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101.
OX40-mediated memory T cell generation is TNF receptor-associated factor 2 dependent 总被引:7,自引:0,他引:7
Prell RA Evans DE Thalhofer C Shi T Funatake C Weinberg AD 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(11):5997-6005
Tumor necrosis factor receptor-associated factor 2 (TRAF2), an adapter protein that associates with the cytoplasmic tail of OX40, may play a critical role in OX40-mediated signal transduction. To investigate the in vivo role of TRAF2 in OX40-mediated generation of Ag-specific memory T cells, we bred OVA-specific TCR transgenic mice to TRAF2 dominant-negative (TRAF2 DN) mice. Following Ag stimulation and OX40 engagement of TRAF2 DN T cells in vivo, the number of long-lived OVA-specific T cells and effector T cell function was dramatically reduced when compared with wild-type T cells. We also demonstrate that CTLA-4 is down-regulated following OX40 engagement in vivo and the OX40-specific TRAF2 DN defect was partially overcome by CTLA-4 blockade in vivo. The data provide evidence that TRAF2 is linked to OX40-mediated memory T cell expansion and survival, and point to the down-regulation of CTLA-4 as a possible control element to enhance early T cell expansion through OX40 signaling. 相似文献
102.
Hermann H. Prell 《Molecular & general genetics : MGG》1962,93(3):335-350
Summary The temperate Salmonella phage P22 is inactivated by treatment with nitrous acid. The survivors of such treatment are not unharmed because most of them — depending on the dose applicated — show a decreased probability to lysogenize. The HNO2-induced lysogenization or sublethal damages are 3 to 5 times more frequent than the lethal deaminations at pH 4,62. The influence of pH of HNO2-treatment on the decrease of the lysogenization ability indicates that the damage is induced by deamination of the DNA-bases adenin and cytosin.Treatment of P22 with HNO2 — before or after uv-irradiation — reduces the sector for host reactivable uv-damages. The dependence of this damage on pH during HNO2-treatment is the same as for the decrease of probability for lysogenization. From this it is concluded that both, the decrease of probability of lysogenization, and the reduction of the sector of host reactivable uv-damages in the DNA of P22 depend on the same primary lesion. Only its phenotypic expression may be changed depending on the experimental conditions used.None of the two types for phenotypic expression of the sublethal damage is transmissible to the phage progeny as a mutation. This suggests that the damage is caused by a change in molecular structure (H-bridges ?) of the double stranded phage DNA molecule as a consequence of its deamination, which hinders some structural cooperation between phage and bacterial DNA occuring prior to DNA replication responsible for lysogenization and host reactivation of uv-damages.
Mit 9 Textabbildungen 相似文献
Mit 9 Textabbildungen 相似文献
103.
Priefer UB Aurag J Boesten B Bouhmouch I Defez R Filali-Maltouf A Miklis M Moawad H Mouhsine B Prell J Schlüter A Senatore B 《Journal of biotechnology》2001,91(2-3):223-236
The ultimate objective of PhIMED, in which two European (Germany, Italy) and two Mediterranean (Morocco, Egypt) countries collaborate, is to improve the cultivation of French bean (Phaseolus vulgaris) under arid and semi-arid conditions by analysing and enhancing stress tolerance of the nitrogen fixing rhizobial microsymbionts. Rhizobial strains nodulating P. vulgaris (RP strains) isolated from areas in Morocco frequently subjected to drought were analysed for their salt and pH tolerance and their phylogenetic relationship. Strain RP163, exhibiting high nodulation efficiency and a broad pH tolerance was mutagenised by Tn5 and mutants unable to grow on extreme pH media were isolated. Some of the mutants affected in low pH tolerance were found to be mutated in genes related to cobalmin biosynthesis and in succinate dehydrogenase (sdhA). In a parallel approach, promoters and genes inducible under extreme pH values were identified in Rhizobium leguminosarum bv. viciae VF39, among them gabT, which encodes the GABA transaminase and which is induced under acidic conditions. The same gene is present and similarly regulated in RP163. The actSR gene region was cloned from VF39, sequenced and mutants generated in this region were found to be impaired in growth at low pH, but also under neutral conditions. The Agrobacterium rhizogenes 'promintron' promoter, reported to be activated in stationary phase, was found to be also strongly induced under acidic conditions in rhizobia and it is currently being characterised to construct a system allowing the expression of stress tolerance genes in bacteroids and free-living bacteria. 相似文献
104.
Weinberg AD Rivera MM Prell R Morris A Ramstad T Vetto JT Urba WJ Alvord G Bunce C Shields J 《Journal of immunology (Baltimore, Md. : 1950)》2000,164(4):2160-2169
The OX-40 receptor (OX-40R), a member of the TNFR family, is primarily expressed on activated CD4+ T lymphocytes. Engagement of the OX-40R, with either OX-40 ligand (OX-40L) or an Ab agonist, delivers a strong costimulatory signal to effector T cells. OX-40R+ T cells isolated from inflammatory lesions in the CNS of animals with experimental autoimmune encephalomyelitis are the cells that respond to autoantigen (myelin basic protein) in vivo. We identified OX-40R+ T cells within primary tumors and tumor-invaded lymph nodes of patients with cancer and hypothesized that they are the tumor-Ag-specific T cells. Therefore, we investigated whether engagement of the OX-40R in vivo during tumor priming would enhance a tumor-specific T cell response. Injection of OX-40L:Ig or anti-OX-40R in vivo during tumor priming resulted in a significant improvement in the percentage of tumor-free survivors (20-55%) in four different murine tumors derived from four separate tissues. This anti-OX-40R effect was dose dependent and accentuated tumor-specific T cell memory. The data suggest that engagement of the OX-40R in vivo augments tumor-specific priming by stimulating/expanding the natural repertoire of the host's tumor-specific CD4+ T cells. The identification of OX-40R+ T cells clustered around human tumor cells in vivo suggests that engagement of the OX-40R may be a practical approach for expanding tumor-reactive T cells and thereby a method to improve tumor immunotherapy in patients with cancer. 相似文献
105.
Vera Kozjak-Pavlovic Florian Prell Bernd Thiede Monika Götz Dominik Wosiek Christine Ott Thomas Rudel 《Journal of molecular biology》2014
Oxidative phosphorylation (OXPHOS) in mitochondria takes place at the inner membrane, which folds into numerous cristae. The stability of cristae depends, among other things, on the mitochondrial intermembrane space bridging complex. Its components include inner mitochondrial membrane protein mitofilin and outer membrane protein Sam50. We identified a conserved, uncharacterized protein, C1orf163 [SEL1 repeat containing 1 protein (SELRC1)], as one of the proteins significantly reduced after the knockdown of Sam50 and mitofilin. We show that C1orf163 is a mitochondrial soluble intermembrane space protein. Sam50 depletion affects moderately the import and assembly of C1orf163 into two protein complexes of approximately 60 kDa and 150 kDa. We observe that the knockdown of C1orf163 leads to reduction of levels of proteins belonging to the OXPHOS complexes. The activity of complexes I and IV is reduced in C1orf163-depleted cells, and we observe the strongest defects in the assembly of complex IV. Therefore, we propose C1orf163 to be a novel factor important for the assembly of respiratory chain complexes in human mitochondria and suggest to name it RESA1 (for RESpiratory chain Assembly 1). 相似文献
106.
Bacteria have evolved a wide variety of metabolic strategies to cope with varied environments. Some are specialists and only able to survive in restricted environments; others are generalists and able to cope with diverse environmental conditions. Rhizobia (e.g. Rhizobium, Sinorhizobium, Bradyrhizobium, Mesorhizobium and Azorhizobium species) can survive and compete for nutrients in soil and the plant rhizosphere but can also form a beneficial symbiosis with legumes in a highly specialized plant cell environment. Inside the legume-root nodule, the bacteria (bacteroids) reduce dinitrogen to ammonium, which is secreted to the plant in exchange for a carbon and energy source. A new and challenging aspect of nodule physiology is that nitrogen fixation requires the cycling of amino acids between the bacteroid and plant. This review aims to summarize the metabolic plasticity of rhizobia and the importance of amino acid cycling. 相似文献
107.
108.
109.
It is shown that circular PM2 DNA with two gaps of 13 nucleotides per molecule is degraded by purified recBC enzyme from Escherichia coli to acid-soluble material at a rate which is less than one tenth of the rate of solubilization of linear duplex DNA. Increasing the gap length in the circular DNA to 40-650 nucleotides does not affect the breakdown of the molecules by the recBC enzyme, nor does it change the proportions of the products formed (acid-soluble material, acid-insoluble fragments and non-degraded molecules). On the other hand, terminal gaps in linear duplex DNA produced by limited digestion with either exonuclease III or lambda exonuclease significantly reduce the rate of the degradation by the recBC enzyme, particularly when the gaps exceed 100 nucleotides. The results suggest that the recBC enzyme does not cleave gaps in circular DNA at random positions, but possibly at the junction between single-stranded and duplex DNA or close to it. The degradation of gapped circular DNA by purified recBC enzyme was used to search for an inhibitor of the recBC enzyme in extracts from ultraviolet-irradiated cells. No such inhibitor has been observed but rather a weak stimulatory factor for the solubilization of gapped circular DNA by the recBC enzyme. Thus, the experimental system appears not to be suited as a test in vitro for an ultraviolet-induced inhibitor of the recBC enzyme which has been postulated to be produced in recA+ lexA+ cells of E. coli after ultraviolet irradiation. 相似文献
110.