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Antonina Accardo-Palumbo Anna Rita Giardina Francesco Ciccia Angelo Ferrante Alfonso Principato Rosalia Impastato Ennio Giardina Giovanni Triolo 《Arthritis research & therapy》2010,12(3):R109
Introduction
Infliximab is a chimeric monoclonal antibody against tumor necrosis factor alpha (TNF-α) that has been introduced recently for Behçet's disease (BD) patients who were resistant to standard treatment. The aim of this study was to analyse the functional changes of Vγ9/Vδ2 T lymphocytes in both active and inactive disease and the effect of infliximab on Vγ9/Vδ2 T cell expansion, activation and cytotoxicity.Methods
We investigated 1) cell expansion, 2) expression of TNFRII receptor, 3) perforin and gamma interferon (IFN) content, 4) release of granzyme A (GrA) and 5) phenotype changes, in vitro and in vivo, in Vγ9/Vδ2 T lymphocytes by means of fluorescence-activated cell sorter analysis of lymphocyte cultures from patients with active and inactive BD and healthy subjects.Results
Cell expansion, expression of TNFRII, perforin and gamma IFN content and release of granzyme A were significantly higher in active patients. In vitro and ex vivo treatment with infliximab resulted in a significant reduction of all parameters together with changes in the phenotype of Vγ9/Vδ2 T cells.Conclusions
All together these data indicate that infliximab is capable of interfering with Vγ9/Vδ2 T cell function in BD and although cell culture models cannot reliably predict all potential effects of the drug in vivo, our results present the possibility that this drug may find use in a range of immunological disorders, characterized by dysregulated cell-mediated immunity.3.
Maturation as well as antigen-dependent activation of B cells is accompanied by alternating phases of proliferation and quiescence. We and others have previously shown that Krüppel-like factor 2 (KLF2), a regulator of T cell quiescence and migration, is upregulated in small resting precursor (pre)-B cells after assembly of the immature pre-B cell receptor (pre-BCR) and is downregulated upon antigen-induced proliferation of mature B cells. These findings suggest that KLF2, besides its function in maintaining follicular B cell identity, peripheral B cell homeostasis and homing of antigen-specific plasma cells to the bone marrow, also controls clonal expansion phases in the B cell lineage. Here, we demonstrate that enforced expression of KLF2 in primary pre-B cells results in a severe block of pre-BCR-induced proliferation, upregulation of the cell cycle inhibitors p21 and p27 and downregulation of c-myc. Furthermore, retroviral KLF2 transduction of primary B cells impairs LPS-induced activation, favors apoptosis and results in reduced abundance of factors, such as AID, IRF4 and BLIMP1, that control the antigen-dependent phase of B cell activation and plasma cell differentiation. Hence, we conclude that KLF2 is not only a key player in terminating pre-B cell clonal expansion but also a potent suppressor of B cell activation. 相似文献
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Eleonora Cimini Chiara Agrati Gianpiero D’Offizi Chrysoula Vlassi Rita Casetti Alessandra Sacchi Raffaella Lionetti Veronica Bordoni Nicola Tumino Paola Scognamiglio Federico Martini 《PloS one》2015,10(6)
Gut-associated immune system has been identified as a major battlefield during the early phases of HIV infection. γδ T-cells, deeply affected in number and function after HIV infection, are able to act as a first line of defence against invading pathogens by producing antiviral soluble factors and by killing infected cells. Despite the relevant role in mucosal immunity, few data are available on gut-associated γδ T-cells during HIV infection. Aim of this work was to evaluate how primary (P-HIV) and chronic (C-HIV) HIV infection affects differentiation profile and functionality of circulating and gut-associated Vδ1 and Vδ2 T-cells. In particular, circulating and mucosal cells were isolated from respectively whole blood and residual gut samples from HIV-infected subjects with primary and chronic infection and from healthy donors (HD). Differentiation profile and functionality were analyzed by multiparametric flow cytometry. P-HIV and C-HIV were characterized by an increase in the frequency of effector Vδ1-T cells both in circulating and mucosal compartments. Moreover, during P-HIV mucosal Vδ1 T-cells expressed high levels of CD107a, suggesting a good effector cytotoxic capability of these cells in the early phase of infection that was lost in C-HIV. P-HIV induced an increase in circulating effector Vδ2 T-cells in comparison to C-HIV and HD. Notably, P-HIV as well as HD were characterized by the ability of mucosal Vδ2 T-cells to spontaneously produce IFN-γ that was lost in C-HIV. Altogether, our data showed for the first time a functional capability of mucosal Vδ1 and Vδ2 T-cells during P-HIV that was lost in C-HIV, suggesting exhaustion mechanisms induced by persistent stimulation. 相似文献
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Abstract
Temporal analyses of cell division and tissue expansion in pea, tobacco, and sunflower leaves reveal that both processes follow
similar patterns during leaf development. Relative cell division and relative tissue expansion rates are maximal and constant
during early leaf development, but they decline later. In contrast, relative cell expansion rate follows a bell-shaped curve
during leaf growth. Cell division and tissue expansion have common responses to temperature, intercepted radiation, and water
deficit. As a consequence, final leaf area and cell number remain highly correlated throughout a large range of environmental
conditions for these different plant species, indicating that cell division and tissue expansion are co-ordinated during leaf
development. This co-ordination between processes has long been explained by dependence between both processes. Most studies
on dicotyledonous leaf development indicate that leaf expansion rate depends on the number of cells in the leaf. We tested
this hypothesis with a large range of environmental conditions and different plant species. Accordingly, we found a strong
correlation between both absolute leaf expansion rate and leaf cell number. However, we showed that this relationship is not
necessarily causal because it can be simulated by the hypothesis of independence between cell division and tissue expansion
according to Green's theory of growth (1976).
Received 23 February 2000; accepted 3 March 2000 相似文献
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《Cell metabolism》2014,19(1):122-134
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Chemotherapy and zoledronate sensitize solid tumour cells to Vγ9Vδ2 T cell cytotoxicity 总被引:1,自引:0,他引:1
Combinations of cellular immune-based therapies with chemotherapy and other antitumour agents may be of significant clinical
benefit in the treatment of many forms of cancer. Gamma delta (γδ) T cells are of particular interest for use in such combined
therapies due to their potent antitumour cytotoxicity and relative ease of generation in vitro. Here, we demonstrate high
levels of cytotoxicity against solid tumour-derived cell lines with combination treatment utilizing Vγ9Vδ2 T cells, chemotherapeutic
agents and the bisphosphonate, zoledronate. Pre-treatment with low concentrations of chemotherapeutic agents or zoledronate
sensitized tumour cells to rapid killing by Vγ9Vδ2 T cells with levels of cytotoxicity approaching 90%. In addition, zoledronate
enhanced the chemotherapy-induced sensitization of tumour cells to Vγ9Vδ2 T cell cytotoxicity resulting in almost 100% lysis
of tumour targets in some cases. Vγ9Vδ2 T cell cytotoxicity was mediated by perforin following TCR-dependent and isoprenoid-mediated
recognition of tumour cells. Production of IFN-γ by Vγ9Vδ2 T cells was also induced after exposure to sensitized targets.
We conclude that administration of Vγ9Vδ2 T cells at suitable intervals after chemotherapy and zoledronate may substantially
increase antitumour activities in a range of malignancies.
Financial
support and conflicts of interest: This study was supported by grants from Medinet (Japan), and Suncorp Metway and Gallipoli Research Foundation (Australia).
No financial or commercial interests arise from this study. Informed consent: This study was approved by Human Research Ethics Committees of the University of Queensland and Greenslopes Private Hospital
and informed consent was obtained from all subjects. 相似文献
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Gertner-Dardenne J Castellano R Mamessier E Garbit S Kochbati E Etienne A Charbonnier A Collette Y Vey N Olive D 《Journal of immunology (Baltimore, Md. : 1950)》2012,188(9):4701-4708
Vγ9Vδ2 T cells are attractive candidates for antileukemic activity. The analysis of Vγ9Vδ2 T cells in newly diagnosed acute myeloid leukemia (AML) patients revealed that their absolute cell numbers were normal in the blood as well as in the bone marrow but showed a striking imbalance in the differentiation subsets, with preponderance of the effector memory population. This unusual phenotype was restored after removal of leukemic cells in patients, which reached complete remission after chemotherapy, suggesting that leukemic cells might be involved in the alteration of γδ T cell development in AML. Accordingly, coculture between AML cells and Vγ9Vδ2 T cells induced selection of effector cells. In accordance with their effector memory status, in vitro proliferation of Vγ9Vδ2 T cells was reduced compared with normal controls. Nevertheless, Vγ9Vδ2 T cells efficiently killed autologous AML blasts via the perforin/granzyme pathway. The ligands for DNAM-1 were expressed by AML cells. We showed that killing of AML blasts was TCR and DNAM-1 dependent. Using a xenotransplantation murine model, we showed that Vγ9Vδ2 T cells homed to the bone marrow in close proximity of engrafted leukemic cells and enhanced survival. These data demonstrate that Vγ9Vδ2 T cells are endowed with the ability to interact with and eradicate AML blasts both in vitro and in a mouse model. Collectively, our data revealed that Vγ9Vδ2 T cells have a potent antileukemic activity provided that optimal activation is achieved, such as with synthetic TCR agonists. This study enhances the interest of these cells for therapeutic purposes such as AML treatment. 相似文献
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The structural stability, elastic properties, anisotropy, dynamics stability and thermodynamics properties were explored for pure Al and HoT2Al20 intermetallics from the first-principles method. The formation enthalpy and phonon frequencies indicate that these HoT2Al20 intermetallics maintain structural stability. The elastic constants Cijs and moduli B, G, E and Hv indicate these intermetallics possess higher hardness and the better resistance to deformation. The values of Poisson’s ratio and B/G demonstrate that HoT2Al20 intermetallics are brittle materials. The anisotropic constants and anisotropic acoustic velocities confirm that HoT2Al20 intermetallics exhibit anisotropic properties. Importantly, the calculated thermal quantities demonstrate that these new HoT2Al20 intermetallics possess the better thermodynamic properties at high temperature. 相似文献
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Katsuhiko Omoe Wataru Nunomura Hidehito Kato Zhong-Juan Li Osamu Igarashi Minako Araake Keigo Sano Hisaya K. Ono Yohei Abe Dong-Liang Hu Akio Nakane Hiroshi Kiyono Yuichi Takakuwa Kunihiro Shinagawa Takehiko Uchiyama Ken'ichi Imanishi 《The Journal of biological chemistry》2010,285(40):30427-30435
In mice implanted with an osmotic pump filled with the superantigen (SAG) staphylococcal enterotoxin A (SEA), the Vβ3+CD4+ T cells exhibited a high level of expansion whereas the Vβ11+CD4+ T cells exhibited a mild level of expansion. In contrast, in mice implanted with an osmotic pump filled with SE-like type P (SElP, 78.1% homologous with SEA), the Vβ11+CD4+ T cells exhibited a high level of expansion while the Vβ3+CD4+ T cells exhibited a low level of expansion, suggesting that the level of the SAG-induced response is determined by the affinities between the TCR Vβ molecules and SAG. Analyses using several hybrids of SEA and SElP showed that residue 206 of SEA determines the response levels of Vβ3+CD4+ and Vβ11+CD4+ T cells both in vitro and in vivo. Analyses using the above-mentioned hybrids showed that the binding affinities between SEA and the Vβ3/Vβ11 β chains and between SEA-MHC class II-molecule complex and Vβ3+/Vβ11+ CD4+ T cells determines the response levels of the SAG-reactive T cells both in vitro and in vivo. 相似文献
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Andrea M. Powell W.Y. Chan Patrick Alvin Iris F. Litt 《Prostaglandins & other lipid mediators》1985,29(2):273-289
Although it has been demonstrated that primary dysmenorrhea is associated with elevated levels of PGF2α in the menstrual fluid, little is actually known of the menstrual-PG profiles of either dysmenorrheic or normal women. In this study, menstrual fluid from normal and dysmenorrheic women was collected from tampons and extracted for PG-like substances. The PGF2α, PGE2 and TXA2 content was analyzed by RIA.This study demonstrates that dysmenorrheics have significantly higher levels/concentrations of menstrual-PGF2α and PGe2 than do normal women, and that there is no difference in the menstrual-PGF2α: PGE2 ratio between the two groups. Also, there is no significant difference in the amount/concentration of menstrual-thromboxane between dysmenorrheic and normal women. Of the parameters considered, the levels/-concentrations of menstrual-PGF2α, PGE2 and TXA2, dysmenorrheic pain correlates best with the rate of menstrual-PGF2α release. 相似文献
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Cyclooxygenase-2 (COX-2) activity has been implicated in the pathogenesis of cerebral ischemia. To determine whether COX-2
activity within the neuron itself exacerbates hypoxic neuronal injury, neuron-enriched cultures were subjected to anoxia.
Treatment with COX-2 selective antagonists decreased cell death. Neurons cultured from homozygous COX-2 gene disrupted mice
were resistant to hypoxia compared to those of heterozygotes. Infection of primary neurons with AAV expressing COX-2 exacerbated
cell death compared to neurons infected with enhanced green fluorescent protein (EGFP) control vector. Addition of PGE2, PGD2
or PGF2α to the medium exacerbated injury, suggesting that the deleterious effects of COX-2 overexpression in hypoxia could
be mediated by direct receptor mediated effects of prostaglandins. Overexpression of COX-2 did not increase expression of
cyclin D1 or phosphoretinoblastoma protein (pRb), or cleavage of caspase 3 suggesting that this cell cycle mechanism does
not mediate COX-2 toxicity in this model. 相似文献
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Keith R. Barnard Robert W. Gable A. G. Wedd 《Journal of biological inorganic chemistry》1997,2(5):623-633
Synthesis of complexes cis,cis-WVOXL (X=Cl, NCS), cis,trans-WVOXL (X=Cl, OPh, SPh) and cis,trans-WVIE2L (E2=O2, OS, S2) of the title ligand LH2 are reported. cis,cis-WVOCIL crystallises in space group P21/c with a=13.6541(9) Å, b=7.1555(11) Å, c=18.198(2) Å, β=95.294(6)°, V=1770.4(3) Å3 and Z=4 while the cis,trans isomer crystallises in space group P21/n with a=10.361(3) Å, b=14.141(4) Å, c=12.213(5) Å, β=102.56(3)°, V=1747(2) Å3 and Z=4. cis,trans-WVIS2L crystallises in space group P21/n with a=10.645(2) Å, b=13.929(2) Å, c=12.189(2) Å, β=103.14(2)°, V=1760(1) Å3 and Z=4. A short CH3···Cl distance of 3.067(7) Å and an acute OWCl angle of 94.1(2)° are seen in cis,cis-WVOClL, which converts to the cis,trans form on heating in MeCN. The latter isomer features a CH3···Cl distance of 3.38(2) Å and an OWCl angle of 105.1(8)°. Electrochemical and EPR data are reported. In particular, cis,trans-WVIE2L may be reduced to [WVE2L]–. EPR properties of these anions and those of complexes WVOXL are discussed in the context of WV centres in tungsten enzymes. 相似文献
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The Auxin-Binding Protein 1 (ABP1) was identified over 30 years ago thanks to it''s high affinity for active auxins. ABP1 plays an essential role in plant life yet to this day, its function remains ‘enigmatic.’ A recent study by our laboratory shows that ABP1 is critical for regulation of the cell cycle, acting both in G1 and at the G2/M transition. We showed that ABP1 is likely to mediate the permissive auxin signal for entry into the cell cycle. These data were obtained by studying a conditional functional knock-out of ABP1 generated by cellular immunization in the model tobacco cell line, Bright Yellow 2.Key Words: auxin responses, auxin-binding protein 1, immunomodulation, cellular immunisation 相似文献
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David W. Wright Richard T. Chang Sanjay K. Mandal W. H. Armstrong William H. Orme-Johnson 《Journal of biological inorganic chemistry》1996,1(2):143-151
Initial investigations into the possible roles of homocitric acid in the biosynthesis and function of the active site cofactor of nitrogenase resulted in the isolation and characterization of the dinuclear vanadium(V) species [K2(H2O)5][(VO2)2(R,S-C7H8O7)2]·H2O ( 1). Complex 1 represents the first synthetic structurally characterized transition metal homocitrate complex and may represent an early mobilized precursor in the biosynthesis of VFeco. Compound 1 was characterized by a variety of physical methods, including X-ray crystallography. Crystal data: space group P?* (#2), with a?=?10.292 (3)?Å, b?=?16.663 (3)?Å, c?=?8.343 (1)?Å, α?=?95.93 (1)°, β?=?105.74 (2)°, γ?=?90.86 (2)°, V?=?1386 (1)?Å3, and Z?=?2. The homocitrate ligand is coordinated to the vanadium(V) atoms in a bidentate fashion via the deprotonated bridging hydroxyl group and a carboxylate donor. This unique coordination mode accurately mimics the coordination of homocitrate to the cofactor of nitrogenase. 相似文献
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Rajamanickam Anuradha Parakkal Jovvian George Luke E. Hanna Vedachalam Chandrasekaran P. Paul Kumaran Thomas B. Nutman Subash Babu 《PLoS neglected tropical diseases》2014,8(1)