摘要:

The interaction between immune aggregates and complement (C) was investigated Solid‐phase immune aggregates were prepared by coating microwells with heat‐aggregated bovine serum albumin (BSA) followed by rabbit anti‐BSA antibody. The immune aggregates were reacted with human serum or citrated plasma al 370C. The binding of C3 components was investigated with biotinylated F(ab′)2antibodies In C3c and C3d and avidin‐coupled alkaline phosphatase. The form of the incorporated C3. whether C3b‐iC3b or C3dg. can be deduced from the response with these two antibodies. The maximal binding of C3b‐iC3h to the immune aggregates was observed within 5 min of incubation with serum or citrated plasma The conversion to C3dg was evident by a decrease in bound anti‐C3c concomitant with increasing anti C3d reactivity within about 10min of incubation. When the classical C pathway activation was inhibited, the binding of C3b‐iC3b was delayed by 20–30 min. whereas stopping of the alternative pathway did not influence the initial kinetics of the reaction. The addition of human red blood cells had no measurable influence on the degradation of bound C3b‐iC3b.125I‐lebelled anti‐BSA antibody bound to the solid‐phase BSA was not released during the C3 incorporation. The incorporation of C3b into the immune aggregates was mediated equally well by serum and by citrated plasma. The incorporation of C3b‐iC3b into immune complexes (IC) is thought to be responsible for the C‐mediated solubilization (CMS) of IC. Citrated plasma, however, exerted no CMS capacity when measured by a radiometric assay, The CMS capacity of serum was inhibited by citrate, but could then be restored by adding Ca2+and Mg2+, whereas no CMS could be demonstrated with citrated plasma to which

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1986.tb03071.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Human thymocytes were separated into 10 fractions by continuous Percoll density gradient centrifugation. Almost all the cells able to proliferate in response to phytohaemagglutinin (PHA) and about 80% of the thymocytes carrying the mature T3 marker were contained within the first two lightest fractions (Fr1 and Fr2), However, cells in Fr1 and in Fr2 were clearly different in terms of their interleukin requirement for mitogenesis. i.e., in the presence of interleukin‐1 (IL‐1). Fr1 thymocytes showed proliferative responses to PHA that were three to five times greater than those of the Fr2 cells, whereas in the presence of exogenous IL‐2 both Fr1 and Fr2 cells bad mitogenic responses of a similar magnitude. These differences could not be explained by accessory cell contamination or by different kinetics of the proliferative responses. Furthermore, in the presence of exogenous IL‐1. Fr1 thymocytes showed a greater capacity for producing IL‐2, In contrast, there was no difference in the expression of functional IL‐2 receptors between the two fractions. It can be concluded that the mature thymocyte subpopulation contains at least two functionally distinct subsets, which differ in density, and that during intrathymic maturation the capacities to produce and to respond to IL‐2 do not develop simultaneously. Although both the number and the binding characteristics of glucocorticoid (GC) receptor sites did not differ significantly between Fr1 and Fr2 thymocytes. dexamethasone was more effective in inhibiting the PHA‐induced mitogenesis of Fr2 than of Fr1 cells. Thus, the GC sensitivity of T‐cell mitogenesis is not directly correlated with receptor‐related variables. In contrast with observations made on peripheral T cells, the inhibitory activity of GC on thymocyte mitogenesis was only partially reversed by the addition of exogenous IL‐2, Thus, the inhibitory action of GC on thymocyte mitogenesis cannot be explained only by the steroid‐induced inhibition of IL‐1‐IL‐2 production; it must also be due to a GC‐inhibitory effect on the IL

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1986.tb03072.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Three strains of mice hearing the autosomal recessivelprgene (MRL. C57BL/6 and C3H)that had spontaneously developed a lupus‐like disease were studied sequentially for functional natural killer (NK) and natural cytotoxic (NC) cell activity. Natural killing was impaired in spleen and bone marrow cells from all thelprstrains, as well as from the congenic strain MRL‐ +/+. which develops a late onset lupus‐like disease. The NK cell activity was found to be depleted as early as 2 months of age in alllprstrains, and decreased further with age. NK activity was augmentable by Poly I: C and interleukin 2 (IL‐2). suggesting that the residual cells can respond to NK modulators. In contrast with NK cell activity. NC activity was not decreased inlprmice but could be augmented by IL‐3‐rich supernatants. The spontaneous decrease in NK cell activity was associated with an increased autologous plaque‐forming cell (APFC) response to bromelin‐treated mouse red blood cells, which is produced primarily by B cells possessing the Ly‐1 phenotype (Lyt‐1+B). When NK cell activity was increased by exogenous administration of Poly I:C, the APFC response diminished. Treatment of spleen cells with anti‐asialo GM1prior to Poly I: C treatment resulted in a decreased NK response but increased both APFC and Lyt‐1+B cells. The possible regulation of autoreactivity b

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1986.tb03073.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

BALB/c mice were immunized with human islets of Langerhans and spleen cells from two mice. found to develop cell‐surface antibodies against insulin‐producing rat islet tumour RIN‐5F cells, were fused with mouse myeloma cells. Antibody‐producing hybrids were cloned on the basis of their production of surface antibodies reactive with paraformaldehyde‐fixed RIN‐5F cells by indirect immunofluorescence analysis in the fluorescence‐activated cell sorter. Among 236 primary clones, eight stable cell lines producing islet‐cell‐surface antibodies were eventually cloned. Antibody 2G3 (IgM) reacted with viable normal rat islet cells and high insulin‐producing rat islet tumour RIN5‐A2 cells, while 3G3(IgM) only reacted with RIN5‐A2 cells. AntibodyβB1 (IgG1) reacted with all islet cells tested and detected anM121k component in immunoblotting experiments with RIN‐5AH cell plasma membrane proteins electrophoretically transferred to nitrocellulose filters. Antibody 7F6 (IgM) reacted with all islet and non‐islet cells tested and delected bands ofM166k and 27k by immunoblotting. Antibodies γB3,γB6, γC2, and 6BI (all IgM) showed varying degrees of binding to different islet cells, but reacted only weakly with non‐islet human cells. It is concluded that monoclonal antibodies against pancreatic islet cells may define specific endocrin

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1986.tb03074.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Cyclosporin A (CyA) is the immunosuppressive treatment of choice in preventing allograft rejection and graf‐versus‐host disease. However, clinical trials indicate that there may exist inter‐individual variations in sensitivity to the drug. We have approached this issue by studying CyA‐mediated inhibition of in vitro alloreactions. as measured by mixed lymphocyte reactions (MLR) and cell‐mediated lympholysis (CML), using mouse and human normal spleen cells. The differences between individuals in the CyA concentration required 50% inhibition of the human alloreactions were twentyfold for the MLR and fortyfold for the CML. Moreover, the CML appeared to be inhibited, at lower doses of the drug. No correlation was found between inhibitory doses and variables such as the magnitude of the response, age, or human leukocyte antigen phenotype. When the same experiments were performed with mouse spleen cells, no differences were observed among eight inbred strains. The lack of demonstrable individual sensitivity of mice in relation to humans is

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1986.tb03075.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

The present study was undertaken to determine directly whether immunoregulatory T cells have a defective suppressor function in patients with systemic lupus erythematosus (SLE), and whether anti‐T‐cell antibodies are essential for immunoregulatory T‐cell defects. Peripheral blood T cells and T‐cell subsets were determined in 52 SLE patients. The ratio of T4 to T8 cells was distributed over a wider range in patients with SLE than in the controls. Patients with SLE were divided into three groups (low, normal and high) by the T4/T8 ratio. Lymphocytes from 12 SLE patients (7 with low and 5 with high T4/T8 ratios) were studied extensively. Their disease was inactive or in remission, Anti‐T‐cell antibodies were not detected, and yet the patients had immunological abnormalities characterized by the presence of antinuclear antibodies and hypergammaglobulinaemia. The SLE patients with high T4/T8 ratios had a decreased number of'T8 cells, and defective suppressor‐effector cells. In contrast, patients with low T4/T8 ratios had decreased T4 cells and/or increased T8 cells, and defective suppressor‐inducer cells. Two patients with low T4/T8 ratios had both suppressor‐effector and suppressor‐inducer cell defects. These results indicate that immunuregulaiory circuits in SLE patients are heterogeneous and that immunoregulatory defects exist even when the disease is inactive or in remission. Anti‐T‐cell antibodies were not essential for such immunoregulatory defects. Thus, immunoregulatory T‐cell defects and the development of SLE may be independent conditions du

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1986.tb03076.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

Using magnetic monosized polymer particles (M 450) coated with a monoclonal mouse IgM anti‐CD8 (ITI 5C2) antibody, we were able to selectively remove and isolate functionally active CD8+T cells from human peripheral blood mononuclear cells. Isolated CD8+cells did not respond by proliferation lo soluble antigens, but proliferated in response to phytohaemag‐glutinin. However, in the presence of CD4+T cells. CD8+cells were able to mount a substantial proliferation when stimulated with soluble antigens. Depletion of CD8+cells decreased rather than increased the T‐cell responses to the antigens glyc‐gli, Coxsackie B4, and mumps in healthy individuals. We therefore found no indication of involvement of functionally‐active CD8+‐ suppressor cells in vitro, The T‐cell responsiveness to these antigens has previously been shown to be influenced by HLA‐DR‐associated restriction elements, but the tendency for decreased responsiveness to these antigens by CD8 depletion seemed independent of the DR type of the cell donors. As in healthy subjects. CD8 depletion resulted in a decreased responsiveness to the gluten antigen glyc‐gli in untreated and treated coeliac disease patients and to Coxsackic B4 and mumps antigens

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1986.tb03077.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

The role of CD8 (T8, Leu 2)‐positive T lymphocytes in the proliferative T‐lymphocyte response to mumps and Coxsackie B4 viral antigens in vitro was investigated. The frequency among enriched T‐lymphocyte blasts of antigen‐reactive T lymphocytes (ARTL) restricted by different DR‐associated elements was investigated, using antigenic restimulation with allogeneic antigen‐presenting cells in a limiting dilution assay. A decreased frequency of DR3‐restricted and an increased frequency of DR4‐restricted mumps and Coxsackie B4 ARTL were seen in the limiting dilution assay, whether or not HLA class I determinants were shared in the antigenic restimulation. Removal of CD8‐positive cells did not increase the primary in vitro responsiveness to mumps and Coxsackie B4 viral antigens, and did not change the DR‐associated differences in the frequency of ARTL seen in the limi

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1986.tb03078.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

The frequencies of murine B‐cell precursors developing into clones secreting antibodies which hind to autologous (mouse) or heterologous (rabbit or human) forms of the same protein antigen (myosin and albumin) were determined in an attempt to directly lest the hypothesis of higher decay rates of B lymphocytes exposed to self‐antigens. The results exclude, on a quantitative basis, any form of inactivation or deletion of such ce

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1986.tb03079.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY

摘要:

The further characterization of internal image anti‐idiotypic antibodies (anti‐Id) that represent a potential alternative vaccine candidate for type B viral hepatitis is described. The anti‐Id preparation contains an internal image component or related epitope that mimics hepatitis B surface antigen (HBsAg) and binds to murine hybridoma cells that secrete antibodies to HBsAg (anti‐HBs). This binding to anti‐HBs‐secreting hybridomas was partially inhibited by intact HBsAg particles and was associated with the expression of an interspecies idiotype. Immunoprecipitation studies demonstrated that the anti‐Id bound to immunoglobulin molecules expressed on the surface of the hybridoma cells. These data suggest that internal image anti‐Id, which induces an in vivo antibody response by antigenic mimicry in the absence of HBsAg, binds to anti‐HBs molecules on the surface of cells actively secreting anti‐HBs. The possible mechanism for internal image anti‐Id‐based antibody vaccines that mimic the overall conformation of antigens associated with infecti

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1986.tb03080.x

出版商:Blackwell Publishing Ltd    

年代:1986

数据来源: WILEY