bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of cytokine gene expression in CD4+ and CD8+ T cells after activation with phorbol myristate acetate and phytohaemagglutinin
Authors: LEUNG J C K , LAI C K W , CHUI Y L , HO R T H , CHAN C H S , LAI K N 
Published: July 2010

SUMMARYCytokinesare important mediators involved in the development of effector cells and in the regulation of immune responses. The gene expression of these mediators in T cell subset has yet to be fully elucidated. Using sensitive reverse transcription-polymerasc chain reaction (RT-PCR). the kinetics of cytokine gene expression in human CD4+ and CD8+ T cells were examined. CD4+ T cells were more readily activated by phorbol myrislatc acetate (PMA) and phytohaemagglutinin (PHA) than CD8+ T cells in terms of the IL-2 receptor (IL-2R) mRNA expression. Quantitative differences in cytokine gene expression between CD4+ and CD8+ T cells were confirmed and higher levels of cytokine mRNAs were induced in CD4+ than in CD8+ T cells. Early induction of IL-2 mRNA was observed in both T cell subsets. The demonstration of diffcrenl kinetics of cytokine gene expression illustrates one of the examples of the complexity of immunoregulation. The differential response of cytokine gene expression in different T cell subsets should be taken into consideration when clinical studies in cytokine production by peripheral blood mononuclcar cells arc interpreted.
Interference of Wegener's granulomatosis autoantibodies with neutrophil Proteinase 3 activity
Authors: van de WIEL B A , DOLMAN K M , van der MEER-GERRITSEN C H , HACK C E , von dem BORNE A E G Kr , GOLDSCHMEDING R 
Published: July 2010

SUMMARY
Classic anti-neutrophil cytoplasmic autoantibodies (C-ANCA) are disease-specific markers of Wegener's granulomatosis (WG). The possible pathogenetic role of these autoantibodies, which are directed against Proteinase 3 (PR3), is not yet clear. We studied the effect of C-ANCA on PR3 proteolytic activity and on the complcxation of PR3 with alpha1-antitrypsin (α1AT). C-ANCA IgG from eight patients with active WG significantly inhibited PR3 proteolytic activity, particularly towards elastin (median 84.2% inhibition). C-ANCA IgG significantly inhibited the complexation of PR3 with α1AT (median 58.8% inhibition). Moreover, addition of purified PR3 to C-ANCA-positive sera from WG patients yielded less complexes with α1AT (median 44.8%) compared with sera containing perinuclear anti-neutrophil cytoplasmic autoantibodies (P-ANCA) or ANCA-negative sera. These findings indicate the existence of a hitherto unknown property of C-ANCA, which may be of importance in the pathogenesis of WG.
The B cell repertoire in patients with systemic autoimmune diseases: analysis of Epstein-Barr virus (EBV)-inducible circulating precursors that produce autoantibodies against nuclear ribonucleoprotein (nRNP)
Authors: OKAWA-TAKATSUJI M , AOTSUKA S , UWATOKO S , SUMIYA M , YOKOHARI R 
Published: July 2010

SUMMARYPeripheral blood B cells from patients with systemic autoimmune disease and healthy volunteers were immortalized using EBV and the frequencies of B cell precursors that produced immunoglobulin class-specific antibodies against anti-nRNP, a specific marker for mixed connective tissue disease, were assessed using limiting dilution analysis. The frequencies of EBV-induced B cell precursors that produced IgG anti-nRNP were correlated closely with the serum titres of the corresponding autoantibodies, which indicates that B cell precursors that produced potentially pathogenic autoantibodies could be immortalized from the peripheral blood of the patients by EBV. In contrast, the frequency of EBV-induced B cell precursors that produced IgM anti-nRNP in patients with systemic autoimmune disease was comparable to that in healthy volunteers and greater than those that produced IgG and IgA anti-nRNP. Moreover, many of the clones that produced IgM antibodies against nRNP reacted with other autoantigens, such as double-stranded DNA, single-stranded DNA and rabbit IgG. These polyreactive IgM antibodies are believed to belong to the ‘natural antibodies’, to be coded by the germline immunoglobulin V genes, and to react with evolutionarily conserved structural cellular components, including nRNP. Our finding that nRNP is one of the target antigens for this polyreactive autoantibody may lead to the elucidation of the origin of the pathogenic IgG and IgA anti-nRNP antibodies found in sera from patients with systemic autoimmune diseases.
Fibroblast growth factors in connective tissue disease associated interstitial lung disease
Authors: THORNTON S C , ROBBINS J M , PENNY R , BREIT S N 
Published: July 2010

SUMMARYFibrosis is a major cause of morbidity and mortality in chronic inflammatory diseases, especially interstitial pulmonary disorders. Fibroproliferation is an important part of this fibrotic response, and is mediated largely through growth factors such as platelet-derived growth factor (PDGF), insulin-like growth factor (IGF) I and tumour necrosis factor-alpha (TNF-α). Although there is some evidence implicating these cylokines in fibrotic disorders, strong evidence in vivo is almost nonexistent. In order to ascertain the role that these factors play in inflammatory lung disorders associated with connective tissue diseases, alveolar mononuclcar cells have been obtained from subjects by bronchoalveolar lavage and assessed for the spontaneous release of fibroblast growth factors. The study population consisted of subjects with a variety of different connective tissue disorders, both with and without inflammatory pulmonary complications. It was found that lavage cells spontaneously secreted fibroblast growth factor activity over 24 h with maximum activity detected at 6 to 12 h. Growth factor activity could be detected in most subjects with connective tissue disease-associated inflammatory lung disease and some normal subjects, but the amount of growth factor activity was much higher in the former than in the latter. By means of antibody depletion experiments all growth factor activity from lavage cells of normal patients was attributable to TNF-α while patients with interstitial lung disease secreted large amounts of PDGF and fibronectin in addition to TNF-α. Approximately 40–50% of the total released growth factor activity could be accounted for by PDGF, and 100% by the combination of PDGF. TNF-α and fibronectin. While TNF-α is released from the bronchoalveolar lavage cells of many subjects, in addition, many patients with interstitial lung disease also release spontaneously, large amounts of fibroblast growth factor activity attributable to PDGF and fibronectin.
MRL/lpr→ severe combined immunodeficiency mouse allografts produce autoantibodies, acute graft-versus-host disease or a wasting syndrome depending on the source of cells
Authors: ASHANY D , HINES J J , GHARAVI A E , MOURADIAN J , DRAPPA J , ELKON K B 
Published: July 2010

SUMMARYMRL/lpr (lpr) mice spontaneously develop a lupus-like illness as well as massive lymphadenopathy. Attempts to transfer autoimmunity by adoptive transfer or radiation bone marrow chimeras have been unsuccessful. Since severe combined immunodeficiency (SCID) mice have been engrafted with human and rat xenografts without apparent grafl-versus-host disease (GVHD), we subjected SCID mice to low-dose irradiation and reconstituted the mice with spleen cells from young or oldlpr mice or withlpr bone marrow. Fourteen out of twenty (70%) of SCID mice engrafted with spleen cells from oldlpr mice produced autoantibodies (anti-DNA and anti-Sm) without evidence of the severe lymphoid atrophy previously described forlpr spleen +/+chimeras. SCID mice engrafted with spleen cells from younglpr mice developed acute GVHD and 5/6 (83%) died within 4 weeks post-transfer. Although 8/11 (73%) of lpr→ SCID bone marrow allografts survived for at least 4 months, these mice developed a wasting disease characterized by lymphoid atrophy and fibrosis without the production of autoantibodies. None of the lpr→ SCID grafts resulted in the transfer of double negative T cells or the lymphoproliferative syndrome characteristic of MRL/lpr mice. These findings indicate that SCID mice can be engrafted with splenocytes from old MRL/lpr mice and that B cells continue to secrete autoanlibodies for several months in the SCID recipients. This study also demonstrates that, unlike i.p. transplant of xenogeneic cells, acute GVHD is a consistent feature of i.p. transplants of normal allogeneic mononuclear cells into SCID mice.
Anti-neutrophil cytoplasmic autoantibodies in patients with symptomatic HIV infection
Authors: KLAASSEN R J L , GOLDSCHMEDING R , DOLMAN K M , VLEKKE A B J , WEIGEL H M , SCHATTENKERK J K M EEFTINCK , MULDER J W , WESTEDT M L , VON DEM BORNE A E G KR 
Published: July 2010

SUMMARYAntibodies against cytoplasmic antigens of neutrophils, producing perinuclear (p-ANCA) as well as cytoplasmic staining with central accentuation (c-ANCA), have been described in non-HIV-infected patients with specific pathology such as glomerulonephritis and vasculitis. Here, we report on a patient with a vasculitis-like syndrome and a positive ANCA-test who appeared to he infected by HIV. Further analysis revealed that ANCA, p-ANCA as well as c-ANCA without central accentuation can be demonstrated in the serum of HIV+ individuals. In a cross-sectional study on individuals indifferent stages of HIV infection, we found that the occurrence of ANCA was limited to the symptomatic stages of HIV infection: p-ANCA was found in one out of 10 ARC patients and in two out of II AIDS patients with malignancies (AIDS-MAL), but not in AIDS patients with opportunistic infections (AIDS-OI). c-ANCA was found in four of the ARC patients, in two of the 14 AIOS-OI patients and in two AIOS-MAL patients. The presence of ANCA was not related to the degree of hypergammaglobulinaemia nor to specific symptomatology. ANCA containing sera from HIV+ individuals did not read with HEp2 cells nor with cytoplasmic antigens of lymphocytes, natural killer (NK) cells or eosinophils. Five out of the 11 (two p-ANCA and three c-ANCA) sera reacted weakly with cytoplasmic antigens of moncytes. All sera reacted with karyoplasts but not with cytoplasts prepared from neutrophils. These results suggest that HIV-ANCA might be directed against myeloid cell-specific granule constituents. However, sandwich-ELISAs with MoAbs against granule antigens that are frequently the target antigens of ANCA in HIV individuals were negative. Also immunoprcecipitation and immunoblotting, using lysates of neutrophil granules, did not allow further identification of the target antigens of HIV-ANCA.
Frequencies of HIV-reactive B cells in seropositive and seronegative individuals
Authors: ZUBLER R H , PERRIN L H , DOUCET A , ZHANG X , HUANG Y-P , MIESCHER P A 
Published: July 2010

SUMMARYPeripheral blood mononuclear cells (PBMC) from HIV-infected seropositive (HIV+) but not from normal, seronegative (HIV-) individuals are known to produce anti-HIV antibodies in vitro, in the absence or presence of pokeweed mitogen (PWM). Previous studies showed that up to 20–40% of spontaneously immunoglobulin-secreting B cells from HIV+ individuals are HIV-specific. To analyse the frequency of anti-HIV B cells among “total” peripheral blood B cells in the present study, we used a limiting dilution assay in which EL-4 thymoma cells induce clones of immunoglobulln-secreting cells in activated as well as resting B cells. Anti-HIV B cells were detected not only in 11/12 HIV+ individuals (with frequencies from 1/910 lo 1/21 500 B cells cultured; one negative test was from a person undergoing seroconversion), but also in 4/9 HIV normal blood donors (1/16200 to 1/49000 B cells cultured) and in 3/6 newborns from HIV mothers (1/11 800 to l/26 600 B cells cultured). The mean frequency was nine times higher in the HIV individuals than in the normal donors. As in previous studies, only the cells from HIV individuals generated anti-HIV antibodies in PBMC bulk cultures with or without PWM. The relative proportion of specific anti-HIV antibody total immunoglobulin in PBMC bulk cultures was 800 times higher by the mean than in EL-4 B cell cultures from HIV individuals (whereby the total immunoglobulin secretion for equal numbers of B cells cultured was 500 times lower for PBMC). These different results obtained with different assays suggest that in seropositives most anti-HIV B cells belong to an activated B compartment which is quite small, even in a disease with B cell hyperactivity. Therefore, the specific B cells are strongly diluted among the EL-4 cell-responsive, total B cells. On the other hand, the EL-4 assay can detect HIV-reactive B cells in the B ceil repertoire of normal, non-infected individuals.
LFA-1-dependent OKT3-driven T cell clusters in common variable immunodeficiency
Authors: RUDNICKA W , ENGLISH N , FARRANT J , NORTH M E , BRYANT A E , EDWARDS A J , STACKPOOLE A , WEBSTER A D B , BALFOUR B M 
Published: July 2010

SUMMARYThe triggering of the TCR/CD3 complex by anti-CD3 (OKT3) antibody leads to the formation of T cell clusters. In cultures of T lymphocytes from most normal individuals, the peak of cluster formation occurs at 24 h. but with cells from patients with common variable immunodeficiency (CVI) it was seen earlier al 4–9 h; in addition, the clusters were larger than normal, particularly at 9 h. Cluster formation by CVI and normal cells was dependent on temperature and divalent cations, but did not require Fc receptors. Since OKT3 clustering is known to be dependent on the LFA-l/ICAM-l adhesion system, the effect of monoclonal antibodies directed against these molecules was tested. A potent inhibitor was the antibody against the common beta chain of the integrin family (CD 18). But of four MoAbs against the alpha chains (CD 11), three inhibited and one stimulated T cell aggregate formation. Increased expression of LFA-I or ICAM-1 on CVI patients'T cells could not be demonstrated. The accelerated clustering was therefore probably due lo an increase in the proportion of cells carrying the activated form of LFA-1. The formation of large numbers of homotypic lymphocyte clusters might reduce the effective interaction between Band T cells, thus contributing to the depression of immunoglobulin synthesis observed in this disease.
IL-1-like production in adriamycin-induced nephrotic syndrome in the rat
Authors: BRICIO T , MOLINA A , EGIDO J , GONZALEZ E , MAMPASO F 
Published: July 2010

SUMMARYRats receiving a single dose of adriamycin (7·5 mg/kg) develop heavy proteinuria and morphological abnormalities similar to those observed in minimal change nephrotic syndrome in humans. IL-1-concomitance between enhanced I-a display by resident glomerular macrophages. IL-1-like cytokine secreted by whole isolated rat glomeruli and proteinuria was observed in adriamycin-injected rats during the experimental protocol. In addition, in vitro studies have shown that after stimulation with adriamycin or lipopolysaccharide (LPS) this cytokine is mainly produced by resident glomerular macrophages in culture. Although the precise mechanism of proteinuria in this model needs to be further studied, our results indicate that IL-1-like cytokine could be an important mediator implicated in the structural and functional disturbances occurring at the glomerular capillary wall level in adriamycin nephrosis.
An anti-peptide antibody that recognizes a neo-antigen in the CR1 stump remaining on erythrocytes after proteolysis
Authors: BARBOSA J E , HARRISON R A , BARKER P J , LACHMANN P J 
Published: July 2010

SUMMARYPrevious studies of erythrocyte CR1 levels in systemic lupus erythematosus (SLE) and other diseases with in vovo complement activation have led lo the conclusion that CR1 levels fall because of loss of CR1 from erythrocytes by proteolysis —predominantly in the liver. In order to measure the existence of proteolysed CR1 remnants on erythrocytes an antibody was raised to a peptide corresponding to the CR1 sequence between the proximal standard consensus repeat (SCR) and the transmembrane segment. This antipeptide antibody recognizes a neo-antigen found on trypsinized erythrocytes which has been demonstrated to represent the “CRI-stump”, The anti- ‘CR1-stump’ antiserum detects proteolysed CR1 on the ex vivo erythrocytes of a patient with cold haemolytic antibody disease (CHAD). However, higher affinity antibodies will be needed to make anti- CR1 -stump a satisfactory diagnostic reagent.
Inhibition of the reactive proliferation of lymphocytes by activated macrophages: the role of nitric oxide
Authors: DENHAM S , ROWLAND I J 
Published: July 2010

SUMMARYThe effects of nitric oxide synthesis by activated macrophages on concanavalin A (Con A) stimulated lymphocyte proliferation and the modulation of these events by extraneous l-arginine concentration were investigated. In 1 mM or 3 mM exogenous l-arginine, inhibition of proliferation of a fixed number of lymphocytes was progressively inhibited in the presence of increasing numbers of macrophages. This inhibition was related to increased nitric oxide synthesis by the macrophages and was suppressed in the presence or NG-monomethyl-l-arginine (NMMA), a specific inhibitor of nitric oxide synthesis. Inhibition of nitric oxide synthesis by 500 μM NMMA was less effective at high concentrations of macrophages, and in 5 mM as compared with 1 mM l-arginine. In the absence of exogenous L-arginine, NMMA inhibited lymphocyte proliferation in the presence of low numbers of macrophages but appeared to promote proliferation at high macrophage concentrations. Membrane separation of lymphocytes and macrophages led to loss of the nitric oxide mediated inhibitory effect on lymphocyte division except at the highest concentrations of macrophages used. Inhibition of lymphocyte proliferation could not be associated with l-arginine depiction of the media by macrophages or by the action of nitrite ions, a product of nitric oxide oxidation.
Soluble IL-2 receptor levels in patients with Graves'ophthalmopathy
Authors: PRUMMEL M F , WIERSINGA W M , VAN DER GAAG R , MOURITS M P , KOORNNEEF L 
Published: July 2010

SUMMARYIn various autoimmune diseases circulating levels of soluble 1L-2 receptor (sIL-2R) seem to be related to disease activity. Because reliable parameters of disease activity in Graves' ophthalmopathy are lacking, we measured sIL-2R levels in 47 patients with this disorder, The patients had Graves' disease, but no other immune-mediated diseases, had not yet received specific treatment for their ophthalmopathy and were euthyroid during the entire study period. Twenty-one of the 47 patients (45%) had sIL-2R values above the upper normal limit of 650 U/ml. as established in 20 healthy controls. There were no differences between patients with normal (median 469, range 280–644 U/ml) and elevated (median 946, range 678–1588 U/ml) sIL-2R levels regarding duration or severity of the eye disease (as assessed clinically from the total eye score). However, patients with severely enlarged eye muscles had higher sIL-2R values than patients with less severely enlarged eye muscles on CT scan. Patients with elevated sIL-2R tended to have a higher response rate (71%) to a 3-month course of prednisone, than those with normal levels (46%; P=0081). Since a successful outcome of prednisone treatment might be representative for disease activity, the elevated sIL, −2R levels seem to reflect active inflammation. Although the practical relevance of this finding in individual patients is limited, it underscores the importance of cell-mediated immune responses in this thyroid-related eye disease.
Limiting-dilution analysis of T cell reactivity to mycobacterial antigens in peripheral blood and synovium from rheumatoid arthritis patients
Authors: CRICK F D , GATENBY P A 
Published: July 2010

SUMMARYLimiting-dilution analysis (LDA) was used to quantify the frequency of Mycobacterium bovis BCG-and 65-kD-reactive T cells in paired samples of peripheral blood and synovial tissue from patients with rheumatoid arthritis, The frequency of BCG-reactive T cells detected in the peripheral blood of patients ranged from 1/585 to 1/7639 versus a control frequency range of 1/480 to 1/6773, The frequency of such cells in the synovium was found to be much lower than it was in peripheral blood; in fact, in 80% of patients synovial BCG-reactive T cells were not detected. The frequency of 65-kDreactive cells in the peripheral blood of each individual was lower than the frequency of BCG-reactive cells (range 1/3738 to 1/55 324), as would be expected. However, no synovial 65-kD-reactive cells were detected from any of the patients studied. The LDA assay for the 65-kD antigen was consistent with the single hit model, that for BCG was not. The relatively high proportion of mycobacterial-reactive precursors seen in the peripheral blood of non-vaccinated individuals may reflect a population of cells induced either by natural environmental exposure to mycobacteria or, given the highly conserved nature of heat shock proteins across phylogeny, by some other infection. The results also suggest that the frequent finding of reactivity to proteins such as the 65-kD heat shock protein contained within BCG may not be a generalized phenomenon in rheumatoid synovium.
Low-affinity antibodies against collagen type II produced by lymph node cells are associated with pathology in collagen-induced arthritis in rats
Authors: RAHMAN J , LOH J , STAINES N A 
Published: July 2010

SUMMARYThe relationship between the affinity of antibodies against type II collagen (CII) and arthritis was studied in rats immunized intradermally with bovine CII. Disease was associated with a higher mean titre of serum antibody and a lower mean functional antibody affinity (determined in a chaotropic dissociation assay) against both the immunizing bovine CII and homologous autoantigenic rat CII in comparison with the response in immunized rats that did not develop disease. The functional affinity of the antibodies present in the serum was found to correlate with that of antibodies produced in culture by cells from the lymph nodes draining the site of immunization with collagen. The reduction in mean functional affinity in the anti-collagen response may be the result of the increased production of antibodies of the lowest affinity and a consequent broadening of the affinity heterogeneity. It is proposed that production of low-affinity antibodies in the lymph nodes draining the site of immunization with collagen is important in the pathogenesis of collagen-induced arthritis in rats.