摘要:

The authors analysed cytokine production in hearts ofTrypanosoma cruzi‐infected CBA‐J mice byin situimmunocytochemical staining. Cellular infiltrates were recorded in hearts from both acute and chronic stages, but were not apparent in control hearts. In the acute heart, CD8 cells predominated, with associated production of IL‐4, IL‐6 and TNF‐α. Cytokine production was characterized by IL‐4, IL‐5, IL‐6 and TNF‐α in the chronic heart, and numbers of CD4 and CD8 cells were more equal. At this stage, calcified infarctions and associated fibrosis were apparent, mimicking chronic human Chagas' heart pathology. The authors consider the CBA mouse an appropriate model of chronicT. cruziinfection, and suggest that local cytokine production reflects establishment

ISSN:0300-9475    

DOI:10.1046/j.1365-3083.1996.d01-328.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

In this paper, the authors report the use of liquid‐liquid partition chromatography (LLPC) in an aqueous polyethylene glycol (PEG)/dextran two‐phase system to compare the surface properties (partition properties) of human antibodies and fragments thereof. The surface properties of all the monoclonal antibodies of different classes and subclasses investigated were within the same broad range as that observed for the polyclonal antibodies and no relationship was found between the exposed surfaces of the immunoglobulins (Ig) and their heavy chain isotype. Moreover, Fc fragments from various IgG1, 2 and 4 myeloma proteins were found to exhibit similar surface properties. Employing chimeric antibodies with identical variable regions the authors found that intact IgG1, 2 and 4 displayed identical surface properties, while the corresponding IgA1, IgA2, IgG3, IgE and IgM antibodies differed both from each other and from the IgGs. The surface properties of chimeric IgG3 could be made similar to those of the IgG1, 2 and 4 chimers by partially reducing the length of the hinge section, but new differences in surface properties appeared when their hinges were of similar length. Thus, LLPC can be used to detect differences or similarities in the surface properties of the antigen‐binding regions as well as the Fc part in the various isotypes. This can shed light on biological activities such as antigen binding and effector fun

ISSN:0300-9475    

DOI:10.1046/j.1365-3083.1996.d01-329.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Serum immunoglobulins reactive with several autoantigens have been reported to increase with age. The authors have studied the reactivity of serum immunoglobulins from mice between 2 and 24 months of age with antigens present in lysates of syngeneic tissue extracts from young mice. The profile of immunoglobulin binding with the immunoblots of spleen and brain tissue increased progressively with age, showing only minor differences from mouse to mouse and, with one exception, revealing that the age‐associated increase in binding of immunoglobulins occurred with antigens with the same migratory position in the immunoblots detectable, at lower concentration, in sera from young mice. Not all sera from older mice had increased immunoglobulin binding when tested with extracts of skin, muscle and liver but those that did expressed increased binding with antigens in all three lysates and with the same profile shown by sera from young mice. These results are consistent with the hypothesis that the age‐associated increase in autoreactive immunoglobulins represents a selective increase in autoreactive specificities expressed by serum immunoglobulins from young animals at lower lev

ISSN:0300-9475    

DOI:10.1046/j.1365-3083.1996.d01-335.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Anin vitromodel system has been developed in which freshly isolated resting WC1+γ/δTcR+T cells proliferate in response to cells transformed by the protozoan parasiteTheileria annulata, providing a strategy in which the basis of activation of naive γ/δ T cells can be investigated. Irradiated parasite‐transformed cells stimulate the proliferation, but not cytolytic activity, of autologous peripheral blood mononuclear cells (PBMC) from non‐immune animals. The proliferating cells are mainly WC1+γ/δ T cells. The majority of WC1+γ/δ T cells in freshly isolated PBMC express CD25 at a low level that increases when stimulated withT. annulata‐infected cells. Purified WC1+γ/δ T cells fail to proliferate when cultured with irradiatedT. annulata‐infected cells and produce a small proliferative response to IL‐2, but proliferate strongly to irradiated or lightly fixedTheileria‐infected cells in combination with IL–2. TheTheileria‐infected cells express cytokine transcripts encoding IL‐1α, IL‐1β, IL‐6 and IL‐10, but not IFNγ, IL‐2, IL‐4 and IL–7. Purified WC1+γ/δ T cells stimulated withT. annulata‐infected cells with or without IL‐2 fail to produce IL‐2 transcripts, but do produce those for TNFα. These experiments show that WC1+γ/δ T cells recognize a surface determinant onT. annulata‐infected cells, that together with a second signal, which can be pro

ISSN:0300-9475    

DOI:10.1046/j.1365-3083.1996.d01-332.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

Due to limitations in antigen processing, mice of the C57BL/10ScSn (B10) strain exhibit a low IgG production against a variety of T‐dependent antigens. To characterize the T‐cell functions, the authors studied antigen‐specific T‐cell proliferation and cytokine productionin vitro. The response of B10 mice was compared with that of the high IgG producing strain A/J. A highly restricted proliferative response and almost no interleukin‐2 (IL‐2) and interleukin‐3 (IL‐3) production was detected in lymph node (LN) cells of B10 mice primedin vivoby protein antigens and subjected to a specific restimulationin vitro, whilst A/J cells responded by significant proliferation and cytokine production. The antigen‐specific T‐cell response of B10 mice could not be increased by lipopolysaccharide treatmentin vivoor byin vitrocultivation with IL‐2. However, the T cells of B10 mice produced high levels of IL‐2 and IL‐4 when stimulated by phorbol myristate acetate (PMA) and Ca2+ionophore, proving the existence of a functionally intact signal transduction pathway downstream of protein kinase C (PKC). The results suggest that thein vivoantigen priming does not effectively activate the T cells in B10 mice. The limited activation consequently leads to the low IgG respo

ISSN:0300-9475    

DOI:10.1046/j.1365-3083.1996.d01-337.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

To leave the blood, leucocytes marginate to the vessel wall. Granulocytes thereby form the so‐called marginal pool. It is unclear to what extent such a second intravascular compartment also exists for lymphocyte subsets, NK‐cells and monocytes. Samples of the peripheral blood and the marginal pool of the LEW rat were analysed by flow cytometry. In the marginal pool the percentage of granulocytes and monocytes was significantly higher compared to that of the peripheral blood, and the proportion of ‘naive’ T and B lymphocytes was decreased. The expression of LFA‐1 was higher on all leucocyte subsets of the marginal pool except the granulocytes, whereas no differences were seen for the expression of other adhesion molecules (α4‐integrins, ICAM‐1, CD2, L‐selectin, and CD44). In addition, splenectomy influenced the cellular composition of peripheral blood and marginal pool differently and, after injection of blood leucocytes, these cells were found in both compartments showing its characteristic cellular composition. Thus, not only granulocytes, but also B and T lymphocyte subsets, NK‐cells and monocytes form a second distinct intravascular compartment. This marginal pool probably influences the cellular composition of leucocyte subsets available for entr

ISSN:0300-9475    

DOI:10.1046/j.1365-3083.1996.d01-334.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The immunological specificites of two human rheumatoid factor‐reactive IgG monoclonal antibodies derived from unstimulated rheumatoid synovial lymphocytes have been analysed. A malaria antigen‐reactive IgG monoclonal antibody from an immune donor served as a control. Purified IgG monoclonal antibody from one IgG‐RF hybridoma (L1), but not from the other IgG‐RF hybridoma (D1) or the anti‐malaria monoclonal antibody, exhibited dose‐dependent binding to multiple self and non‐self antigens such as ds‐DNA, cytochrome‐c, bovine thyroglobulin, transferrin, cellulose and lipopolysaccharide and therefore was considered polyreactive. The immunological specificity was confirmed by inhibition experiments using the same soluble antigens as inhibitors. The polyreactivity of the IgG‐RF MoAb was markedly inhibited by absorption with glycoproteins such as thyroglobulin, a commonly used target for xenoreactive natural antibodies, and cytochrome‐c, indicating that the monoclonal antibody is reactive with epitopes expressed on these ligands. Since some naturally occurring antibodies are carbohydrate specific, the authors tested the IgG‐RF MoAb for possible carbohydrate specificity. Absorption with certain polysaccharides containing only one or two different sugar moieties did not inhibit the binding reactivities to any of the tested antigens. Polyreactivity of the monoclonal antibody, unlike most xenoreactive natural antibodies, was not caused by reactivity with (galα1‐3gal) as indicated by the remaining binding reactivity after α‐galactosidase treatment of the antigen. Removal of the N‐linked glycosylation sites within the Fc portion of target IgG markedly reduced the antibody binding. The findings suggest that the carbohydrate content of the antigen is necessary for binding of the polyreactive IgG‐RF MoAb. Reactivity to carbohydrate antigens may readily explain the so‐called mul

ISSN:0300-9475    

DOI:10.1046/j.1365-3083.1996.d01-338.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

The induction of antibodies against peptides requires the presence of a T helper cell epitope. In the absence of an added T‐cell epitope only 10% of the mice, or less depending on the strain, gave an antibody response to a series of peptides of the measles virus (MV) fusion (F) protein. After co‐immunization with a non‐covalently coupled T‐cell epitope more than 60% of the peptides became immunogenic. Considerable differences became apparent when BALB/c mice were immunized with peptides in the presence of different T‐cell epitopes. An immunodominant T‐cell epitope of the MV‐F protein was more efficient than a subdominant or a cryptic T‐cell epitope in providing help to a non‐linked B‐cell epitope. There is both a ranking order of the amount of help which B‐cell epitopes require and a ranking order for the help T‐cell epitopes are able to provide. The capability of a T‐cell epitope to provide help to a B‐cell epitope correlated with its own immunogenicity, i.e. the intensity of the antibody response to the peptide representing the T‐cell epitope. The data suggest that for each MHC class II allele there is an optimal T‐cell epitope which can provide help to a maximal number of B‐cell epitopes and that such a peptide can be identified by its ability to induce antibodies against itself. By using this strategy, the authors were able to induce antibodie

ISSN:0300-9475    

DOI:10.1046/j.1365-3083.1996.d01-336.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

In a previous work the authors demonstrated that immunization withSchistosoma mansoni28‐kDa glutathion‐S‐transferase (Sm28GST) was able to reduce hepatic damage in infected mice and that the adoptive transfer of Sm28GST‐specific T cells reproduced the protective effect obtained with the recombinant molecule. In the present paper, the authors show that Sm28GST is also able to stimulate an antigen‐specific, cytotoxic T‐cell response against Sm28GST‐pulsed P815 target cells in normal mice and that effector cells inducedin vivowere classical Class I MHC‐restricted CD8+lymphocytes. The authors found no spontaneous CTL activity against Sm28GST‐pulsed target cells during the course of the infection byS. mansonialthough Sm28GST is expressed at different developmental stages of the parasite. It was observed, however, that immunization with Sm28GST is sufficient to elicit a significant level of CTL response for 6 weeks in infected mice. The role of these Class I MHC‐restricted CD8+lymphocytes in the protection observed precisely at the same period in immunized mice remains to be elucidated. The authors also observe that immunization with the lipopeptidic form of the C‐terminal peptide of the molecule (190–211 peptide) led to a CTL activation comparable to that observed after immunization with the whole molecule demonstrating the feasibility of using a synthetic lipopeptide as immunogen for a CTL response against Sm28GST epitopes. Moreover, like Sm28GST‐specific CTLs, 190–211 lipopeptide‐specific cells were also Class

ISSN:0300-9475    

DOI:10.1046/j.1365-3083.1996.d01-340.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY

摘要:

‘Acute phase’ and ‘constitutive’ SAA (A‐SAA and C‐SAA, respectively) mRNA levels were measured in hepatic and non‐hepatic cell lines after treatment with monocyte conditioned medium (MoCM), with or without dexamethasone (Dex). A‐SAA mRNAs were detected in MoCM‐treated hepatoma cell lines (PLC/PRF/5, HuH7, HepG2, and Hep3B), a fibroblast cell line (MRC5), six epithelial cell lines (RT4/31, SW13, Hela Ohio, HCT‐8, CaCo2, and KB), and an endothelial cell line ECV304. In KB cells, Dex alone caused a dramatic increase in A‐SAA mRNA levels. C‐SAA was detected in all hepatic and non‐hepatic cell lines. Two differentially regulated size classes of C‐SAA mRNA were detected in the hepatoma cell lines. A‐SAA mRNA levels were measured in ECV304 cells treated with IL‐1β, IL‐6, TNFα and Dex, in various combinations, and revealed different profiles to those seen for hepatic cells. The extent of polyadenylation of A‐SAA mRNA in ECV304 and KB cells differed whereas the polyadenylation of C‐SAA mRNA remained constant. These data suggest that the parameters that determine the steady state mRNA levels and post‐transcriptional regulation of A‐SAA and C‐SAA m

ISSN:0300-9475    

DOI:10.1046/j.1365-3083.1996.d01-341.x

出版商:Blackwell Science Ltd    

年代:1996

数据来源: WILEY