摘要:

AbstractUsing a cDNA subtraction technique, a novel member of the ubiquitin family was isolated from human dendritic cells. This gene encodes a diubiquitin protein containing tandem head to tail ubiquitin‐like domains, with the conservation of key functional residues. Expression of this 777‐bp mRNA was restricted to dendritic cells and B cells, with strong expression in mature B cells. Southern blot analysis indicated that a single copy of this gene is present.In situhybridization on tonsillar tissue showed expression in epithelial cells and isolated cells within the germinal center. With respect to an expressed‐sequence tag (EST) this cDNA could be localized to the major histocompatibility complex class I region of chromosome 6. Comparative analysis and the expression pattern of this gene suggests a function in antigen processing and present

ISSN:0014-2980    

DOI:10.1002/eji.1830271002

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractThe human HLA‐DQ8 (A1*0301/B1*0302) allelic product manifests a strong association with insulin‐dependent diabetes mellitus (IDDM). Previous biochemical studies of the major histocompatibility complex (MHC) class II I‐Ag7protein of IDDM‐prone non‐obese diabetic mice produced controversial results. To better define the biochemical properties of IDDM‐associated MHC class II molecules, we analyzed DQ8 proteins, in comparison to other DQ allelic products, by partially denaturing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS‐PAGE). We now report that DQ8 proteins have a normal peptide occupancy and lifespan in cells. Similar to I‐Ag7, DQ8 proteins formed only a minor fraction of SDS‐stable complexes with peptides. Although this phenotype was not unique to DQ8, some DQ allelic products such as IDDM‐protective DQ6 proteins were SDS resistant. The DQ9 allelic product, differing from DQ8 only at position (P) β57, was SDS stable, suggesting that non‐Asp residues at β57 might decrease the SDS stability of DQ proteins. We identified a single peptide which specifically induced an SDS‐stable conformation in DQ8 as well as in I‐Ag7molecules. The residues at anchor P1 in this peptide were found to influence the SDS stability of both molecules. Together with our previous observation of similar binding motifs of I‐Ag7and DQ8, these results demonstrate an overall biochemical similarity of mouse and human diabetes‐associated MHC class II molecules. This similarity might contribute to a common immunological me

ISSN:0014-2980    

DOI:10.1002/eji.1830271003

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractIn viral meningitis the inflammatory response involves activated T cells and monocytes which are recruited into the subarachnoid space. To identify the chemotactic signals attracting the cells to the site of infection in the meninges, we measured the levels of two CXC chemokines, interferon‐γ (IFN‐γ) inducible protein (IP)‐10 and monokine induced by IFN‐γ, four CC chemokines, monocyte chemotactic protein (MCP)‐1, RANTES, macrophage inflammatory protein (MIP)‐1α and MIP‐1β, as well as the cytokines interleukin (IL)‐15 and IL‐16 in the cerebrospinal fluid (CSF) of patients suffering from viral meningitis. The results point to an involvement of two chemokines, MCP‐1 and IP‐10, since (1) unlike the other cytokines, MCP‐1 and IP‐10 were present in 97 % and 79 % of the CSF, respectively, at concentrations sufficient to induce chemotaxis of mononuclear cells; (2) more than 90 % of the CSF of viral meningitis induced chemotaxis of peripheral blood mononuclear cells (PBMC) and all of them induced chemotaxis of activated T cells, and (3) the CSF‐mediated chemotaxis of PBMC was inhibited by anti‐MCP‐1 antibodies and chemotaxis of activated T cells was abolished by the combination of anti‐MCP‐1 and anti‐IP‐10 antibodies. Our data provide evidence that MCP‐1 and IP‐10 lead to accumulation of activated T cells and mono

ISSN:0014-2980    

DOI:10.1002/eji.1830271004

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractThe inoculation of antigens into the anterior chamber (AC) of the eye induces an antigen‐specific immune response that inhibits delayed‐type hypersensitivity (DTH). This regulatory response is known as anterior chamber‐associated immune deviation (ACAID). The ACAID response appears to be complex, as it can be elicited by a wide variety of soluble and cell‐associated antigens, including foreign, self, tumor, and alloantigens. To evaluate the contribution of Fas/Fas ligand (FasL) interaction to the induction of ACAID to alloantigens,gldandlprmutant mice were used in conjunction with normal C3H, MRL, and BALB/c mice. ACAID was induced by inoculation of non‐irradiated splenocytes from donor mice into the AC of various recipients. After 1 week, recipients were primed intradermally with donor splenocytes. One week later DTH was measured by ear swelling. C3Hgldmutants lacking functional FasL did not develop ACAID after the AC inoculation of BALB/c splenocytes. Conversely, the AC inoculation sensitized these mutants. MRLlprmutants, which lack Fas, developed ACAID following inoculation of BALB/c cells. AC inoculation oflprsplenocytes did not induce ACAID, but sensitized C3H recipients. Treatment of the AC inoculum with an anti‐Fas antibody blocked ACAID induction in a transient manner, as the recipients developed ACAID later. These results show that interaction of the Fas and FasL is required to induce ACAID to allogeneic cells. In the absence of Fas expression on donor splenocytes, or FasL expression by the recipient, AC inoculation primes for a DTH response rather than ind

ISSN:0014-2980    

DOI:10.1002/eji.1830271005

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractThe intracellular signaling pathways activated upon ligation of the co‐stimulatory receptor CD28 remain relatively ill‐defined, although CD28 ligation does result in the strong association with, and activation of, phosphatidylinositol (PI) 3‐kinase. The downstream effector targets of the CD28‐activated PI 3‐kinase‐dependent signaling pathway remain poorly defined, but recent evidence from other systems has shown that Akt/protein kinase B (PKB) is a major target of PI 3‐kinase and have indicated that a major function of PKB is the regulation of cell survival events. Given the strong coupling of CD28 to PI 3‐kinase and the known protective effects of both CD28 and PI 3‐kinase against apoptosis in different cell models, we investigated the effects of CD28 on PKB activation. We demonstrate that ligation of CD28 by either anti‐CD28 monoclonal antibodies or the natural ligand B7.1, results in the marked activation of PKB in both the leukemic T cell line Jurkat and freshly isolated human peripheral blood‐derived normal T lymphocytes. Our data suggest therefore, that PKB may be an important intracellular signal involved in CD28 signal transduction and demonstrate CD28 coupling to downstream elements of a signaling cascade known to

ISSN:0014-2980    

DOI:10.1002/eji.1830271006

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractAntibody(Ab)‐mediated inhibition of sporozoite invasion of hepatocytes is a mechanism that has been clearly demonstrated to act uponPlasmodium falciparumpre‐erythrocytic stages in humans. Consequently we have analyzed the Ab response to a recently identifiedP. falciparumsporozoite surface protein, STARP, in malaria‐exposed individuals and tested the inhibitory effect of these Ab upon hepatocyte invasionin vitro. STARP‐specific IgG were detected in 90 and 61 % of sera from regions where individuals were exposed to 100 and 1–5 infectious bites per year, respectively. These IgG were predominantly of the cytophilic IgG1 or IgG3 type. STARP and the major sporozoite surface protein, CS, elicited equivalent IgG levels in adults. When affinity purified from either African immune sera or the serum of an individual experimentally protected by irradiated sporozoite immunization, STARP‐specific Ab prevented up to 90% of sporozoites from invading human hepatocytes. The dose‐dependent and reproducible inhibition was more pronounced than that observed with human CS‐specific Ab affinity purified under identical conditions. Substantial reduction of sporozoite invasion was also observed with Ab induced by artificial immunization with recombinant STARP protein and reactive with the native protein. Taken together with recent findings of human cytotoxic T lymphocytes specific for this antigen, these results promote the interest of studying the efficacy of STARP as a target for immune effector mechanisms operating upon preeryt

ISSN:0014-2980    

DOI:10.1002/eji.1830271007

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractWe examined the effect of soluble IgG immune complex (IC) characteristics on the binding of IC to human neutrophils and IC‐induced specific granule release of neutrophils via Fcγ receptors (CD16 and CD32) and complement receptors (CR1 and CR3). A set of soluble IgG IC varying in size, IgG subclass, antigen epitope density and complement (C) incorporation were formed between 5‐iodo‐4‐hydroxy‐3‐nitrophenacetyl (NIP) coupled to bovine serum albumin (BSA) and chimeric mouse‐human anti‐NIP monoclonal antibodies (mAb) of all four IgG subclasses. High and low epitope density IC of all four IgG subclasses induced specific granule release with C, but in the absence of C only IgG1 and IgG3 IC were functionally active. The Fcγ and C receptors responsible for IgG IC‐induced specific granule release and IC binding were determined using mAb specific for the ligand binding sites of CD16, CD32 and CR3, and recombinant soluble CR1. Each defined IC displayed a unique pattern of receptor preference, dependent upon subclass and antigenic epitope density. IC binding and IC‐induced specific granule release was not mediated by the same receptor, or combination of receptors. High and low epitope density IgG3 IC binding and induction of specific granule release was mediated predominantly via CD16. Other IC subclasses bound differently,i.e.IgG1 IC used CD16 and CR3; IgG2 and IgG4 predominantly used complement receptors; but all three induced specific granule release via CD32.In vivothese results may translate into differential activation of neutrophils by soluble IC dependent upon their characteristics, leading to subtle nuances in the etiology, pathology and control of the immune response i

ISSN:0014-2980    

DOI:10.1002/eji.1830271008

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractThe heat‐stable antigen (HSA) is an important co‐stimulatory molecule on antigen‐presenting cells (APC). However, the receptor on T cells that receives the co‐stimulatory signal from HSA has not been identified. Because the HSA is transiently expressed on T cells after the T cell receptor/CD3 complex is engaged, and because it can bind to itself in a homotypic fashion, it has been proposed that homotypic interaction of HSA is responsible for its co‐stimulatory activity. Here we test this hypothesis using mice that have a targeted mutation of the HSA gene, as well as novel transgenic mice that constitutively express HSA on T cells. We show that HSA‐deficient T cells remain responsive to co‐stimulation by HSA. Furthermore, constitutive expression of HSA does not enhance T cell response to co‐stimulatory by HSA. Taken together, our results demonstrate that homotypic interaction of HSA is not responsible for co‐stimulation mediated by HSA

ISSN:0014-2980    

DOI:10.1002/eji.1830271009

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractZinc is a trace element which is essential for immune functions. It directly induces monokine secretion by monocytes; however, effects of zinc on T cells appear contradictory. Apart from enhanced lymphocyte proliferation in peripheral blood mononuclear cells (PBMC), inhibitory properties of high zinc dosages have also been described. In this study, PBMC failed to produce lymphokines like interferon (IFN)‐γ after stimulation with zinc in a serum‐ and LPS‐free cell culture system, whereas monokine secretion [interleukin (IL)‐1β] occurred. Zinc‐uptake studies with the zinc‐specific fluorescent probe zinquin revealed that zinc is taken up by PBMC within a few minutes, reaching nearly equal levels in PBMC, isolated monocytes, and T cells. However, if zinc was depleted 1 h after monocyte induction, zinc‐free pre‐cultured T cells were stimulated to secrete IFN‐γ by zinc‐induced monokines. Furthermore, the necessity for a cell‐cell interaction between monocytes and T cells for IFN‐γ induction was elucidated. Zinc ions inhibited the proliferation of the IL‐1‐dependent T cell line D 10N in a dose‐dependent manner, suggesting a direct inhibitory effect of zinc. By immunoprecipitation we revealed a specific inhibition of IL‐1 receptor‐associated protein kinase (IRAK) by zinc ions. Therefore, in contrast to an indirect stimulation of T cells due to zinc‐induced monokines, higher concentrations of zinc directly inhibit T cell functions by means of specific inhibition of IRAK and subsequent signaling events such as NFxB activation. The divergent effects of zinc on different cell populations, depending on the zinc concentration, could explain contradictory results of zinc stimulation. Furthermore, our data suggest new strategies of s

ISSN:0014-2980    

DOI:10.1002/eji.1830271010

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY

摘要:

AbstractMurine studies have demonstrated that, as with other nematodes, infection with the intestinal nematodeTrichinella spiralisis associated with a pronounced intestinal mastocytosis, eosinophilia and an elevation in serum levels of total IgE. Both interleukin (IL)‐4 and IL‐5 are clearly important in the generation of IgE responses and eosinophilia, respectively, but the control of mucosal mastocytosisin vivois not as well defined. Mucosal mast cells appear to be particularly important with regard toT.spiralisinfections as there is good evidence to suggest their involvement in expulsion of the parasite from the host. In this study we examined the effect of the overproduction of the Th2 cytokine IL‐9 on infection with this nematode. We demonstrate that naive IL‐9‐transgenic mice have an intense intestinal mastocytosis and high serum levels of mouse mast cell protease‐1. Moreover, upon infection high titers of parasite‐specific IgG1 were observed with a heightened mast cell response, which was associated with the rapid expulsion ofT. spiralisfrom the gut. Furthermore, as depression of this mast cell response, using anti‐c‐kitantibodies, resulted in the inability of these mice to expel the parasite, this study clearly demonstrates an activity of IL‐9 on mucosal mastocytosis and the host protective imm

ISSN:0014-2980    

DOI:10.1002/eji.1830271011

出版商:WILEY‐VCH Verlag GmbH    

年代:1997

数据来源: WILEY