ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb03124.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

SummaryThe study of the immunobiology of FVIII inhibitors may lead to new therapies for this potentially severe complication of haemophilia A and to new principles for the use of therapeutic proteins. In order to characterize the idiotype‐anti‐idiotype networks regulating FVIII inhibitors, we developed rabbit antiidiotypic sera to 7 murine inhibitors and found at least 12 independent FVIII loci to which inhibitors could be raised. Rabbit antisera to the FVIII peptide. Ser1687‐Thr1695characterized one functional site to which about 46% of patients' inhibitor sera reacted. The multiplicity of inhibitor‐recognized epitopes in FVIII makes it impractical, at the present time, to develop clinically useful specific anti‐idiotypic therapies for FVIII inhibitors. Alternatively, one might induce genomic mutations in recombinant FVIII molecules to decrease immunogenicity of epitopes recognized by T helper cells. Methods to design such altered therapeutic proteins are presented, based on changing the longitudinal hydrophobic strip of‐helix which is in or near many T‐cell‐pre

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb03125.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Four immunization routes were investigated to induce an immune response against three structurally different types of pneumoccoccal polysaccharide (PPS) in the rat. In particular, the contribution of the IgA isotype in these immune responses was studied. Six days after administration of PPS type 3, 4 or 14. the localization of specific antibody‐containing cells (ACC) in different lymphoid tissues and the antibody titres in serum were studied.All four routes induced anti‐PPS ACC in the spleen. After intraduodenal, intravenous and especially intraperitoneal administration of PPS, many IgA‐specific anti‐PPS ACC were also found in parathymic and mesenteric lymph nodes and in the lamina propria of intestinal tissue. Several anti‐PPS ACC were found in Peyer's patches, located peripheral of the B‐cell areas. The intratracheal immunization elicited only a local immune response, in bronchus‐associated lymphoid tissues and paratracheal lymph nodes. The localization of these anti‐PPS ACC was influenced by the route of immunization.After all four investigated routes, specific antibodies were found in serum against PPS. However, some remarkable differences between PPS‐3, 4 and 14 were found in the magnitude of the immune response and the distribution of the isotypes. Both route of immunization and structure of the PPS have a profound influence on the immune

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb03126.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Previously we showed that pretreatment of LGL/NK or HUVE cells withSalmonellabacteria augments the adhesion of LGL/NK cells to endothelium. Here we analyse the roles of HUVEC adhesion molecules VCAM‐l, ICAM‐I and E‐selectin, and the counter‐receptors VLA‐4, LFA‐1 and SLe3in the increase of LGL/NK adhesion to HUVEC, stimulated withSalmonella MinnesotamR595 bacteria. LPS or TNF‐α.Onsalmonella‐stimulated HUVEC, VCAM‐l and ICAM‐1 were the major binding structures involved, and their effect was additive in monoclonal antibody inhibition experiments. We could demonstrate the induction of both structures on cultured HUVEC after 24 h ofSalmonellastimulation in flow cytometric analysis. Forsalmonella‐stimulaled LGL/NK, the principal binding structure was LFA‐1, Stimulation of LGL/NK cells did not alter the expression of the adhesion structures (subunits CD11a/CD18, CD49d/CD29). as determined by flow cytometric analysis, and thus the increased adherence is presumably produced by an increased avidity of the receptors on LGL/NK cells.Pretreatment of endothelium or lymphocytes with various stimuli, including Salmonella bacteria or LPS, leads to an activation state which provides for characteristic anchorage sites for the increased migration of LGL/NK cells towards

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb03127.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The question of whether there is a preferential use of certain V genes in T cells entering an inflamed joint has hitherto been studied mainly using unfractionated cells from synovial fluid and tissue respectively, and no clear answer to the question has yet been provided. Concomitantly. evidence has been provided that the use of V genes may differ considerably between CD4+ and CD8+ T cells, and consequently that detection of biased V‐gene expression within an inflammatory lesion may require separate analysis of the two T‐cell subsets.In this paper we have therefore studied T‐cell receptor V‐gene expression in rheumatoid arthritis by means of double stainings of synovial fluid and blood for available anti‐TCR monoclonal antibodies and antibodies to CD4 and CD8. respectively. Double stainings were also performed with anti‐TCR antibodies and antibodies to activation markers HLA‐DR and 1L‐2R. A certain bias towards the preferential use of certain V genes was seen particularly in the synovial fluid samples within both the CD4+ and CD8+ T‐cell populations, but no uniform pattern was evident among the 35 pati

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb03128.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

In this study, the mechanisms underlying stimulation of T‐cell proliferation by human blood dendritic cells (BDC) and their differentiation have been defined with a panel of monoclonal antibodies (MoAbs)‐ It was found that the MoAbs against LFA‐I (CDlla), CD11c. LFA‐3 (CD58), ICAM‐1 (CD54) or HLA‐DR could significantly suppress T‐cell proliferation in an allogeneic mixed lymphocyte reaction (P<0.05), while being unable to inhibit clustering of BDC with T cells. Addition of anti‐CD18 or CD45 MoAbs increased the size of clusters after 18 h of culture, but had no effect on the proliferation of T cells (P<0.05). The suppressive effect of the MoAbs may be viewed not as an inhibition of contact between BDC and T cells, but rather as a blocking of co‐stimulatory signals for T‐cell activation, which are mediated by interaction of the adhesion molecules. After depleting the BDC preparations of monocytes. we used a double staining in FACS analysis to demonstrate that BDC do not express specific T (CD3), B (CD20 and CD2l)and myeloid cell markers (CDl1b, CDl3 and CD14), but abundant class II antigens. This pattern remained unaltered after 8 days of culture in the presence of 100 U/ml GM‐CSF, although a threefold increase of HLA‐DQ and ICAM‐1 molecules on the cu

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb03129.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Nine monoclonal antibodies (MoAbs) were produced againsiMycobacterium bovisBCG aniigen 85 complex. Using isoelectric focusing combined with Western (immunoblot) blot analysis, antigenically related proteins could be identified in culture filtrates from M.tuberculosis, M. bovis. M. kansasii, M. aviumi, M. xenopi, M. gordonde, M. fortuitum, M. phlei M.smegmatis, Most of the MoAbs were found to be broadly cross‐reactive between the various mycobacterial species, albeit some minor differences were observed. These MoAbs reacted generally, in each species, with different components. One MoAb (VIDl‐14) was found to be specifically directed only against antigen 85B fromM. bovis. M. tuberculosis and M. kunsa

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb03130.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

We have determined the structure of the novel SAA gene. SAA4. The gene is 6.2 kb in length and comprises three introns and four exons. Introns 2 and 3 are significantly longer than those of the other human SAA genes. We have sequenced the exons and junction fragments and have shown that the sequence is the same as c‐SAA [1] and does not correspond to the pseudogene carried on GSAA4 [2]. The predicted SAA4 protein sequence has an eight amino acid insertion relative to the other human SAA proteins and is more closely related to rabbit and mouse SAA proteins than to the other human SAA proteins, or to those of animal species which also possess an insertion.We have analysed the predicted SAA4 protein relative to the other human SAA proteins and have identified three important structural regions. We predict that region 1 of SAA4 represents a lipid binding domain. Region 2 forms an extensive, distinetive, hydrophobic β sheet region in place of a helical region. In region 3, SAA4 is the only SAA protein having an α helix which is not amphipathic. We predict that the SAA4 protein retains a modified function of the conserved region, retains the Ca2+ binding site, has an amino terminal surface site and has a potentially distinct secretion pattern. Together, these differences indicate a distinct function from those of the other SAA prote

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb03131.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The main conclusions of this study are that BCG/PPD‐activated macrophages, in contrast to macrophages from control mice, exhibit an increased PMA‐induced production of H2O2. kill about one‐third of the phagocytosedCandida albicans, and cause more than 5O% inhibition of the intracellular formation of germ tubes by Calbicans. Peritoneal macrophages from mice that were colonized post‐natally with C.albicansdo not show increased produciion of H2O2: upon stimulation with PMA and the intracellular outgrowth of germ tubes is inhibited to only a limited degree. These macrophages are capable of killing about 2O% of the ingestedC, albicans. In vivo, the number ofCandidain the kidney, spleen and liver after intravenous injection ofCandida albicansis significantly lower in BCG‐treated mice than in control mice. Post‐natal colonization withC. albicanshas only a limited effect on the outgrowth of intravenously injectedC albicansthe spleen and liver but does not influence growth in the kidney. These results indicate that acquired immunity against a systemicCandidainfection involves both oxidative and nonoxidative mechanisms of intracellular killing and that these mechanisms may have different effects on the yeast and hyphal forms of

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb03132.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

The effect of disodium cromoglycate on in vitro proliferative responses of peripheral blood mononuclear cells from healthy individuals, allergic patients with moderate serum IgE and patients with atopic dermatitis and high levels of serum IgE was investigated. Peripheral blood mononuclear cells were stimulated with mitogens (phytohaemagglutinin, Concanavalin A), recombinant interleukin‐2, calcium ionophore+phorbol 12‐myristate 13‐acetate, purified protein derivative of tuberculin and allergens. It was possible to induce in vitro specific, allergentriggered responses only in allergic individuals with moderate serum IgE and not in individuals with atopic dermatitis and high serum IgE, Generally, whenever the stimulatory signal(s) caused a significant proliferative response, disodium cromoglycate inhibited the proliferation. This inhibition was seen for all activation agents and for both healthy and allergic individuals. By contrast, for certain non‐or low‐responders (both healthy and attergic individuals) disodium cromoglycate seemed to amplify the proliferation to various activation signals. Only non‐ or lowresponder cells derived from atopic dermatitis patients showed a biphasic kinetic response pattern when stimulated with the drug in combination with recombinant interleukin‐2, recombinant interleukin‐2+ ionophore or spe

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1992.tb03133.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY