摘要:

AbstractTwo T suppressor (Ts) clones of different specificity have been analyzed for their lymphokine spectrum. BVI/5 is an I‐Ek‐restricted bovine serum albumin (BSA)‐specific Tscell clone from a CBA/J mouse tolerized by low doses of BSA. It affects directly or indirectly the function of BSA‐specific T helper (Th) cells. The Tscell clone 178‐4 from a BALB/c mouse is I‐Edrestricted and recognizes the public J558 Id on B cells. It prevents α(1→3)dextran B 1355S (Dex)‐specific IgG antibody production and drives Dex‐specific J558 idiotype‐bearing B cells into an anergic B IgG memory cell state. Both Tscell clones thus cause specific suppression, yet in different experimental systems using different effector mechanisms. Upon stimulation with concanavalin A or fixed CD3‐specific monoclonal antibody, both clones produce high levels of interferon (IFN)‐γ and tumor necrosis factor (TNF) but in contrast to Th1 cells no interleukin (IL)‐2. Both clones produce low levels of IL‐3 and IL‐6 but no IL‐4, IL‐5 and IL‐9. Furthermore, unlike Th2 cells, both clones do not respond to IL‐1. The mechanism of the idiotype‐specific induction of anergy in Dex‐specific B IgG memory cells by 178‐4 Tscells is not yet understood. BVI/5 Tscells suppressin vitrothe BSA‐specific proliferation of the BSA‐specific Thcell clone 83/1, as well as the response of BSA‐primed CBA/ LN cells. Whereas the suppressive effect on 83/1 cells is due to IFN‐γ alone the suppression of BSA‐specific lymph node cells can be simulated neither by IFN‐γ nor the combination of IFN‐γ and TNF. Thus these mediators cannot account for the antigen‐specific suppression by BVI/5 Tscells in polyclonalin vitroresponses from lymph node ce

ISSN:0014-2980    

DOI:10.1002/eji.1830220802

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractInjection of A/J splenocytes (H‐2Dd, Mlsc) into unirradiated (A/J x CBA)F1(BAF1) host mice (H‐2Dd/k, Mlsd) results in an acute suppressive graft‐vs. ‐host reaction (GVHR), characterized by immune dysfunction and appreciable donor cell engraftment; injection of the CBA/J parent (H‐2Dk, Mlsd), which recognizes no Mls disparity in the host, results in little or no GVHR. Furthermore, the Mlsa‐reactive Vβ6and Vβ8.1T cell subsets in A/J T cells expand significantly in the GVHR host. Finally, depletion of Vβ6+ and Vβ8.1+ from the A/J population abrogates the proliferative response to BAF1in vitroand the development of GVHRin vivo.Thus, the response to Mls determinants can contribute to the gener

ISSN:0014-2980    

DOI:10.1002/eji.1830220803

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractPrevious studies demonstrated that mannan is a potent inhibitor of splenic entry of lymphocytes and mediates its inhibitory effect at an unidentified site in the spleen rather than acting directly on lymphocytes. This report describes thein vivosite of action of mannan.In vivolocalization studies with fluoresceinated preparations of mannan (Fl‐mannan) and a mannose‐6‐phosphate‐containing yeast phosphomannan monoester core fromP. holstiiexopolysaccharide (Fl‐PPME) demonstrated that the polysaccharide specifically localize in the splenic marginal sinuses in cells with a dendritic morphology termed splenic sinusoidal cells (SSC). Uptake of the polysaccharides by SSC was mediated by a mannan‐specific receptor which was saturable and of high avidity. Several lines of evidence suggested that mannan uptake by SSC inhibited splenic entry of lymphocytes. First, the ability of SSC to bind Fl‐mannan and Fl‐PPME closely paralleled the ability of these polysaccharides to inhibit splenic entry of lymphocytes. In fact, doses of mannan and PPME which would saturate SSC mannan receptors completely blocked splenic entry of lymphocytes. Second, SSC are situated at the initial entry point of lymphocytes into spleen and passage of lymphocytes through the SSC region of spleen was profoundly inhibited by mannan. Finally, direct evidence for adhesion between lymphocytes and SSC was obtained with spleen cell suspensions where clustering between Fl‐mannan labeled SSC and lymphocytes was observed. Collectively, these data indicate that mannan (and PPME) inhibit splenic entry of lymphocytes by interacting with SSC, cell which play a critical role in the entry of lymphocytes into the spleen. Whether mannan‐specific receptors on SSC directly mediate lymphocyte‐SSC adhesion or play on indirect role in modifying lymphocyte migration requires

ISSN:0014-2980    

DOI:10.1002/eji.1830220804

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractA simple, cost‐effective method is described that allows rapid screening of recombinant protein sequences for their ability to stimulate T cells. Individual microcultures ofE. colieach expressing a gene product or peptide sequence fused to protein A are grown in 96‐well plates. Following lysis of the bacteria, the fusion peptide is readily captured with immobilized immunoglobulin in tissue culture wells. No further purification is required. T lymphocytes plus appropriate antigen‐presenting cells are added directly to the wells and assayed for proliferation. The DNA in bacteria from wells stimulating T cell proliferation is then sequenced. The technique allows rapid mapping of T cell epitopes by facilitating screening of truncation mutants without extensive purification. Described here is a further application of the technique to study monosubstituted analogues of a known T cell ep

ISSN:0014-2980    

DOI:10.1002/eji.1830220805

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractMyeloma is one of the interleukin (IL)‐6‐related diseases to which abnormal expression of IL‐6 has been reported to be linked. We examined thein vivoinhibitory effect of anti‐human IL‐6 receptor (IL‐6R) antibody on human myeloma cell growth in mice. SCID mice were subcutaneously inoculated with solid tumor of the myeloma cell line S6B45 in which human IL‐6 was acting as an autocrine growth factor. Ten intraperitoneal administrations of 100 μg of the anti‐human IL‐6R antibody PM1 at 48‐h intervals strongly inhibited the growth of S6B45 cells when the administration started 24 h after tumor inoculation. The tumor growth inhibitionin vivowas also observed by administration of the anti‐human IL‐6 antibody MH166 using the same procedure as for PM1. The inhibitory effect of PM1 was not significant when the administration started 5 or more days after tumor inoculation. This work indicates that anti‐human IL‐6R antibody, as well as anti‐human IL‐6 antibody inhibits human myeloma growthin vivo, and provides an animal model for testing the therapeutic value of agents such as antibodies to human IL‐6, IL‐6R and gp130, an IL‐6R‐associated signal transd

ISSN:0014-2980    

DOI:10.1002/eji.1830220806

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractRecently, we reported preliminary evidence for the induction of tolerancein vivoby cyclosporin A (CSA) during a persistent virus infection in rats. In the present communication, those observations are verified and the findings extended to the functional level of cell‐mediated immunity. Mice infected intracerebrally with lymphocytic choriomeningitis virus (LCMV) normally die from a fatal immunemediated disease after 6–8 days but they do not succumb if treated intraperitoneally with 50 mg/kg/day of CSA. Immunosuppression initiated one day before infection and continued for at least two consecutive weeks resulted in the absence of immunopathologic disease of the brain and in the survival of mice, which were found to be persistently infected virus carriers. In these animals, no cytotoxic T cell activity could be detected. The effect of CSA was not due to a toxic effect on the immune response since immune reactivity was restored as early as 4 days after discontinuation of the drug in control animals. Neither secondaryin vitronorin vivorestimulation resulted in the generation of a cellular antiviral immune response. Cytotoxic T cell reactivity to third‐party antigen, however, could be detected, although somewhat delayed. Additionally, spleen cells from CSA‐treated mice did not clear the virus from LCMV‐infected recipients upon adoptive transfer, whereas spleen cells from LCMV immune mice completely eliminated virus infection in carrier mice. However, mice immunosuppressed with CSA and infected with vesicular stomatitis virus (VSV) did not generate a primary immune response but were immunologically fully reactive to challenge infection, providing evidence for the absence of tolerance and the presence of antigen‐specific temporal unresponsiveness. Thus, as exemplified by VSV infection in which the virus does not replicate to considerable titers in mice and viral antigens do not persist, the presence of the foreign antigen for prolonged periods of time could be shown to be aconditio sine qua nonfor CSA‐indu

ISSN:0014-2980    

DOI:10.1002/eji.1830220807

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractCastanospermine (CSP), an inhibitor of α‐glucosidase, enhanced immunoglobulin (Ig) release in aStaphylococcus aureusCowan I (SAC)‐induced lymphocyte culture (Scand. J. Immunol.1990.32: 529). In a pokeweed mitogen (PWM)‐human lymphocyte culture, unlike the SAC‐stimulated system. CSP strongly decreased the number of IgG‐, IgA‐ and IgM‐secreting cells as well as that of Ig‐bearing cells. Peripheral blood lymphocytes treated with swainsonine, a mannosidase II inhibitor, or with neuraminidase also showed a reduced response to PWM. In cross‐culture experiments, only a mixture of B cells pretreated with either agent and untreated T cells showed such a suppressive effect. Adhesion was decreased between B cells treated with either agent and untreated T cells, but not between treated T cells and untreated B cells. These results demonstrate that a certain alteration in B cell membrane oligosaccharides inhibited the T cell‐B cell adhesion in the PWM culture, leading to an arrest of B cell maturation. Considering that these inhibitors eventually prevent terminal sialic acid addition, the present study provides evidence that sialic acids on B cell surface oligosaccharides play a biological role in the T cel

ISSN:0014-2980    

DOI:10.1002/eji.1830220808

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractThe mechanism of immunodominance was investigated using chimeric peptides from mouse myelin basic protein consisting of the immunodominant I‐Au‐restricted Ac1‐11, attached by a peptide bond to I‐Eu‐restricted 35–47. Our results indicate that this chimeric peptide and certain of its derivatives were excellent immunogens bothin vitroandin vivo.Notably, on immunization with Acl‐11:35–47 or Ac1‐11 (Ala4):35–47, the proliferative T cell responses to each of its component peptides were almost completely “subjugated” in favor of neo‐determinants that are I‐Eurestricted. Furthermore, each of 11 hybridomas derived after immunization with Ac1‐11:35–47 had specificity for junctional neo‐determinants and none could be stimulated to produce interleukin‐2 from Ac1‐11 or 35–47. Subjugation of the immunogenicity of the original determinants occurred regardless of their dominance when separate. It did not appear to result from non‐availability of the original determinants because the chimeric peptide was able to induce neonatal tolerance to each of its constituents. These results indicate that in an overlapping multideterminant array, the dominant determinant is unpredictable from historical data about any of the components. Determinant choice, at any stage of processing, may be governed by competitive aspects of determinant capture in an environment where all components ‐antigen, major histocompatibility

ISSN:0014-2980    

DOI:10.1002/eji.1830220809

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractType 1, insulin‐dependent diabetes mellitus (IDDM) appears to result from a T cell‐dependent destruction of insulin‐producing pancreatic β cells. In non‐obese diabetic (NOD) mice and in other rodent models of human IDDM, final expression of disease may be controlled by protective, as well as, destructive T cell influences. Previously, a CD8+T cell clone, I.S. 2.15, was isolated directly from islets of disease‐resistant male NOD mice. Upon transfer to young NOD recipients, the non‐cytolytic I.S. 21.5 T cell clone, confersin vivoprotection from two forms of accelerated IDDM. The present study demonstrates that I.S. 2.15 T cells inducein vitroimmunosuppression. The suppressive effects of I.S. 2.15 T cells are mediated through soluble factor(s) and are independent of T cell activation, cell contact, antigen specificity or the major histocompatibility complex (MHC). By polymerase chain reaction (PCR), I.S. 2.15 T cells contain mRNA species encoding for the potentially immunosuppressive cytokines, interleukin‐10 (IL‐10) and transforming growth factor‐β (TGF‐β). The T cell suppressive effects engendered by I.S. 2.15 T cells closely mimic those observed with TGF‐β. Moreover, I.S. 2.15‐induced immunosuppression correlates with intracellular levels of TGF‐β mRNA. These results establish that immunoregulatory T cells are present within islets in IDDM‐resistant NOD mice and may impact on final disease expression through the p

ISSN:0014-2980    

DOI:10.1002/eji.1830220810

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY

摘要:

AbstractThe knowledge about the differentiation of basophilic leukocytes is fragmentary. This report discusses a detailed phenotypic characterization of molecular markers for hematopoietic differentiation in a basophilic leukemia cell line, KU812. The expression of markers for lymphoid, erythroid, neutrophil, eosinophil, monocytic, megakaryocytic, mast cell and basophil differentiation was analyzed at the mRNA level by Northern blots in the KU812 cells, and for reference, in a panel of human cell lines representative of the different hematopoietic differentiation lineages. KU812 was found to express a number of mast cell and basophil‐related proteins,i.e.mast cell tryptase, mast cell carboxypeptidase A, high‐affinity immunoglobulin (IgE) receptor α and γ chains and the core protein for heparin and chondroitin sulphate synthesis. We found no expression of a number of monocyte/‐macrophage or neutrophil leukocyte markers except for lysozyme. From earlier studies, it has been shown that lysozyme is not expressed in murine mucosal mast cell lines. This finding, together with the expression of the mast cell carboxypeptidase in KU812 might distunguish the phenotype of this cell line from that typical of mucosal mast cell lines in rodents. We found a low level of expression of the eosinophil and basophil marker, major basic protein, which might indicate a relationship between basophils and eosinophils. No expression is, however, detected with the eosinophil‐specific markers eosinophil cationic protein, eosinophil‐derived neurotoxin or eosinophil peroxidase.We also report an extensive screening for inducers of basophilic differentiation of the KU812 cells. The most efficient protocol of induction included serum starvation which led to a dramatic increase in a number of markers specific for mast cells and basophils such as tryptase, carboxypeptidase A and the heparin core protein.Finally, diisopropylfluorophosphate analysis of total protein extracts from KU812 show four labeled protein bands with sodium dodecyl sulfate‐polyacryl‐amide gel electrophoresis, indicating that this cell line expresses at least three previously undescribed serine proteases of which one or more could be a potential basophil‐s

ISSN:0014-2980    

DOI:10.1002/eji.1830220811

出版商:WILEY‐VCH Verlag GmbH    

年代:1992

数据来源: WILEY