ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02736.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02737.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Sarcoidosis is a granulomatous disorder of unknown aetiology. Alveolar macrophages (AM) in sarcoidosis release a variety of mediators important to the pathogenesis of the disease. Complement is essential for the inflammatory response and we investigated whether there were any major defects in the potential for sacroidosis AM to synthesize complement in vitro. AM from 11 patients with active sarcoidosis and three healthy controls were cultured under serumfree conditions, There was a significant binding of polyclonal (anti‐C5, ‐C6, ‐C7, ‐C8) and monoclonal anti‐complement antibodies (anti‐C3c and anti‐C9 neoepitope (aE11)) to agarose beads incubated with unstimulated AM for 24, 48, or 72 h, A significant and inhibitable production of soluble C3c, C5, C9, and S‐protein was found in the harvested medium as detected by enzyme immunoassays. Activated C3 and C9 were also detected on neoepitope expression. Presence of co‐cultured agarose beads reduced the amount of soluble S‐protein due to deposition on the agarose. We argue that the C9 neoepitope is an integral part of the terminal complement complex (TCC), both in the fluid and solid phase when bound to the agarose. In the fluid phase. SC5b‐9 was generated, whereas the agarose‐bound S‐protein is assumed not to be associated with TCC on the beads. The results demonstrate for the first time that AM from sarcoidosis patients synthesize the functional alternative a

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02738.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

In this report we compare the effect of stimulation of peripheral mononuclear cells (PBMC) by using two monoclonal antibodies (MoAb) directed against the CD2 receptor on T cells or by using autologous erythrocytes (E) which express on their surface lymphocyte function‐associated antigen 3 (LFA3), a natural ligand for CD2. The addition of autologous erythrocytes to pokeweed mitogen (PWM)‐stimulated PBMC results in ihe enhancement of polyclonal immunoglobulin synthesis and of antigen‐specific B‐cell responses. Because B cells lack the CD2 molecule, it can be concluded that their enhanced activity is a consequence of the delivery of activating signals by activated T lymphocytes. When PBMC cultures were stimulated with a pair of anti‐CD2 MoAb (Leu5b and VIT13) we were able to induce polyclonal immunoglobulin synthesis, particularly IgM, in cultures supplemented wilh interleukin 2 (IL‐2). Specific responses to telanus toxoid (TT) and keyhole limpet haemocyanin (KLH) were also enhanced by the addition of autologous E to PWM‐stimulated PBMC. Significant anti‐TT responses were observed in cultures stimulated with E+TT+IL‐2. In contrast, stimulation of PBMC wilh VIT13+Leu5b+IL‐2+antigen was not effective in inducing anli‐TT antibody and only weakly effective in inducing anti‐KLH antibodies. Replacing Leu5b by anti‐CD3 had no effect on the induction of specific antibody responses; in contrast, replacement of Leu5b by E enhanced anti‐TT antibody production while the effect on polyclonal production of IgM was minimal. Therefore, it appears that the signal delivered by the association of CD2 with LFA3 is a better potentiating signal for specific B‐cell responses than the signal delivered by pairs of MoAb to different epitopes of C

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02739.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

antibodies from theresulting lines and clones were examined for their binding to a variety of auto‐antigens and micro‐organisms by ELISA and fluorescence assays. Auto‐antigens tested included Fc of IgG, ssDNA and dsDNA, cardiolipin, histones 1‐4, collagens type I and II. thyroglobulin, cytoskeletal components, and a tissue section screen. Of 71 cell lines tested, all but 19 showed some autoreactivity. All 32 fetal liver lines reacted to some seif‐antigens. In cord blood clones, 16 out of 26 bound to auto‐antigens. Many of the clones reacted with more than one auto‐antigen and were ‘polyrcactive’. Some of the cord blood clones bound to extracts of micro‐organisms, showing specificity for both endogenous and exogenous antigens. The high frequency of CD5+ B cells in the cord blood (>50%) and fetal liver (>70%) argues for many of these clones being derived from this subset. Therefore, our data support the concept that many ‘early’ B cells produce polyreactive IgM which can bind to a variety of different auto‐antigens and microorganisms. These IgM antibodies are similar to those described by other

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02740.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

We have previously demonstrated the pathogenicity of the common anti‐DNA idiotype designated 16/6 Id. Immunization of naive mice with the 16/6 Id induced SLE‐like disease characterized by serological (e.g. anti‐dsDNA and anti‐Sm auto‐antibodies), clinical (increased ESR, leucopenia and proteinuria), and pathological (16/6 Id deposition in kidneys) parameters. To elucidate further the role of the 16/6 Id in SLE induction the following studies were carried out: BALB/c mice were immunized with SA‐1, a human anti‐DNA monoclonal antibody carrying the 16/6 Id; TB‐68, a mouse monoclonal anti‐tuberculosis (TB) glycolipid, which binds dsDNA and carries the 16/6 Id; TB‐72, a mouse monoclonal anti‐TB glycolipid that binds DNA and does not harbour the 16/6 Id; and 4B4, a human anti‐Sm antibody that carries the 16/6 Id. SLE was induced in BALB/c mice only when immunized with SA‐l, TB‐68, and 4B4, namely antibodies with diverse binding capacities albeit having the 16/6 Id. Our studies further support previous evidence on the pathogenic role attributed to the 16/6 Id in SLE, and suggest that SLE is most probably

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02741.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Rats were immunized with ovalbumin, either subculaneously or by aerosol inhalation. The lymphocyte distribution in lymph nodes, peripheral blood, and spleen was investigated by flow cytometry after labelling with T pan (0X19 and W3/13), T helper lymphocytes (W3/25), T cytotoxic/suppressor lymphocytes (OX8), k light chain (MAR 18‐5), or MHC class II (0X6) monoclonal antibodies. The influence of the neurotoxic agent capsaicin on the lymphocyte distribution was also analysed. Subcutaneous immunization resulted in an increased number of OX8+ cells in mesenteric lymph nodes, spleen, and peripheral blood but not in the draining lymph nodes, axillary, brachial, and mediastinal lymph nodes. The number of positive cells for the other cell markers used were not affected by immunization. The neuromodulatory effect of capsaicin had no effect on the lymphocyte distribution. The results showed that the type of immunization used, low amounts of antigen without adjuvant given during a prolonged period, selectively induced OX8+ cells. The patterns were unaffected by neuromodulation using capsaici

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02742.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Plasma and serum samples from a patient with homozygous C2 deficiency and severe systemic lupus erythematosus who responded with full clinical remission after plasma infusions were examined for immune complexes (IC), C3 activation products, and the terminal complement complex (TCC). Plasma contained large amounts of C4‐containing IC but no C3‐containing IC or complement activation products. Classical pathway activation in vitro did not lead to C3 activation or TCC formation as seen in normal serum, but a very efficient binding of C1q and C4 was found. No disturbances in alternative pathway activation were observed. The results indicate an impaired formation of C3‐containing IC and an inefficient clearance of C4‐containing IC, supporting the idea of a causal relationship between the dysfunctional classical pathway, pathophysiology, and clinical manifestations in this

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02743.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

In Brown‐Norway (BN) rats mercuric chloride induces an autoimmune disease characterized by an increase in serum IgE concentration, and by the production of anti‐glomerular basement membrane antibodies responsible for a glomerulonephritis with a heavy proteinuria. (i) This disease results from a B‐cell polyclonal activation probably due to frequent anti‐class II T cells. (ii) The self limitation observed in this model is associated with both a decrease in the frequency of anti‐class II T cells and the emergence of CD8+ T cells able to suppress these autoreactive T cells. (iii) In Lewis (LEW) rats which do not develop autoimmunity, HgC12 provokes the appearance of non‐antigen‐specific CD8+ T cells responsible for a depression of T‐cell functions. The aim of this work was to test the effect of treatment with an anti‐CD8 monoclonal antibody (MoAb) in both BN and LEW rates, Anti‐CD8 MoAb‐treated rats were effectively depleted in CD8+ T cells. However, neither the induction nor regulation phases of mercury‐induced autoimmunity were modified in BN rats. Mercury‐induced immunosuppression in LEW rats was abrogated; however, depletion in CD8+ T cells did not allow the disease to occur in that strain. Finally, CD8 depletion induced in normal BN rats rats the appearance of rare anti‐class II T cells showing that these cells are normally present in that strain but negatively contr

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02744.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY

摘要:

Activation of resting T cells to proliferate is usually accompanied by their expression of interleukin 2 receptors (IL‐2R) and secretion of (IL‐2). We studied the mechanisms by which human blood‐derived dendritic cells (DC) and monocytes induce IL‐2R and stimulate IL‐2 secretion in autologous and allogeneic mixed luecocyte reaction (auto‐ and allow‐MLR, respectively). We found that only DC were fully effective as stimulator cells in MLR. DC stimulated both autologous and allogeneic T cells to express high‐affinity IL‐2R, secrete IL‐2, and vigorously proliferate in MLR. The stimulatory properties of monocytes were more complicated: although they stimulated the proliferation in allogeneic MLR, the proliferation rates, duration, and amount of IL‐2 secretion were different than in DC‐induced MLR. Autologous T cells did not proliferate in response to monocytes, but were induced to express the low‐affinity IL‐2R. If the cultures were supplemented with exogenous recombinant IL‐2, the proliferative responses to DC and monocytes in auto‐ and allo MLR were of the same magnitude, indicating that the responsiveness to IL‐2 was stimulated by both the stimulator cells. The stimulator cell number was important, since large numbers of monocytes, but not of DC, were suppressive to the proliferative responses. Thus, we concluded that the higher capacity of DC, as compared to monocytes, to stimulate T‐cell proliferation is based primarily on the more effi

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1990.tb02745.x

出版商:Blackwell Publishing Ltd    

年代:1990

数据来源: WILEY