bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kupffer cell depletionin vivoresults in clearance of large-sized IgA aggregates in rats by liver endothelial cells
Authors: BOGERS W M J M , STAD R K , JANSSEN D J , PRINS F A , VAN ROOIJEN N , VAN ES L A , DAHA M R 
Published: July 2010

SUMMARYWe investigated the clearance kinetics and tissue distribution of different sized IgA in normal and macrophage-depleted rats Rats were injected iv with liposomes containing dichloromethylene diphosphonate (DMDP). DMDP treatment resulted in complete depletion of liver macrophages 24-48 h after administration. Normal and macrophage depleted rats were injected intravenously with monomeric, dimeric, polymeric or aggregated polymeric IgA (AIgA) and assessed for blood clearance and tissue distribution. In normal rats, clearance of IgA was size dependent, i.e. a faster clearance with increasing size. No differences in clearance kinetics were observed of the different sized IgA between normal and DMDP-treated rats. TCA non-precipitable radioactivity, a measure for degradation of IgA, was found in the circulation of normal and DMDP-treated rats after AIgA administration. The liver was the main organ responsible for the clearance of IgA in normal and DMDP-treated rats. Immunofluorescence studies on liver biopsies indicated that AIgA was associated with Kupffer cells in normal rats. Electronmicroscopical studies revealed that the AIgA was internalized and located in vesicles in Kupffer cells. In DMDP-treated rats the AIgA was associated with endothelial cells and electron microscopy studies showed that this AIgA was taken up by endothelial cells. These data show that rat liver endothelial cells are able to bind, internalize and degrade AIgA in situations where Kupffer cells are absent, and that these cells may play an important role in the handling of AIgA and IgA-immune complexes.
T and B cell human responses to European bat lyssavirus after post-exposure rabies vaccination
Authors: HERZOG M , FRITZELL C , LAFAGE M , MONTAÑO HIROSE J A , SCOTT-ALGARA D , LAFON M 
Published: July 2010

SUMMARYT and B cell human responses lo European bat lyssavirus (EBL1) induced by post-exposure rabies vaccination (PM virus vaccine) were evaluated by measuring plasmatic titres of EBL1-specific neutralizing antibodies; specific EBL1-binding antibodies; and proliferation indices of peripheral blood lymphocytes stimulated in vitro with EBL1. These parameters for vaccination efficacy were compared with those obtained with vaccine-related viruses (CVS and ERA) and with a non-vaccine-related virus, Mokola virus, the last implicated in vaccination failures. Twenty-two patients exposed to rabies risk who received a reduced rabies post-exposure vaccination were involved in the study. On day 21, vaccine induced CVS-specific neutralizing antibodies in all patients; but EBL1-spccific neutralizing antibodies were induced in only 73% of patients. No vaccinee had Mokola-specific neutralizing antibodies. Patients having EBL1-specific neutralizing antibodies were usually those in whom vaccination induced high titres of CVS-specific neutralizing antibodies. On day 21, peripheral blood lymphocytes of 86% of patients could be restimulaled in vitro with vaccine, 43% with EBL1 and 45% with Mokola. Patients exhibiting a high vaccine-specific proliferation response more likely developed an EBL1-or a Mokola-specific proliferalive response. No correlation was found between T and B cell responses. Rabies vaccination induced neither T nor B cell EBL1-specific responses in 22% of patients.
Identification of cells responsible for the suppression of anti-beta-cell cytotoxicity in type I (insulin-dependent) diabetes mellitus
Authors: KRUG J , BIERWOLF B , LAMPETER E , VERLOHREN H-J , LOHMANN D 
Published: July 2010

SUMMARYPeripheral blood mononuclear cells (PBMC) from newly diagnosed type I diabetic patients induced a significantly higher cytotoxic insulin leakage from isolated rat islets during a 20-h incubation, compared with PBMC from healthy controls (13.9±7.7 versus 2.6±3.2 ng insulin/islet/20 h). The addition of PBMC from healthy subjects in a ratio of 1:4 suppressed the cytotoxic effect (13.9±7.7 to 6.7±4.4 ng insulin/islet/20 h). Depletion of CD8+ T lymphocytes from the PBMC of healthy subjects abolished their supprcssive capacity, while depletion of CD4+ T lymphocytes and pre-incubation with CD3 monoclonal antibodies had no effect.
Induction of cutaneousgraft-versus-hostdisease by local injection of unprimed T cells
Authors: KAWAI K , MATSUMOTO Y , WATANABE H , ITO M , FUJIWARA M 
Published: July 2010

SUMMARYThe skin is a major target organ in human graft-versus-host disease (GVHD) after bone-marrow transplantation. GVHD can be induced in mice by i.v. injection of T cells into unirradiated semi-allogeneic or lethatly irradiated allogeneic recipients. However, in the murine systemic GVHD model, cutaneous lesions occur only in lethally irradiated recipients. Since lethal irradiation itself might induce the epidermal cell damage, several investigators have employed another murine model of cutaneous GVHD, in which cutaneous lesions were induced by intradermal injection of alloreactive T cell clones. Using this system, it has been reported that both MHC class I- and II-reactive T cell clones can induce cutaneous GVHD in non-irradiated or sublethally irradiated recipients. However, it has remained unknown whether or not freshly prepared T cells are able to induce cutaneous GVHD after local injection into non-irradiated recipients. We show that unprimed T cells can induce cutaneous GVHD after local injection into unirradiated MHC class II- or I + II-disparate recipients. In contrast to alloreactive T cell clones, unprimed T cells could elicit only mild cutaneous lesions in MHC class I-disparate recipients. Since sublethal irradiation of MHC class I-disparate recipients did not result in the manifestation of cutaneous lesions after injection of unprimed T cells, host anti-donor responses by radiosensitive cells could not be responsible for this phenomenon. This experimental system provides a useful model for analysis of the regulation mechanisms in the induction of GVHD by unprimed T cells.
Expression of adhesion molecules in human intestinal graft-versus- host disease
Authors: NORTON J , SLOANE J P , AL-SAFFAR N , HASKARD D O 
Published: July 2010

SUMMARYThe distribution of three cellular adhesion molecules, ICAM-1. ELAM-1 and VCAM-1, was studied in normal rectal mucosa and in graft-Mrms-host disease (GvHD) using immunohistological and morphometric techniques. In normal controls, ICAM-1 was demonstrable on endothelial cells and leucocytes within the lamina propria, ELAM-I on endothelial cells only and VCAM-1 on lamina propria leucocytes, many of which exhibited long dendritic processes surrounding the glands. In GvHD, the enterocytes became positive for ICAM-1 and this was often associated with the presence of intra-epithelial LFA-1* lymphocytes and macrophages, ihe latter containing debris of apoptotic cells. The staining was. however, restricted to the luminal membrane of the epithelial cells, raising doubts about the role of ICAM-1 as a ligand for LFA-1 on mucosal leucocytes in rectal GvHD. ELAM-1 expression was increased in GvHD both in terms of the length of positive endothelium and staining intensity. VCAM-1 was increased on endothelial cells but not leucocytes in the lamina propria in contrast to our previous findings in cutaneous GvHD where VCAM-+ dendritic cells were increased and endothelial cells remained negative. Normal patterns of adhesion molecule staining were seen in two biopsies exhibiting no morphological evidence of GvHD, from patients who had strong clinical evidence of the disease, indicating that immunostaining for these molecules is unlikely to be of help in improving the sensitivity of histological diagnosis. However, the possibility that adhesion molecule staining may be useful in improving diagnostic specificity by helping to distinguish GvHD from identical histological changes produced by irradiation and cytotoxic drugs is worthy of further investigation.
Antibodies against C1q in anti-glomerular basement membrane nephritis
Authors: COREMANS I E M , DAHA M R , VAN DER VOORT E A M , MUIZERT Y , HALMA C , BREEDVELD F C 
Published: July 2010

SUMMARYThe prevalence of antibodies against the collagen-like region of the subcomponent of the first component of complement, Clq, was investigated in 11 patients with anti-glomerular basement membrane (GBM) nephritis. Anti-C1q antibodies (anti-ClqAb) were detected in seven patients. IgG anti-ClqAb were found in four and IgA anti-ClqAb in five patients. During follow up of the patients a relationship was observed between the levels of IgG anti-ClqAb and the levels of anti-GBM antibodies (anti-GBMAb). Gelfiltration experiments indicated that both IgG anti-ClqAb as well as IgG anti-GBMAb were monomeric and that binding also occurred with the F(ab′)2 fragments of the antibodies. Although anti-ClqAb and anti-GBMAb are both directed against a collagen-like structure, it was demonstrated by means of inhibition experiments that anti-ClqAb and anti-GBMAb are directed against different antigenic sites. Comparison of patients with anti-GBM nephritis with and without anti-ClqAb revealed that there were no differences in disease activity or disease severity. Therefore, the results of this study suggest that anti-ClqAb do not play a direct pathogenetic role in anti-GBM nephritis.
T and B cell responses following immunization with tetanus toxoid in IgA nephropathy
Authors: FORTUNE F , COURTEAU M , WILLIAMS D G , LEHNER T 
Published: July 2010

SUMMARYThe B and T cell responses were investigated in IgA nephropathy before and after immunization with tetanus toxoid (TT). Both IgA and IgG anti-tetanus toxoid antibodies were elicited, but the IgA ntibodies were significantly greater in patients (92·6 ± 11·7 ELISA units) than in the controls (49·2 ± 7·5 ELISA units). This was associated with a significantly greater proportion of IgA+ B cells in patients than controls before immunization. However, a significant increase in the proportion of IgA 1 binding CD4 and CD8 cells was also found. The proportion of CD3 cells with γδ T cell receptors (CD3+TCRγδ+), was significantly greater before immunization in the IgA nephropathy patients 37·0%± 2·4), compared with controls (100%± 2·3; P &lt; 0·001). Immunization with TT further enhanced the CD3+TCRγδ5+ cells in patients to 45·8%± 7·2 compared with controls (16·3%± 4·5), with a corresponding decrease in CD3+TCRαβ+ cells in the patients (P &lt; 0·001). CD3+TCRγδ+ cells are upregulated by common microbial antigens and clinical exacerbations of IgA nephropathy are frequently associated with mucosal infections and a rise in serum IgA concentration. The increased TCRγδ (5 expression may be responsible for the enhanced IgA antibody response in IgA nephropathy. The increase in IgA antibodies may then exert a controlling effect by binding to augmenting T cells and thereby inhibiting their function.
Autostimulatory effects of IL-6 on excessive B cell differentiation in patients with systemic lupus erythematosus: analysis of IL-6 production and IL-6R expression
Authors: KITANI A , HARA M , HIROSE T , HARIGAI M , SUZUKI K , KAWAKAMI M , AWAGUCHI Y K , HIDAK T , KAWAGOE A M , NAKAMURA H 
Published: July 2010

SUMMARYIntroducing avidin-biotin complex ELISA for anti-DNA antibody, the mechanism of in vitro production of anti-ssDNA antibody as well as of polyclonal immunoglobulin mediated by an IL-6-IL-6R loop was studied in patients with systemic lupus crythematosus (SLE). Regardless of the presence or absence of T cells, B cells from SLE patients could produce IgG anti-ssDN A antibody as well as total IgG without any stimulation. Low density B cells obtained by Percoll gradient density cenlrifugation responded to rIL-6 to produce IgG and IgG anti-ssDNA antibody. rIL-2 and rIL-4 had lesser effects on the differentiation of low density B cells. In fact, IL-6R was preferentially expressed on low density B cells from active SLE patients, as detected by anti-IL-6R MoAb, MT18, which did not inhibit IL-6 binding. SLE B cells, especially high density B cells, produced greater amounts of IL-6 in culture supernatants than did T cells, regardless of whether disease was active or inactive. Normal T cells and B cells did not produce significant amounts of IL-6. Thus, endogenous IL-6 produced by high density B cells bound to the IL-6R preferentially expressed on the low density B cells, and drove them into terminal differentiation, especially in active SLE patients. Further, addition of polyclonal anti-IL-6 or anti-IL-6R MoAb (PM1). which inhibited IL-6 binding, both inhibited IgG anti-ssDNA antibody as well as total IgG production by SLE B cells in a dose-dependent manner. These results suggest that interruption of the autocrine IL-6 loop would be of therapeutic value in SLE.
Bone marrow and peripheral blood natural killer cell activity in lymphomas. Its response to IL-2
Authors: CALDERA L H , LEON-PONTE M , ACQUATELLA G , BIANCO N E , BLANCA I 
Published: July 2010

SUMMARYNatural killer (NK) cytotoxic activity was simultaneously investigated in bone marrow mononuclear cells (BMMC) and peripheral blood lymphocytes (PBL) from nine Hodgkin's disease (HD) and 15 non-Hodgkin lymphoma (NHL) untreated patients. Twenty-five PBL samples and seven bone marrow specimens from healthy individuals were also included as control group (C). NK cell activity was evaluated in basal condition and post-stimulation with human recombinanl IL-2 (rIL-2). Data were expressed in K values (number of BMMC or PBL needed to lyse 50% of the target cells). In basal condition, both HD and NHL patients showed a NK cell activity comparable to the C group, both in BMMC (HD, K=2·48±1·3; NHL, K=3·8±2·0; C, K=3·2±0·7) and PBL (HD, K=2·0±1·0; NHL, K=2·3±1·0; C, K= 2·2±0·2). Stimulation with rIL-2 induced a significant and comparable enhancement of the NK activity in PBL from HD, NHL and C while the response to rIL-2 of the BMMC in most of the HD and NHL patients was significantly greater than the C group. Responder cells were characterized by negative selection with specific MoAb plus complement as a CD3−, CD16+, CD56+ cytotoxic cell and further confirmed by flow cytometry. We postulate that IL-2 activation of bone marrow NK cell precursors, in addition to enhancing the activity of circulating NK, may be of value for the therapeutic rationale of IL-2 in patients with lymphoma.
Heterogeneous effects of exogenous IL-2 on HIV-specific cell-mediated immunity (CMI)
Authors: BELL S J D , COOPER D A , KEMP B E , DOHERTY R R , PENNY R 
Published: July 2010

SUMMARYA characteristic feature associated with HIV-1 infection of the human host is a chronic decline in circulating CD4+ T helper/inducer cell numbers. Impaired cell-mediated immune functions usually occur in parallel with the decline in CD4+ T cells. Activated CD4+ T helper cells are a major source of endogenous IL-2 which is required for the immunoregulation of both antigen-specific B cells and CD8+ T cells. HIV-specific T cell proliferative responses are said to be weak and inconsistent, even during the asymptomatic phase of disease. We thus wished to determine how exogenous IL-2 affected HIV-specific T cell proliferation at different stages of the disease. Our cohort of 81 included both asymptomatic and symptomatic HIV-infected patients as well as uninfected normal donors. Proliferative responses of peripheral blood mononuclear cells (PBMC) that were elicited during culture with an immunodominant gp41-derived synthetic peptide, gp41{8}, and which were known to be CD8+ cell-associated in asymptomatics only, were used to analyse the effects of exogenous IL-2. IL-2 had three main effects on HIV-specific proliferation, namely (i) an additive effect, (ii) a synergistic effect, and (iii) an induced effect. More specifically, low dose exogenous IL-2 frequently augmented lymphoproliferation in both asymptomatic and symptomatic gp41{8} rcspondcrs. In most symptomatics, however, who were predominantly gp41{8} non-responders, exogenous IL-2 induced lymphoproliferation. Flow cytometric analyses using dual immunofluorescence were used to analyse the T cell subset distribution of proliferating PBMC cultures. During culture with gp41{8}, bothCD4+and CD8+ T cell numbers increased. However, after the addition of exogenous IL-2 to gp41{8}-containing cultures, CD8+ cell-associated lymphoproliferative responses were preferentially augmented. These results suggest that in symptomatics there is an inadequate supply of endogenous IL-2 to help maintain the strong and effective CD8+ cell-associated anti-viral immunity, and an exogenous supply of IL-2 may be required.
Activation of complement in normal serum by hydrogen peroxide and hydrogen peroxide-related oxygen radicals produced by activated neutrophils
Authors: SHINGU M , NONAKA S , NISHIMUKAI H , NOBUNAGA M , KITAMURA H , TOMO-OKA K 
Published: July 2010

SUMMARYNeutrophils activated by soluble partculate stimuli generate superoxide anion and subsequently form hydrogen peroxide and other oxygen radicals. The effect of hydrogen peroxide on the complement system in normal serum was investigated. Treatment of normal serum with hydrogen peroxide resulted in a diminution of the haemolytic activity of the total and alternative complement pathways and the haemolytic titres of C3 and C5 but not of C2, in normal serum. These decreases in complement activity depended on the concentration of hydrogen peroxide added to the serum. Immunoelectrophoretic analysis of hydrogen peroxide-treated serum showed that C3 and C5 proteins were activated. Complement degradation products C3a and C5a were produced in normal serum treated with hydrogen peroxide, and 20 mm EDTA abolished C3a and C5a production in hydrogen peroxide-treated serum but 20 mm Mg-EGTA did not. Catalase completely abolished and dimethylsulphoxide and D-mannitol, hydroxyl radical scavengers, partially inhibited the hydrogen peroxide-mediated complement activation. Hypochlorite, incubated with normal serum, significantly inhibited serum haemolytic activity, and sodium thiosulphate, a reducing agent, abolished the effect of hypochlorite. Normal serum incubated with activated neutrophils showed neutrophil chemotactic activity and decreased serum haemolytic activity, and the addition of catalase or methionine (S mm) completely abolished the effects of activated neutrophils. These results suggest that hydrogen peroxide activates complement via an alternative pathway of complement activation and that hydroxyl radicals and other hydrogen peroxide-related species such as hypochlorite are most likely involved in hydrogen peroxide-mediated complement activation. Complement activation by oxygen radicals produced by activated neutrophils may be one of the mechanisms by which complement is activated in human immune complex diseases.
Detection of cytokines at the site of tuberculin-induced delayed-type hypersensitivity in man
Authors: CHU C Q , FIELD M , ANDREW E , HASKARD D , FELDMANN M , MAINI R N 
Published: July 2010

SUMMARYCytokines are chiefly local mediators which play an important role in the regulation of the cell-cell interactions which may be involved in the development of the delayed-type hypersensitivity (DTH) reaction. Using immunohistochemical techniques, the presence of IL-la, IL-lβ, IL-6, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) in the skin in tuberculin-purified protein derivative (PPD)-induced DTH reactions was investigated in six normal individuals. Cells staining for these cytokines were first observed 6 h after PPD challenge, and they were detected throughout the duration of the 7-day experiment. The number of cells staining for IFN-γ reached a peak at 48 h. where 33% of the total aggregate cells were positive, but declined thereafter to 3% at day 7. On the other hand, the number of cells staining for TNF-α and IL-1 persisted at high levels throughout the observation period of 7 days (e.g. at 48 h and thereafter, about 40% cells positive for TNF-α and 20% for IL-la and IL-1β). Double immunofluorescence and staining on sequential sections showed that IFN-γ-staining cells were CD3+ T cells; TNF-α, IL-1 and IL-6 staining cells were mainly of the CD68* macrophages/monocytes and that 80% of the CDla4 cells (Langerhans-like cells) in the dermis contained TNF-α and IL-1. The presence of these cytokines at the site of inflammation suggests that they may be locally produced by the inflammatory cells. Their persistence during the reaction suggests that they are intimately associated with this response, and are involved in the development of the reaction.
Lymphocytes from patients with rheumatoid arthritis produce agalactosylated IgG in vitro
Authors: BODMAN K B , SUMAR N , MACKENZIE L E , ISENBERG D A , HAY F C , ROITT I M , LYDYARD P M 
Published: July 2010

SUMMARY
The percentage of oligosaccharide chains lacking galactose was measured in IgG obtained from pokeweed mitogen-activated cultures of blood lymphocytes from patients with rheumatoid arthritis and controls. Secreted IgG from rheumatoid arthritis lymphocytes was deficient in galactose compared with IgG from the lymphocytes of controls. This confirms that agalactosylation is a significant feature of the disease and demonstrates that it can occur at the B cell level and is not merely a post-secretory event.
Interferon-alpha and dexamethasone inhibit adhesion of T cells to endothelial cells and synovial cells
Authors: EGUCHI K , KAWAKAMI A , NAKASHIMA M , IDA H , SAKITO S , MATSUOKA N , TERADA K , SAKAI M , KAWABE Y , FUKUDA T , ISHIMARU T , KUROUJI K , FUJITA N , AOYAGI T , MAEDA K , NAGATAKI S 
Published: July 2010

SUMMARYWe investigated whether interferon-gamma (IFN-γ), interferon-alpha (IFN-α) and glucocorticoids affected the adhesion of T cells to human umbilical endothelial cells or human synovial cells. About 30% of peripheral blood T cells could bind to unstimulated endothelial cells, but only a few T cells could bind to unstimulaled synovial cells. When both endothelial cells and synovial cells were cultured with recombinant IFN-γ (rlFN-γ), the percentage of T cell binding to both types of cells increased in a dose-dependent manner. rIFN-α and dexamethasone blocked the T cell binding to unstimulated endothelial cells. Furthermore, rIFN-α and dexamethasone suppressed T cell binding to both endothelial cells and synovial cells stimulated by IKN-γ, and also inhibited intercellular adhesion molecule- l (ICAM-1) expression on both endothelial cells and synovial cells stimulated by 1 FN-γ. These results suggest that IFN-α and glucocorticoids may inhibit T cell binding to endothelial cells or synovial cells by modulating adhesion molecule expression on these cells.
In vivoclearance by the mononuclear phagocyte system in humans: an overview of methods and their interpretation
Authors: HALMA C , DAHA M R , VAN ES L A 
Published: July 2010

SUMMARYThe mononuclear phagocyte system (MPS) is responsible for the elimination of foreign material, effete autologous material and immune complexes. To study the relationship between MPS function and human disease, several test substances have been developed, and used to determine the clearance capacity of the MPS in human subjects in vivo. These test substances and the multitude of factors that influence the elimination of these substances (and complicate the interpretation of the test results) are discussed. Use of these probes bas provided important new insights, that may lead to the development of treatment modalities by which MPS function is modified in order to influence disease processes more effectively.