| 1. |
- Simark-Mattsson, Charlotte, 1955, et al.
(författare)
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T cell receptor V-gene usage in oral lichen planus; increased frequency of T cell receptors expressing V alpha 2 and V beta 3.
- 1994
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Ingår i: Clinical and experimental immunology. - 0009-9104. ; 98:3, s. 503-7
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Tidskriftsartikel (refereegranskat)abstract
- In order to analyse the clonality of T cells in the inflammatory infiltrate of oral lichen planus (OLP), mucosal biopsies were obtained from seven patients with manifest disease. The biopsies were stained with MoAbs directed against 11 different T cell receptor (TCR) V-gene families, anti-CD4, anti-CD8 and IL-2 receptor (IL-2R). For comparison, the frequencies of the different TCR V-families were determined in biopsies from five patients with oral candidosis as well as in peripheral blood from three patients with OLP and from six healthy blood donors (HBD). The occurrence of the investigated TCR V-families varied between 0% and 7% in venous blood obtained from both HBD and OLP patients. T lymphocytes expressing the TCR V beta 3 and V alpha 2 in OLP biopsies were, however, detected in frequencies ranging between 18% and 40% of the total fraction of lymphocytes, a consistent finding for all the OLP infiltrates studied. The other nine TCR V-families examined appeared in low frequencies both in biopsies and in peripheral blood. V alpha 2+ and V beta 3+ cells were often localized adjacent to the basal membrane. In contrast, T cells in Candida-induced lesions did not express a biased TCR distribution, and most V-families studied appeared in frequencies of 0-6%. Thus, T lymphocytes in OLP lesions express a substantially higher frequency of TCR V alpha 2 and V beta 3 than expected from the distribution in blood. The clonal expansion of T cells observed in OLP suggests that a superantigen is involved in the pathogenesis of the disease. Whether this superantigen is of exogenous or endogenous origin needs to be investigated.
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| 2. |
- Adlesic, M., et al.
(författare)
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Histamine in rheumatoid arthritis
- 2007
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Ingår i: Scand J Immunol. - : Wiley. - 0300-9475 .- 1365-3083. ; 65:6, s. 530-7
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is an autoimmune disease characterized by a persistent inflammation of the synovium, leading to the erosion of articular cartilage and bone. Synovial mast cells and their effector molecule, histamine, receive increased attention as mediators of joint inflammation. The aim of our study was to analyse levels of free histamine in serum and joint fluid of RA patients and to evaluate the potential inflammatogenic properties of histamine in vivo and in vitro. Histamine levels were measured by an ELISA in synovial fluid and sera of RA patients and of healthy controls. Histamine levels were also assessed in plasma of RA patients undergoing anti-TNF-alpha treatment. In the murine part of the study, histamine was injected intra-articularly in the knee joint of mice and the joints were subsequently analysed with respect to induction of inflammation. RA patients displayed significantly lower levels of histamine in circulation (0.93 +/- 0.16 ng/ml) compared with the healthy controls (1.89 +/- 0.45 ng/ml, P < 0.001). Locally, in synovial fluid the levels of histamine were even lower (0.37 +/- 0.16 ng/ml, P < 0.0006). Long-term anti-TNF-alpha treatment significantly increased circulating levels of histamine in RA patients. Our experiments on animals show that histamine on its own neither induces inflammation in the joint cavity nor influences the course of HMGB1 and peptidoglycan-induced joint inflammation. Based on our experimental and clinical studies we suggest that histamine lacks harmful properties in RA.
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| 3. |
- Amu, Sylvie, 1978, et al.
(författare)
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B-cell CD25 expression in murine primary and secondary lymphoid tissue
- 2006
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Ingår i: Scand J Immunol. - : Wiley. - 0300-9475. ; 64:5, s. 482-92
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Tidskriftsartikel (refereegranskat)abstract
- B cells are in analogy with T cells capable of expressing functional IL-2 receptors. IL-2R alpha-chain (CD25) positive T cells have been studied in detail but not much is known about CD25 positive B cells. The aim of this study was to examine the phenotypic properties of the CD25 expressing B cells collected from different lymphoid organs in mice. Samples were stained for various cell surface markers and analysed using flow cytometry. We found that approximately 49% of B cells in bone marrow, 16% in peritoneal cavity, 2% in spleen and 1% in lymph nodes express CD25. In contrast, CD25 expressing B cells were not found in the blood or in Peyer's patches. Phenotypic characterization showed that CD25+ B cells in spleen, lymph nodes and peritoneal cavity have higher expression of AA4.1, CD5, CD69, CD80, CD86, CD122, CD132, IgA, IgG and IgM on their surface in comparison with CD25- B cells. In contrast, expression of IgD and IA-IE was lower on CD25+ B cells in spleen and lymph nodes. In bone marrow, the expression of CD5, CD80, CD86, CD122, CD132, IgA, IgD and IgM was lower, while the expression of AA4.1, IgG and IA-IE was increased on CD25+ B cells compared with CD25- B cells. In conclusion, our results indicate that B cells expressing CD25 are phenotypically distinctly different from those that are CD25 negative. Our findings suggest that CD25+ B cells are more prone to efficient antigen presentation and display a more mature phenotype.
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| 4. |
- Amu, Sylvie, 1978, et al.
(författare)
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CD25-expressing B-lymphocytes in rheumatic diseases
- 2007
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Ingår i: Scand J Immunol. - : Wiley. - 0300-9475. ; 65:2, s. 182-91
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Tidskriftsartikel (refereegranskat)abstract
- B cells play an important role in the development of autoimmune diseases due to their production of autoantibodies, antigen-presenting capacity and production of pro-inflammatory cytokines. The purpose of the present study was to analyse B cells from rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients, with respect to their expression of the IL-2 receptor (IL-2R) subunit CD25. Using flow cytometry, we found that CD25(+) B cells from RA patients expressed significantly higher frequencies of CD122 and CD132 than CD25(+) B cells from control subjects, indicating a fully functional IL-2R. These CD25(+) B cells also expressed higher frequencies of the co-stimulatory molecule CD80, whereas IgM and IgA expression was decreased compared with CD25(+) B cells from healthy controls. In addition B cells from SLE patients co-expressed CD25 together with CD80, CD122, and CD132, but to a lower degree IgD and IgM, when compared with healthy controls. Taken together, our results indicate that CD25(+) B cells from RA and SLE patients are in a highly activated state, display a more mature phenotype and suggest that this B cell subset may be involved in the pathogenesis of RA and SLE.
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| 5. |
- Amu, Sylvie, 1978, et al.
(författare)
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The Human Immunomodulatory CD25(+) B Cell Population belongs to the Memory B Cell Pool
- 2007
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Ingår i: Scand J Immunol. - 0300-9475. ; 66:1, s. 77-86
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Tidskriftsartikel (refereegranskat)abstract
- We have shown that human CD20(+)25(+) B cells display immunomodulatory properties. The aim of this study was to investigate if CD25(+) B cells are found within the CD27 memory B cell population, and to analyse pattern of their cytokine production. B cells isolated from healthy subjects, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients were analysed regarding the frequency of CD25(+) B cells within certain B cell subsets. Purified CD25(+) B cells from healthy subject were used in vitro to evaluate their production of immunomodulatory cytokines. In healthy subjects the majority (60%) of memory B cells (CD20(+)27(+)) also co-expressed CD25 while only 10-20% of the naive B cells (CD20(+)27(-)) and plasmablasts (CD20-27(+)) expressed CD25. In RA and SLE patients, we found that 51% and 48%, respectively, co-expressed CD25 in the memory population, whereas only 11% and 9% co-expressed CD25 in the naive B cell population. Phenotypic analysis of the CD20(+)25(+)27(+) and CD20(+)25(+)27(-) cells using CD10, CD24, CD38, CD45, CD71, CD80, CD86, CD95, CD138, BAFF-R, TACI, IgA, IgD, IgG and IgM showed that CD20(+)25(+)27(+) B cells preferentially represent highly activated, Ig class switched memory B cells. Cytokine profile analysis showed that CD25(+) B cells secreted significantly higher levels of IL-10 versus CD25(-) B cells. In contrast, TGF-beta1 secretion was similar between the CD25(+) and CD25(-) sub-populations. In conclusion, CD20(+)25(+) B cells constitute a unique subpopulation preferentially occurring among CD20(+)27(+) memory B cells. We suggest that CD25 can be used as a marker for a memory B cell subset.
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| 6. |
- Antosiewicz, Tomasz, 1981, et al.
(författare)
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Localized Surface Plasmon Decay Pathways in Disordered Two-Dimensional Nanoparticle Arrays
- 2015
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Ingår i: ACS Photonics. - : American Chemical Society (ACS). - 2330-4022. ; 2:12, s. 1732-1738
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Tidskriftsartikel (refereegranskat)abstract
- The size and shape of a metal nanoparticle determine its optical properties. When placed in an array the single particle response is further modified by the scattered fields, which for a random array are unique to each scatterer. However, at the array level scattering and absorption retain single-particle-like spectra. Using T-Matrix calculations and an analytical model of intra-array coupling in amorphous arrays we show how the branching ratio of the localized plasmon decay depends on disorder and particle density. We calculate the effective polarizability and demonstrate its effects on scattering and absorption. The scattering-to-absorption ratio is a function of particle separation in the disordered array and can significantly deviate from the inherent single particle ratio. We trace the period of this oscillatory dependence of the ratio to the single particle plasmon resonance wavelength. This effect has implications for applications in which one of the decay channels has to be dominant, for example, absorption for hot electron hole pair generation in the metal particles or scattering into a nearby semiconductor.
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| 7. |
- Baran, M, et al.
(författare)
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SURVIVIN IS AN ESSENTIAL MEDIATOR OF ARTHRITIS INTERACTING WITH UROKINASE SIGNALLING.
- 2009
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Ingår i: Journal of cellular and molecular medicine. - : Wiley. - 1582-4934 .- 1582-1838. ; 13:9B, s. 3797-3808
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT Proto-oncogene survivin has recently been identified as a prognostic marker distinguishing patients with destructive rheumatoid arthritis (RA). In the present material of 132 RA patients and 82 controls the levels of survivin correlated to urokinase (uPA) (r=0.46), a plasminogen activator over expressed in inflamed joints and known to exhibit potent arthritogenic properties. Here we evaluate the functional relationship between these proteins using primary synovial fibroblasts and leukocytes of RA patients, human monocytic (THP-1) and fibroblast (MRC-5) cell lines. Using inhibitors of intracellular signalling we show that uPA and survivin share common transduction pathways being in synovial fibroblasts dependent on the activity of tyrosine kinases, PI3-kinase and MEK. Moreover, uPA production is significantly reduced in fibroblasts if survivin synthesis has been silenced by siRNA. Importantly, silencing of survivin in fibroblasts prevented their invasive growth in knee joints of SCID mice. Interaction of uPA with receptor up regulates survivin expression in leukocytes. In turn, survivin is required for the upregulation of uPA receptor on cell surface. These findings indicate that survivin is an essential mediator of arthritogenic properties of uPA regulating its synthesis in synovial fibroblasts and uPAR expression in leukocytes. Close correlation between survivin and uPA levels in patients with RA supports the importance of this connection for the pathogenesis of arthritis.
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| 8. |
- Bian, Li, et al.
(författare)
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Dichloroacetate alleviates development of collagen II-induced arthritis in female DBA/1 mice
- 2009
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Ingår i: ARTHRITIS RESEARCH and THERAPY. - : BioMed Central. - 1478-6354 .- 1478-6362. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Dichloroacetate (DCA) has been in clinical use for the treatment of lactacidosis and inherited mitochondrial disorders. It has potent anti-tumor effects both in vivo and in vitro, facilitating apoptosis and inhibiting proliferation. The proapoptotic and anti-proliferative properties of DCA prompted us to investigate the effects of this compound in arthritis. Methods In the present study, we used DCA to treat murine collagen type II (CII)-induced arthritis (CIA), an experimental model of rheumatoid arthritis. DBA/1 mice were treated with DCA given in drinking water. Results Mice treated with DCA displayed much slower onset of CIA and significantly lower severity (P less than 0.0001) and much lower frequency (36% in DCA group vs. 86% in control group) of arthritis. Also, cartilage and joint destruction was significantly decreased following DCA treatment (P = 0.005). Moreover, DCA prevented arthritis-induced cortical bone mineral loss. This clinical picture was also reflected by lower levels of anti-CII antibodies in DCA-treated versus control mice, indicating that DCA affected the humoral response. In contrast, DCA had no effect on T cell-or granulocyte-mediated responses. The beneficial effect of DCA was present in female DBA/1 mice only. This was due in part to the effect of estrogen, since ovariectomized mice did not benefit from DCA treatment to the same extent as sham-operated controls (day 30, 38.7% of ovarectomized mice had arthritis vs. only 3.4% in sham-operated group). Conclusion Our results indicate that DCA delays the onset and alleviates the progression of CIA in an estrogen-dependent manner.
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| 9. |
- Bjersing, Jan, 1966, et al.
(författare)
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Anti-proliferative effects of phosphodiester oligodeoxynucleotides
- 2004
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Ingår i: Immunobiology. - : Elsevier BV. - 0171-2985. ; 209:8, s. 637-45
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Tidskriftsartikel (refereegranskat)abstract
- The immunostimulatory effects of cytosine-phosphate-guanosine (CpG)-containing oligodeoxynucleotides (ODNs) have been extensively documented. In this paper, we describe the inhibitory effects of ODNs that contain natural phosphodiester backbones (O-ODNs) on the immunostimulation caused by CpG-containing phosphorothioated ODNs (CpG-S). CpG-S stimulation of mouse splenocyte proliferation was reduced by the addition of O-ODNs that contained or lacked the CpG-motif (CpG-containing phosphodiester oligodeoxynucleotide, CpG-O or GpC-O). The total number of cultured splenocytes was up-regulated by CpG-S, whereas repetitive addition of O-ODNs to the cell cultures inhibited this effect. The frequency of T2-like B cells was found to be increased by CpG-S. The culture supernatants of CpG-S-treated splenocytes contained elevated levels of IL-10 and IL-6. However, IL-10 and IL-6 production was down-regulated significantly by the combination of CpG-S and either CpG-O or GpC-O. The O-ODN mediated inhibition of proliferation was less pronounced in IL-10-/- mice. Thus, the O-ODNs, irrespective of CpG content, exerted inhibitory activities on the proliferation of B cells. These anti-proliferative effects appear to be mediated both by the down-regulation of IL-10 production and increased apoptosis.
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| 10. |
- Bjersing, Jan, 1966, et al.
(författare)
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Impact of site-specific nucleobase deletions on the arthritogenicity of DNA
- 2004
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Ingår i: Inflammation. - 0360-3997. ; 28:3, s. 159-68
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Tidskriftsartikel (refereegranskat)abstract
- Oligodeoxynucleotides (ODN) containing unmethylated CpG motifs (CpG ODN) potently stimulate the innate and acquired immune system. We have compared the in vivo and in vitro inflammatogenic properties of CpG ODNs containing a specific nucleobase deletion either 5'-upstream (ODN-2) or 3'-downstream (ODN-3) of the CpG motif, comparing with a prototype CpG ODN (ODN-1). The frequency of arthritis was similar after intra-articular (i.a.) injections of ODN-1 or ODN-3, but was significantly lower (p < 0.02) after i.a. injections of ODN-2. In vitro production of the pro-inflammatory cytokine TNF-alpha was higher in mouse spleen cell cultures exposed to ODN-2 in comparison to ODN-1. In addition, the level of IL-10 induced by ODN-2 was higher than that induced by ODN-1. On the other hand, TNF-alpha, IL-10, and MCP-1 levels, as well as splenocyte proliferative responses were all significantly lower for ODN-3 than for ODN-1. These results suggest that a 5'-upstream nucleobase deletion reduces arthritogenicity, while maintaining or increasing the production of pro- and anti-inflammatory factors. In contrast, a 3'-downstream nucleobase deletion has no effect on arthritogenicity, despite significantly lower levels of proliferation and pro- and anti-inflammatory cytokines, compared with ODN-1. This study indicates that specific structural elements within the ODN sequence but outside the CpG motif, modulate the immunostimulatory properties of CpG ODNs.
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