摘要:

SummaryThe lineage relationship of dendritic cells with other haematopoietic cells and within the broader class of dendritic cells is not well understood. Dendritic cells in different tissue sites and having slightly different characteristics all play a specialized role in maintaining self tolerance by the endocytosis and presentation of antigens within their environment. Recent evidence now suggests a possible lineage relationship between T cells and lymphoid dendritic cells and appears to conflict with the view that dendritic cells have a common origin with myeloid cells. One possibility is that dendritic cells mature in different tissue sites from bone marrow‐derived precursors and develop region‐specific characteristics which could reflect lineage differen

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03407.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03408.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Oct2‐isoform expression in splenic B cells stimulated with lipopolysaccharide or lipopolysaccharide plus phorbol‐di‐butyrate was analysed by cDNA cloning. The frequency of Oct2‐positivc clones was 1/15, 000 in both libraries. Two new isoforms were found that generate novel amino‐ or carboxy‐terminal sequences. An isoform lacking exon 11 destroyed the carboxy‐terminal leucin‐zipper region and introduced a frame shift creating a novel, proline‐rich carboxy terminus. A new exon containing a highly basic region (4c) was characterized, between exons 4 and 5. This exon was inserted between glutamine‐rich regions 2 and 3, carboxy terminal of a tentative leucine‐zipper structure. In addition, a new combination isoform containing Oct2a's amino terminal insert (exon 7a) and Oct2b's carboxy terminal insert (exon 13) was found that created a novel large isoform, Oct2ab. More frequent use of the classical Oct2a and Oct2b isoforms was observed in the lipopolysaccharide‐stimulated B cells, while a preference for the Oct2ab and Oct2ba isoforms was observed in lipopolysaccharide plus phorbol‐

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03409.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Anti‐DNP antibody formation resulting from intraperitoneal (i. p.) immunization with DNP‐KLH may be blocked by simultaneous (i. p.) injection of DNP‐Ova or native Ova in mice orally tolerant to Ova, but not in normal mice. In Ova‐tolerant mice the inhibition of anti‐DNP antibody formation also occurred when DNP‐Ova and DNP‐KLH were given by separate routes of immunization: subcutaneous (s. c.) and i. p. A second exposure to Ova by gastric intubation (gavage) or intravenous administration simultaneously with i. p. immunization with DNP‐KLH failed to inhibit anti‐DNP antibody formation. There was inhibition of responses to DNP‐KLH i. p. by DNP‐Ova given 24 h before, but not 24 h after, and in the Ova‐tolerant mice, addition of DNP‐Ova only to the primary immunization with DNP‐KLH inhibited secondary and tertiary responses to DNP‐KLH in the absence of further exposures lo DNP‐Ova.These results suggest that the indirect effects of parenteral exposure of tolerant mice to the tolerated immunogen may inhibit unrelated immune responses. This inhibition is not due to ‘innocent bystanding’ suppression, i, e., to inhibitory cytokines provided locally by specific suppressor lymphocytes; it may derive from more dur

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03410.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

A shared amino‐acid sequence on the a helix of certain DRβ1 chains is predicted to generate a ‘shared epitope’ that is implicated in susceptibility to the development of rheumatoid arthritis (RA). Different relative risks (RR) for disease susceptibility and severity conferred by these DRβ31 chains suggest that their ‘shared epitopes’ are not equivalent. A set of monoclonal antibodies (MoAb) that map to the critical region, and for which optimal binding depends on DR context and cell lineage, was used to test this idea. Mapping experiments using mutated DRβ1* molecules showed that the antibody‐binding epitopes are overlapping; residue 70Q is pivotal for each, but neighbouring residues on the a helix and on the floor of the groove are also involved. Importantly, these epitopes are profoundly modified by peptide loading of DRβ31*0401 molecules. These data suggest that ‘shared epitopes’ on DR molecules that are associated with RA are influenced by their context; such structural modifications may be the basis for the varying susceptibilities conferred by these DR molecules for th

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03411.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

It is well known that the exposure of endothelial cells to IL‐1β induces an increase in endothelial cell adhesiveness for leucocytes. Using rat heart endothelial cells we found that exposure of endothelial cells to IL‐1β (100U/ml) induces a 133‐fold increase in the intracellular concentration of cyclic‐GMP; from 11.5×0.2fmto 1530 × 117.8 fm(per 106cells). Therefore, we examined whether cyclie‐GMP is involved in the regulation of endothelial adhesiveness for leucocytes. Cyclic‐GMP analogue, dibutyryl cyclic‐GMP (0.01–0.05mm), similarly to IL‐1β, increased endothelial cell adhesiveness for leucocytes. Methylene blue, an inhibitor of guanylate cyclase, and KT5823, a specific inhibitor of cyclic‐GMP‐dependent protein kinase, inhibited both basal as well as IL‐1β‐induced endothelial cell adhesiveness for leucocytes, and KT5823 abolished the dibutyryl‐cyclic‐GMP‐induced increase in endothelial adhesive ness. The effect of cyclic‐GMP, induced by IL‐1β treatment, on the endothelial adhesiveness may be either direct or indirect because of the time‐gap between the rise in cyclic‐GMP level and the increase of endothelial adhesiveness.IL‐1β (100 U/ml) and dibuthyryl‐cyclic‐GMP (0.01 mm) both induced an increase in the expression of intercellular adhesion molecule‐1 by endothelial cells. However, the fact that KT5823 failed to prevent this increase, suggests that, although the IL‐lγb‐induced increase in adhesiveness is caused by the increase in intracellular levels of cyclic‐GMP, it may not be mediated through intercellular adhesion molecule‐1.In conclusion, the results obtained indicate that endothelial cell adhesiveness for leucocytes is, in part, r

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03412.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Autoantibodies binding the 70K nRNP polypeptide are commonly found in the serum of patients with systemic lupus erythematosus. IgG antibodies binding overlapping octapeptides of 70K nRNP have been evaluated in 10 patients with anti‐nRNP precipitins, seven patients with other autoimmune serology, and four normal human sera. Neither normal controls nor patients without an anti‐nRNP precipitin significantly bind any of the 70K nRNP octapeptides. Sera containing an anti‐nRNP precipitin strongly bind various combinations of eleven different regions of the 70K nRNP protein. One antigenic region is consistently the most reactive in nine often nRNP precipitin positive sera tested. This sequence, KDKDRDRKRRSSRSR, is highly charged and has a similar pattern of alternating basic amino acids also present in seven of the other purported humoral autoimmune epitopes of the 70K nRNP polypeptide. The closely related DRKR and ERKR are important components of two of these epitopes. All regions of the 70K peptide bound by human anti‐nRNP precipitin positive sera are very rich in the basic amino acids., especially lysine (chi‐square = 23.03, odds ratio = 13.3,P<

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03413.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Coeliac disease (CD) is a T‐cell mediated immunological disease of the small intestine which is precipitated in susceptible individuals by ingestion of gluten. We recently reported that gliadin‐specific T cells can be found in the small intestinal mucosa of CD patients, and that a preponderance of these T cells was restricted by the CD‐associated DQ(%aL*0501, βl*0201)heterodimer. Here we report studies on whether the same is found for gliadin specific T cells in the peripheral blood of CD patients. T‐cell responses towards gluten antigensin vitrowere found for both most CD patients and healthy controls. Gluten‐specific T‐cell clones (TCC) were established from four CD patients. Although a large proportion of these TCC were restricted by DQ molecules, including the CD‐associated DQ(α1*0501, β1*0201) heterodimer, several were restricted instead by DR or DP molecules. Thus, gluten‐derived peptides can be presented to T cells by several different HLA elass‐II molecules, and the preferential DQ(#aL1*0501, β1*0201) restriction of gluten‐specific T cells in the small intestinal mucosa of CD patients is less pronounced than for similar T eells

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03414.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Multiple sclerosis (MS) may be an autoimmune disease, partially caused by autoreactivity to myelin basic protein (MBP) and other central nervous system proteins. Acute optic neuritis (ON) is a frequent first symptom of MS. The role of the HLA system in anti‐MBP antibody production in ON was investigated employing a restriction fragment length polymorphism system for genomic HLA‐DQ and ‐DR typing and an immunospot assay for the detection of individual cells secreting antibodies to three different synthetic MBP peptides. Thirty‐two out of 40 patients (80%) with ON had cells in cerebrospinal fluid secreting anti‐MBP peptide antibodies while this occurred in 10/19 patients with other neurological diseases (53%; mainly in patients with inflammatory diseases in the central nervous system). This difference was statistically significant (P= 0.03). None of the three examined peptides were immunodominant in any patient group. It was found, however, that presence of HLA DR15, which is associated with MS, may be associated further with predominant production of antibodies to the MBP amino acids 63–88 in patients with ON (P= 0.002, corrected for multiple c

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03415.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The Opsonophagocytic activity of the four human IgG subclasses was studied using chimeric mouse‐human antibodies with specificity for the hapten NIP. As target cells we used haptenized sheep red blood cells andN. meningitidis, labelled with different amounts of hapten. We used polymorphonuclcar leucocytes (PMN) as effector cells to measure respiratory burst (RB), and U937 to measure phagocytosis/rosette formation. When the target cells were opsonized with antibody only, and PMN used as effector cells, lgG3 was highly efficient, while IgG1 revealed an intermediate activity and IgG2 and IgG4 were negative. The same pattern among the subclasses was obtained in the presence of complement source, when target cells with low hapten concentration were used. However, at high cpitope concentration on the target cells, in the presence of complement source, IgG2 was highly active. while IgG4 was still negative or only slightly positive. When U937 were used as effector cells and complement was omitted, IgG1, IgG3 and lgG4 all revealed high phagocylic/rosette‐forming activity, while IgG2 was negative. When the target cells were opsonized with antibody and complement, the phagocytic/rosette‐forming activity was often suppressed. Our results reveal that all four human IgG subclasses possess Opsonophagocytic capacity, but with different requirements concerning complement and Fc Rs. They also enlighten us as to how IgG2 might perform its protective effect against harmful bacteria displaying high density of carbohydrate epitopes on their outside su

ISSN:0300-9475    

DOI:10.1111/j.1365-3083.1994.tb03416.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY