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1.
Bayrak S; Holmdahl R; Travers P; Lauster R; Hesse M; Dolling R; Mitchison NA 《International immunology》1997,9(11):1687-1699
Type II collagen (CII) is of immunological interest because of its
repetitive structure and properties as an autoantigen. The mouse gene has
recently been cloned, thus enabling T cell-defined epitopes to be
identified. Multiple novel epitopes on mouse CII are here detected in the
autoreactive T cell response. The major response is directed to an epitope
with residues 707-721 located on the CB10 fragment. Some 25 other epitopes
are also recognized, including the autologous homologue of the 256-270
epitope which dominates in the response to foreign collagen. The cells
reactive with mouse collagen peptides were of Th1 type, as judged by
release of IFN-gamma. No significant reactivity was detected to mouse CII
peptides during ongoing disease. Alignment of the mouse epitopes revealed a
sequence motif with characteristic side chains at residues P1, P4 and P7,
and to a lesser extent at P5, within a nonamer core sequence. Binding of
these epitopes was simulated in a computer model of the I-Aq molecule,
where peptides with anchor residues at P1, P4 and P7 were indeed found to
fit the binding groove best. The spacing of pockets and the fine structure
of the binding surface of the I-Aq molecule meshes with the repetitive
structure of the collagen (X-Y-Gly), thus providing a likely explanation
for the occurrence of multiple epitopes. Comparison with human DR binding
motifs showed that the I-Aq motif resembles most closely that of the DR4
subtypes which predispose for rheumatoid arthritis.
相似文献
2.
R B Landewé A M Miltenburg F C Breedveld M R Daha B A Dijkmans 《The Journal of rheumatology》1992,19(9):1353-1357
OBJECTIVE: To investigate synergistic interaction between cyclosporine (Cy) and chloroquine (Chl) in an in vitro system, with regard to interferon-gamma (IFN) production by OKT3 activated T cell clones. METHODS. CD4+ and CD8+ T cell clones, derived from synovial tissue of a patient with rheumatoid arthritis (RA) were activated with plastic coated OKT3 monoclonal antibody in the presence or absence of various concentrations of Cy, Chl and their combinations. After 24 h of incubation the supernatants were assayed for IFN by ELISA. RESULTS. Cy as well as Chl were able to completely inhibit in a concentration dependent fashion the IFN production by CD4+ and CD8+ T cell clones. Combinations of Cy and Chl, which in themselves give minor inhibition of IFN production, were able to inhibit in a synergistically enhanced fashion the production of IFN by these clones. The synergy was formally proven by the construction of isoboles. This synergy was most pronounced when drug concentrations were used which individually gave minor inhibition of IFN production. CONCLUSION. We conclude that the results of our in vitro experiments may give rise to further investigation of the promising combination of Cy and Chl in the treatment of RA. 相似文献
3.
4.
Endothelial cell lysis induced by lymphokine-activated human peripheral blood mononuclear cells 总被引:5,自引:0,他引:5
A M Miltenburg M E Meijer-Paape M R Daha L C Paul 《European journal of immunology》1987,17(9):1383-1386
In vitro exposure of human peripheral blood mononuclear cells (PBMC) to interleukin 2 results in the generation of lymphokine-activated killer (LAK) cells. Such LAK cells exhibit cytotoxicity against a spectrum of tumor target cell lines whereas they apparently do not affect normal tissues. In this report we show that PBMC that have been activated with T cell growth factor lyse trypsinized human umbilical cord venous endothelial cells as well as endothelial cell monolayers in a dose-dependent manner. Microscopic analysis showed that during the 4-h incubation period cell clumps containing detached endothelial cells and LAK cells were formed. When these clumps were evaluated with trypan blue the endothelial cells stained positive whereas LAK cells excluded the dye. No lysis occurred when fresh PBMC were added to target endothelial cells. The endothelial cell kill could not be blocked with an anti-LFA-1 antibody nor with intact OKT3 or F(ab')2 fragments of WT32. We conclude that lymphokine-activated PBMC exhibit cell-mediated endothelial cell detachment and lysis. 相似文献
5.
D. van Riessen M. R. Daha T. J. M. Smeets F. C. Breedveld 《Rheumatology international》1992,12(1):1-5
Summary It has been suggested that the reduced resistance of patients with rheumatoid arthritis (RA) to bacterial joint infections may be due in part to polymorphonuclear cell (PMN) function. To obtain further insight into the mechanis that contribute to the increased susceptiblity of RA patients to such infections we investigated the influence of different solid surfaces on the ingestion of various bacterial strains by PMN. Both in the presence and absence of serum, phagocytosis of bacteria by PMN was significantly lower on monolayers of synovial fibroblasts as compared to monolayers of endothelial cells and embryonic fibroblasts. It could be shown that the relative influence of the solid surfac on the results of the phagocytosis assay increased when decreasing concentrations of purified IgG were used. The results of this study sugpurified IgG were used. The results of this study suggested that the effect of synovial fibroblasts on PMB may lead to reduced clearance of bacteria from the joint. 相似文献
6.
Kupffer cell depletion in vivo results in clearance of large-sized IgA aggregates in rats by liver endothelial cells. 总被引:3,自引:1,他引:2 下载免费PDF全文
W M Bogers R K Stad D J Janssen F A Prins N van Rooijen L A van Es M R Daha 《Clinical and experimental immunology》1991,85(1):128-136
We investigated the clearance kinetics and tissue distribution of different sized IgA in normal and macrophage-depleted rats. Rats were injected iv with liposomes containing dichloromethylene diphosphonate (DMDP). DMDP treatment resulted in complete depletion of liver macrophages 24-48 h after administration. Normal and macrophage depleted rats were injected intravenously with monomeric, dimeric, polymeric or aggregated polymeric IgA (AIgA) and assessed for blood clearance and tissue distribution. In normal rats, clearance of IgA was size dependent, i.e. a faster clearance with increasing size. No differences in clearance kinetics were observed of the different sized IgA between normal and DMDP-treated rats. TCA non-precipitable radioactivity, a measure for degradation of IgA, was found in the circulation of normal and DMDP-treated rats after AIgA administration. The liver was the main organ responsible for the clearance of IgA in normal and DMDP-treated rats. Immunofluorescence studies on liver biopsies indicated that AIgA was associated with Kupffer cells in normal rats. Electron microscopical studies revealed that the AIgA was internalized and located in vesicles in Kupffer cells. In DMDP-treated rats the AIgA was associated with endothelial cells and electron microscopy studies showed that this AIgA was taken up by endothelial cells. These data show that rat liver endothelial cells are able to bind, internalize and degrade AIgA in situations where Kupffer cells are absent, and that these cells may play an important role in the handling of AIgA and IgA-immune complexes. 相似文献
7.
Characterization of anti-endothelial cell antibodies in systemic lupus erythematosus (SLE). 总被引:4,自引:2,他引:2 下载免费PDF全文
J M van der Zee C E Siegert T A de Vreede M R Daha F C Breedveld 《Clinical and experimental immunology》1991,84(2):238-244
IgG anti-endothelial antibodies (AEA), as measured by ELISA or immunoblotting technique could be detected in serum samples of 56 out of 64 patients with SLE (88%) and mainly occurred in monomeric form. AEA were not cell specific, because the binding reactivity was absorbed partially by both fibroblasts and peripheral blood mononuclear cells. No correlation was found between the presence of AEA and anti-nuclear antibodies. Immunoblotting revealed reactivity of AEA against endothelial antigens ranging in size from 15 to 200 kD. AEA titres were significantly higher in patients with joint or skin abnormalities, compared with patients without these abnormalities. A significant correlation was found between nephritis in SLE and the presence of AEA reactivity against endothelial membrane antigens of 38, 41 and 150 kD. These data show that the pattern of AEA reactivity in serum of SLE patients is heterogeneous, and suggest that AEA against a limited number of antigens may be involved in the pathogenesis of nephritis in SLE. 相似文献
8.
Seelen MA Trouw LA van der Hoorn JW Fallaux-van den Houten FC Huizinga TW Daha MR Roos A 《Clinical and experimental immunology》2003,134(2):335-343
In systemic lupus erythematosus (SLE), autoantibodies directed against complement components of the classical pathway, especially against C1q, are associated with severe disease and are of prognostic value for flares of lupus nephritis. Mannose-binding lectin (MBL), the recognition unit of the MBL pathway of complement activation, has structural similarities to C1q. Deficiencies of MBL have been shown to predispose to the development of SLE and to influence the course of the disease. We hypothesized that the presence of autoantibodies to MBL, analogous to autoantibodies to C1q in patients with SLE, may contribute to disease development. The occurrence of anti-MBL autoantibodies was assessed by enzyme-linked immunosorbent assay (ELISA) of 68 serum samples from 20 patients with SLE and in serum from 70 healthy controls. Levels of antibodies directed against MBL were significantly higher in patients with SLE compared to healthy subjects. No significant difference was found between patients with active disease compared to those with inactive disease. While the occurrence of anti-C1q autoantibodies was associated with renal involvement, no such relationship was found for anti-MBL autoantibodies. A significant correlation was found between anti-MBL and anti-C1q antibody levels. The level of anti-MBL antibodies was negatively correlated with MBL-complex activity of circulating MBL. Anti-MBL autoantibodies were of the immunoglobulin G (IgG) isotype and the binding site of IgG anti-MBL was located in the F(ab')2 portion. We conclude that anti-MBL are present in sera from SLE patients and influence the functional activity of MBL. 相似文献
9.
Analysis of large-cell lymphomas using monoclonal and heterologous antibodies. 总被引:3,自引:0,他引:3 下载免费PDF全文
P van der Valk G van den Besselaar-Dingjan M R Daha C J Meijer 《Journal of clinical pathology》1983,36(1):44-50
Fifteen cases of large-cell lymphoma, diagnosed as centroblastic (5), B-immunoblastic (5) or true histiocytic (5). lymphoma and one case of malignant histiocytosis were studied with monoclonal antibodies. Each diagnosis was based on morphological as well as marker studies. A panel of monoclonal and heterologous antibodies against T lymphocyte differentiation antigens (Leul, Leu2a, Leu3a, OKT4, OKT8, TA1), B lymphocyte subsets (BA1, BA2, HLA-DR, alpha C3b receptor antiserum, surface immunoglobulins), the common acute lymphoblastic leukaemia antigen (CALLA), monocytes/macrophages (OKM1, anti-human monocyte 1, TA1, Mac1, HLA-DR, anti-C3b receptor), myeloid cells (VIM-D5, elastase, OKM1) and the cells of the Langerhans cell/interdigitating reticulum cell series (OKT6, NA1/34). The results show a specific staining pattern for true histiocytic lymphoma (histiocytic sarcoma). Centroblastic and B-immunoblastic lymphomas showed gradual differences with mostly strong staining for HLA-DR and weak with anti C3b receptor for B-immunoblastic lymphomas in contrast to centroblastic lymphomas. Staining with BA1 and BA2 indicated immunological heterogeneity in these lymphomas. The number of admixed cells was usually low with few B cells and a shift in the ratio helper/inducer to suppressor/cytotoxic T cells in favour of the suppressor/cytotoxic subset. 相似文献
10.
Relative importance of C4 binding protein in the modulation of the classical pathway C3 convertase in patients with systemic lupus erythematosus 下载免费PDF全文
M R Daha H M Hazevoet J Hermans L A van Es A Cats 《Clinical and experimental immunology》1983,54(1):248-252
Serum concentrations of C1q, C4, C4 binding protein (C4bp), C3 and C2 haemolytic activity have been measured in 110 samples from 20 patients with systemic lupus erythematosus (SLE). Significant reductions in comparison to normal levels were found in the mean serum concentrations of C4, C3 and C4bp as well as C2 haemolytic activities. For patients serum concentrations of C4 correlated with C2 haemolytic activities (r = 0.91) and C4bp (r = 0.79); the C2 haemolytic levels correlated with the concentration of C4b (r = 0.72). It is concluded that serum concentrations of the complement components C4 and C2, which are the constituents of the classical pathway C3 convertase, are regulated by C4bp in vivo. Further metabolic studies are required to determine the causes of decreased serum concentrations of C4bp in patients with SLE. 相似文献