摘要:

Our objective was to investigate the patterns of proliferation and differentiation of infiltrating cells in inflammatory myopathies. Immunohistochemical staining was performed on muscle biopsy specimens from 18 patients with inclusion body myositis, polymyositis and dermatomyositis using monoclonal and polyclonal antibodies.An abundance of cells were TNF‐α+(4–8%), ICAM‐1+(7–65%). IFN‐γ+(3–6%), and Ki‐67+(4–8%). It was shown that 70% of the Ki‐67+cells were Ki‐67+CD3+cells. Very few mononuclear cells were IL‐2R+. MHC‐I expression was found on nearly all muscle fibres in all cases, while MHC‐II expression was found on occasional muscle fibres in 1/3 of cases. Analysis of repeated biopsies from four IBM patients after prednisolone treatment showed no change in the proportions of TNF‐α, ICAM‐1, IFN‐γ or Ki‐67 positive cells. In inflammatory myopathies there is an intense proliferation and differentiation of inflammatory cellsin situ, indicating a local st

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03587.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

In the present study we evaluated the effect of passive transfer of a mouse monoclonal (CAM) or a human polyclonal anti‐cardiolipin IgG on pregnancy outcome in BALB/c mice. The mice were immunized through the tail vein immediately after mating with 10 μg of monoclonal or polyclonal anti‐cardiolipin antibodies. Two other groups of mice were given a mouse irrelevant monoclonal antibody or normal human polyclonal IgG respectively, at the same dose. In mice immunized with monoclonal or polyclonal anti‐cardiolipin antibody we observed a significant increase in the number of fetal resorptions and a significant reduction of the mean weights of the embryos and the placentas. In mice immunized with CAM we also found a significant decrease in the number of healthy pups, while mice infused with human aCL antibody expressed a significant reduction in the fecundity rate. The histological examination showed widespread thrombosis and necrosis in the placentas derived from the mice immunized with the anti‐cardiolipin antibodies. The model supports a possible direct pathogenetic effect of anti‐phospholipid antibodies in recurrent fetal loss and points out that thrombotic events at placental level can be instrumental in the pathogenesis of the obstetric com

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03588.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The secreted protein MPB51 is one of the major proteins in the culture filtrate ofMycobacterium bovisBCG (BCG) and is a protein immunologically cross‐reacting with the fibronectin binding 85 complex secreted by this bacterium. The gene encoding MPB51 (mpb51) was cloned, sequenced, and expressed inEscherichia coll.Thempb51gene was mapped downstream of the gene for 85A component with 179 bp spaces. Thempb51gene encoded 299 amino acids, including 33 amino acids for the signal peptide, followed by 266 amino acids for the mature protein with a molecular mass of 27807.37 Da. This is the first complete sequence of MPB51. MPB51 showed 37–43% homology to the components of 85 complex. Two‐dimensional electrophoresis of culture fluids of BCG and Western blotting indicated the existence of the other novel protein(s) which strongly cross‐reacted with the α antigen (85B) a

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03589.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The antigenicity of 36Humicola lanuginosalipase (HL) variants, generated by site directed mutagenesis, was compared with that of the unchanged enzyme. Polyclonal antibodies raised against variant lipases were investigated and compared with the antibodies raised against the wild type lipase in an ELISA competition assay. The results showed that exchange of charged amino acids with polar residues in surface epitopes of HL, results in a tighter binding of the antibody to the epitope. Four amino acids (Trp at position 89, Asp at positions 96 and 254 and Phe at position 211) were found to be essential for antibody binding in each their epitope of the wild type enzyme.

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03590.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

We have investigated the effect on complement activation of human irnmunoglohulins (Ig) using several therapeutic Ig preparations including two for intravenous use (IVIG), and various purified myeloma proteins. Ig inhibited lysis in a dose‐dependent manner in the classical pathway assay whereas no alternative pathway inhibition was observed. The Fc part of the molecule was responsible for all the inhibitory effect. Purified IgG3 myeloma proteins were potent inhibitors whereas IgGl inhibited to a lesser extent and lgG2 and IgG4 did not inhibit at all. Inhibition was obtained both when Ig was added to the solution and when it was coated onto a solid matrix. Analysis of the soluble and solid phase Ig after incubation revealed binding of Clq and activated C4 and C3 to the isotypes which inhibited lysis. Using selectively depleted sera and reconstitution with their respective purified components, efficient inhibition of lysis was seen when Ig was added prior to serum (C1), some inhibition was seen at the C4 level, whereas no effect was seen when Ig was added at the C9 level. We conclude that the complementmodulatory effect of Fgin vitrois isotype specific and dependent mainly on competitive C1 binding by the Ig molecule in the absence of antige

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03591.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Various mutations including gal E in the S. typhi vaccine strain Ty21a are thought to prevent proliferation of these micro‐organisms in the host, and elimination of Ty21a would occur independent of the immune system of the host. To investigate this issue, we determined whether Ty21a can proliferate in immunosuppressed mice, and assessed the role of phagocytes in the eradication of Ty21a from tissues. Mice were rendered lymphocytopenic and monocytopenic by hydrocortisone s.c., or were made leucocytopenic by whole body irradiation. Bacteria were injected into a tail vene to evaluate eradication from the blood, liver and spleen, and into thigh muscle, i. e. a tissue that lacks resident macrophages. Ty21a were grown overnight in glucose [glu], or galactose and glucose [gal. glu]; only the Ty21a [gal. glu] expressed somatic O‐antigens. After i. v. injection of 104to 106micro‐organisms, Ty21a were rapidly eliminated from the liver and spleen of normal and immunosuppressed mice, i. e. within 1 day a 95% reduction of bacterial counts was observed. After i. m. injection of 104to 106bacteria, the number of viable Ty21a decreased in normal and hydrocortisone‐treated mice, but in irradiated mice the microorganisms proliferated and caused generalized infection. In all cases, Ty21a [glu] was eliminated more rapidly than Ty21a [gal. glu], confirming reports that killing of bacteria that lack O‐antigens is more rapid than that of smooth bacteria of the same species. These results indicate that elimination of the vaccin strain against typhoid fever, Ty21a, from host tissues is not due to an intrinsic property of the micro‐organisms that prevents proliferation but instead depends on the action of resident macrophages and exudate monocytes and g

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03592.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

IL‐6 is a potent regulator of T‐cell activation, proliferation and differentiation. Since IL‐10 inhibits cytokine production by T cells, the effect of IL‐10 on IL‐6 production by T cells was investigated. IL‐6 production by purified monocytes or T cells was detected from cell‐free culture supernatants by ELISA after stimulation of the cells with LPS or an anti‐CD3 monoclonal antibody for 3 days. Although the main source of IL‐6 are LPS activated monocytes (29.6 × lOng/ml), T cells secreted sufficiently high levels of IL‐6 (790 × 200pg/ml) to stimulate the high affinity IL‐6 receptor. IL‐10 decreased anti‐CD3 induced IL‐6 mRNA expression by up to 80%. In addition, IL‐10 significantly inhibited IL‐6 release from T‐cells. Highly purified, anti‐CD3 activated T‐cells secreted 600 × 150pg/ml IL‐6 compared to 21 × 2pg/ml IL‐6 following addition of IL‐10 (10ng/ml; P<0.001). FACS analysis revealed a monocyte contamination of the T‐cell preparations of less than 0.5%. In addition, no IL‐1 production was detectable. Thus, in our experiments the effect of TL‐10 on IL‐6 production was independent of the presence of monocytes. Finally, inhibition of IL‐6 production was not reversed by IL‐2 (100U/ml). In conclusion, IL‐10 suppressed the synthesis of IL‐6 by T‐cells via a monocyte‐and IL‐2‐independeni mechanism. These results may help to understand

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03593.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The effect of long termin vivoadministration of IL‐4 on the induction of antigen‐specific B cells, the splenic microenvironment and the yield of antigen‐specific antibody producing hybridomas was studied. Immunization with DNP‐KLH, followed by 12 weeks continuous IL‐4 treatment resulted in increased numbers of total splenic (non‐DNP) IgM and IgG AFC (antibody forming cells) on day 5 after booster, whereas the DNP‐specific IgG and IgG1 AFC were reduced compared to age‐matched control animals not treated with IL‐4. In addition, an almost 300‐fold increase in non‐DNP IgE was found while the IgE anti‐DNP response was minimal.When the splenic cells were used in a fusion protocol, a relative decrease in yield of antigen‐specific hybridomas was found in the long term IL‐4 treated mice. Immunohistological staining of spleen sections from mice treated with IL‐4 up until the time of booster revealed reduced B‐cell follicle area and germinal centre numbers. These results show that extensive IL‐4 treatment reduced antigen‐specific B‐cell formation and suggests a reduction in the number of B cells entering th

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03594.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

The ganglioside GD3 has a variety of biological functions. These include stimulatory effects is on proliferation, natural killer activity and cytokine production by freshly isolated peripheral T cells. In this study we have characterized anti‐GD3 antibody (MoAb Z21) mediated effects on T cell clones. Our data indicate that α/β TCR CD4+and CD8+as well as γ/δ TCR positive T cells can be stimulated resulting in proliferation and cytokine production. This effect could be blocked by cyclosporin A and did not involve the LFA‐3 or CD4 molecule. Apart from IFN‐γ and IL‐2 production by T helper I and T helper 0 cells we have observed production of IL‐4 and IL‐10 by T helper 2 cells indicating that the GD3 molecule is not a marker for a certain functional T cell subset. In contrast to anti‐CD3 mediated activation, the responsiveness of T cells to stimulation via GD3 was dependent on the cell surface expression of the molecule and could be enhanced by costimulation via CD2, CD3, CD26 or CD28. In addition, anti‐GD3 antibodies delivered a potent costimulatory signal for antigen‐induced proliferation of CD4+T lymphocytes. In summary, our experiments illuminate the mechanisms of anti‐GD3 antibody i

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03595.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

We document here the identification of germinal centres with dark and light zones, a follicular dendritic cell network and clonal expansion in the synovium of rheumatoid arthritis patients. Synovial tissue from 24 patients suffering from rheumatoid arthritis or the polyarticular form of juvenile rheumatoid arthritis were screened for the presence of lymphoid follicles. The synovial tissues of 14 patients contained follicles and four of these had germinal centres and a follicular dendritic cell network. There was a statistically significant association between follicles in the synovium and the presence of rheumatoid factor autoantibodies in the patients' serum indicating a link between local germinal centre formation and the presence of pathological rheumatoid factors. Nucleotide sequencing of monoclonal rheumatoid factors from one of the patients' synovial tissue which contained germinal centres clearly supports the possibility that these rheumatoid factors have gone through a germinal centre reaction. While rheumatoid factors from healthy immunized donors are regulated through a tolerization mechanism which selects against replacement mutations and does not allow affinity maturation, synovial rheumatoid factors seem to lack this tolerization mechanism. The formation of germinal centres where B cells affinity mature and expand at the central site of disease in rheumatoid arthritis may explain why rheumatoid factors in rheumatoid arthritis develop into auto‐aggressive antibodie

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1995.tb03596.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY