helper cell pathways in virus-specific and alloreactive cytotoxic T lymphocyte responses. 215 64

We have evaluated the efficacy of mitogen (LPS/DxSO4)-activated B cells (B lymphoblasts) to function as antigen-presenting cells (APC) for vesicular stomatitis virus (VSV). Our studies revealed that B lymphoblasts induced potent cytotoxic thymus (T)-derived lymphocyte (CTL) activity in VSV-immune splenic T cells depleted of adherent accessory cells. Dose-response curves indicated that B lymphoblasts were approximately 15-20 times more efficient APC than spleen cells for CTL induction against VSV. There was little evidence of reprocessing of viral antigens by the responder population because only CTL activity restricted to the parental haplotype of the B lymphoblast was generated following stimulation of VSV-immune F1 T cells. B lymphoblasts activated VSV-specific memory CTL which expressed the Lyt-1-23+, AsGM1+ phenotype without activating natural killer and/or lymphokine-activated killer cells. The ability of B lymphoblasts to function as efficient APC was not related to enhanced viral replication in these cells because potent VSV-specific proliferative and class I-restricted CTL responses were induced by B lymphoblasts infected with VSV rendered noninfectious by exposure to ultraviolet (uv) light. This indicates that activated B cells can efficiently process and present input virion protein. Purified splenic B cells that were not activated by mitogen stimulation did not function as APC for VSV even at high multiplicities of infection. The failure of B cells to function as APC for VSV was related to inefficient uptake of VSV and their inability to provide accessory cell signals required for T-cell proliferation; both these functions developed following mitogen stimulation. These data suggest that activated B cells may function as a potent APC population for virus independent of the specificity of their immunoglobulin antigen receptor.
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PMID:Antigen-presenting B cells: efficient uptake and presentation by activated B cells for induction of cytotoxic T lymphocytes against vesicular stomatitis virus. 283 71

Ten ribonucleic acid (RNA) tumor viruses grown in five different host cell species and three non-oncogenic viruses from three different virus groups have been examined for ribonuclease H content. Three different substrates were used to assay ribonuclease H: calf thymus [(3)H]RNA-deoxyribonucleic acid (DNA) hybrid prepared with denatured calf thymus DNA and Escherichia coli DNA-directed RNA polymerase, (3)H-polydenylic acid [(3)H-poly(A)] complexed to polydeoxythymidylic acid [poly(dT)], and (3)H-polyuridylic acid [(3)H-poly(U)] complexed to polydeoxyadenylic acid [poly(dA)]. All ten RNA tumor viruses contained ribonuclease H activity which degraded the RNA of both the calf thymus hybrid and poly(A)-poly(dT), whereas only the ribonuclease H in the Moloney strain of murine sarcoma-leukemia virus and in RD-feline leukemia virus hydrolyzed the RNA strand of poly(U)-poly(dA). No appreciable ribonuclease H activity was detected in influenza, Sendai, or vesicular stomatitis virus. The ribonuclease H and RNA-directed DNA polymerase activities in Moloney murine sarcoma-leukemia virus were inseparable by phosphocellulose chromatography or glycerol gradient centrifugation, but appeared to be partially separated by diethylaminoethyl-cellulose chromatography.
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PMID:Ribonuclease H: a ubiquitous activity in virions of ribonucleic acid tumor viruses. 411 67

A variety of lymphoid cell populations were examined in terms of their ability to replicate vesicular stomatitis virus (VSV), a lytic, RNA-containing virus maturing at the cell surface. The number of cells capable of producing VSV was estimated in terms of infectious centers by the virus plaque assay (VPA), and morphologically by electron microscopy (EM). The lymphoid cells examined in this study included: (a) lymph node cells from delayed hypersensitive guinea pigs stimulated by specific antigen, (b) mouse spleen cells activated by selective bone marrow-derived (B) cell and thymus derived (T) cell mitogens, and (c) cells of human and murine continuous lymphoblastoid or lymphoma lines. In unstimulated cultures of guinea pig lymph node cells there is a background of approximately 1 in 1,000 cells which produces VSV; in purified protein derivative (PPD)-stimulated cultures the number of cells producing virus was 1.6% in the VPA and 1.9% by EM. These cells were large lymphocytes with some morphological features of transformed lymphocytes but were not typical blast cells. A few macrophages were associated with virus in both stimulated and control cultures. These observations indicate that (a) cells responsive to antigens, as detected by a marker virus, were lymphocytes; (b) cells other than lymphocytes (macrophages) were capable of replicating VSV even without antigenic stimulation; and (c) the correlation of results obtained by VPA and morphologic examination was usually quite good. Of the total number of mouse spleen cells stimulated with concanavalin (Con A), a T cell mitogen, 4.5 (EM)-5.7% (VPA) were associated with VSV. These were characteristic transformed lymphocytes, similar to phytohemagglutinin (PHA)-stimulated human lymphocytes. In contrast Escherichia coli lipopolysaccharide (LPS)-treated mouse spleen cultures contained lower numbers of virus plaque-forming cells. The majority of such cells associated with virus displayed extensive rough endoplasmic reticulum. Two cultured murine lymphomas containing lymphocytes with the theta surface marker (L5178Y and EL-4) showed a 15-100-fold higher incidence of virus-producing cells than leukemias (L1210 and C57Bl/6) which did not carry this marker. Similarly, the L2C guinea pig leukemia, a known B cell leukemia, yielded a low percent of virus plaque-forming cells (<2%). However, MOPC-104, a plasma cell tumor presumed to be of B cell origin, was found to be an efficient virus producer. There was a wide variation in the efficiency of VSV replication among human lymphoblastoid lines. One line, Wil-2, produced 80% infectious centers after 24 h of exposure to VSV, and all cells were associated with virus at the EM level. The relationship between the virus-producing cells and different lymphocyte subpopulations as well as the efficiency of the two assays for studying virus-producing lymphocytes is discussed.
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PMID:The production of vesicular stomatitis virus by antigen- or mitogen-stimulated lymphocytes and continuous lymphoblastoid lines. 434 76

This is a report of a 24-year follow-up of a man now 33 years of age, who suffers almost continuously from severe inflammatory lesions of the lips, nose and eyelids, with increased susceptibility to respiratory infections since early childhood. The condition, previously described as "pyo-rhino-blepharo-stomatitis vegetans (McCarthy)", was treated with systemic corticosteroids and antimicrobial agents for years, but failed to improve until the immune status of the patient was checked after withdrawal of the steroids. T lymphocytes were found to be abnormal as to count in peripheral blood and various functional qualities determined in vivo and in vitro. For treatment, levamisole and thymopoietin pentapeptide (TP-5) were given. Subsequently each drug induced rapid and complete clearing of all lesions, but was followed by the recurrence of facial periorificial lesions after drug withdrawal. Change of the regimen by administering either inosiplex orally or commercial calf thymus extract parenterally, remained ineffective. During therapy with levamisole as well as TP-5, the number of T lymphocytes in peripheral blood normalized, yet impaired functions failed to improve. There was an elevated ratio of T-suppressor/T-inducer cells in blood using OKT antibodies. In vitro testing of different functions of polymorphonuclear leucocytes revealed normal results except for a slight decrease of chemotactic activity during levamisole. In view of the long clinical course, the mass of clinical and immunological data collected over decades, and the therapeutic results as a whole, the disease can be characterized as a peculiar type of pluriorificial pyoderma vegetans, caused by a distinct immunodeficiency of T lymphocytes.
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PMID:[Pyoderma vegetans of facial orifices in T-cell immunodeficiency]. 660 52

Nine foals with combined immunodeficiency were given hepatic and thymus cells from 68- to 110-day-old (gestational age) fetuses or peripheral blood lymphocytes from nonrelated horses. Clinical signs and lesions consistent with graft vs host reaction were observed in eight of the foals. Diarrhea was observed in these 8 foals, and ulcerative dermatitis, stomatitis, or glossitis was detected in 6 of the 8 foals. Histopathologic changes consisting of necrosis and lymphocyte infiltration were observed in liver, skin, alimentary tract, and less frequently in lymphoid tissues. Changes in complete blood counts, plasma bilirubin concentration, and serum sorbitol dehydrogenase activity were compared with sequential histopathologic alterations in the liver of two combined immunodeficiency foals given peripheral blood lymphocytes from unrelated donor horses. Elevations of sorbitol dehydrogenase correlated with the onset and increasing severity of hepatic lesions.
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PMID:Graft versus host reactions in foals with combined immunodeficiency. 698 99

We examined T cell development and T cell repertoire in transgenic mice expressing a single T cell receptor (TCR) alpha chain derived from the H-2Db-lymphocytic choriomeningitis virus (LCMV)-specific cytolytic T lymphocyte (CTL) clone P14. To generate these alpha P14 mice, mice transgenic for the P14 TCR alpha chain were backcrossed to TCR alpha-deficient mice. Thymi from alpha P14 mice exhibited a marked decrease of mature CD4+8- and CD8+4- single-positive thymocytes comparable to thymi from TCR alpha-deficient mice. Correspondingly, the number of peripheral T cells was reduced in the CD4 (tenfold) and in the CD8 (twofold) subsets when compared to normal mice. T cells from alpha P14 mice generated a primary anti-LCMV CTL response when stimulated in vitro with LCMV in contrast to normal mice which require priming in vivo; elimination of LCMV in vivo was, however, not improved. Flow cytometric analysis of T cells with V beta-specific antibodies showed a diverse endogenous TCR V beta repertoire. Functional analysis of the T cell repertoire, however, revealed a strongly reduced (30-fold) allogeneic and the absence of a vesicular stomatitis virus-specific CTL response and an impaired ability to provide T cell help for antibody isotype switching. Thus, T cell selection in the thymus was impaired and the T cell repertoire was limited in mice expressing only one type of TCR alpha chain.
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PMID:T cell development and repertoire of mice expressing a single T cell receptor alpha chain. 758 40


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