bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of an HLA-DR4-restricted T cell clone recognizing a protein moiety of small nuclear ribonucleoproteins (UsnRNP)
Authors: WOLFF-VORBECK G , HACKL W , FENNING S , KRAWINKEL U , LÜHRMANN R , PETER H H , SCHLESIER M 
Published: August 2010

SUMMARYIn sera of patients with mixed connective tissue disease(MCTD, Sharp Syndrome) high titres of IgG autoantibodies to UlsnRNP-specific proteins are found. The isolated occurrence of these autoantibodies is highly associated with the HLA-DR4 haplotype. snRNP-specific T cells are supposed to be involved in this autoantibody production. To address this question we cultured mononuelear cells from MCTD patients and healthy donors with a highly purified UsnRNP preparation from HeLa cells using bulk or limiting dilution cultures. Secondary responses to snRNP were detected only rarely with T cell lines from two patients and two controls, and turned out to be unstable during further expansion. One T cell line derived from a healthy individual retained its snRNP reactivity upon limiting dilution cloning and could be characterized in detail. The CD4+ T cell clone recognized native snRNP particles presented by monocytes in an HLA-DR4 (Bl*0401)-restricted manner. Separation of the protein and RNA moieties of snRNP particles revealed that the T cell clone responded specifically to the protein fraction, but not to RNA and diverse control antigens. Sequencing of the T cell receptor α and β chain cDNAs revealed that the clone used the Val4.2 and Vβ14 elements. Upon antigen-specific and mitogenic stimulation the T cell clone showed a ThI-specific cytokine pattern, and did not provide helper activity for in vitro immunoglobulin production. This study demonstrates the presence of self-reactive snRNP-specific T cells in a healthy donor. The T cell clone may not represent a helper T cell for the formation of UlsnRNP-specific autoantibodies.
Anti-5S RNA/protein (RNP) antibody levels correlate with disease activity in a patient with systemic lupus erythematosus (SLE) nephritis
Authors: GUIALIS A , PATRINOU-GEORGOULA M , TSIFETAKI N , AIDINIS V , SEKERIS C E , MOLITSOPOUIOS H M 
Published: August 2010

SUMMARYA patienl with systemic lupus erythematiosus (SLE) and nephritis without antibodies to dsDNA but with antibodies lo a 5S RNA/protcin (RNP) complex is presented. Combined RNA precipitation and Western blotting experiments strongly suggested that these newly Identified autoantibodics recognized a distinct epitope on the 1.5 ribosomal protein of the L5/5S RNP complex first described by steitz et al. [1]. Quantification of the anti-5S RNI* antibody levels was done by hybridizing Northern blots of immunoprecititated RNA from serial serum samples with a 32p-labelled oligoprobc specific for the 5S ribosomal RNA. These studies revealed a strong association between unti-5S RNP autoanlibody litre and severity of SLE nephritis over a 3-ycar prospective study. Our results indicate that the L5/5S RNP can be a target of autoimmune response, and may serve, in some cases, as marker of SLE severity and response to therapy.
Adhesion of peripheral blood lymphocytes of children with arthritis to human umbilical vein endothelial cells
Authors: OEN K , DANELL G , STEWART S , WILKINS J , TAZUMl K , JACOBSON K 
Published: August 2010

SUMMARYTo determine whether adhesion of peripheral blood lymphocytes (PBL) of patients with juvenile rheumatoid arthritis (JRA) may be enhanced, adhesion of PBL of children with JRA. children with seronegative spondyloarthropathies (SSA). age-appropriate and adult controls, to human umbilical vein endothelial cells (HUVEC) was assessed in vitro. B and CD4 T lymphocytes in initial, adherent, and non-adherent cell fractions were identified by flow cytometry. B lymphocytes of all the younger subjects combined had a higher adherence to activated HUVEC compared with B lymphocytes of the adult donors. Except for greater adherence of HLA-DR+ CD4 T cells, lymphocytes of children with JRA showed no enhanced adhesion to either unactivated or activated HUVEC. The percentage of B cells adherent to activated HUVEC in each of the subject groups was 1-5 3-6-fold higher than adherent CD4 T lymphocytes. Surface analyses indicated higher percentages of CD49d (α4)+ and CD29 (β1)+ CD4 T lymphocytes in adherent cells, but less of a differential in CD49 (α4)+ and no difterence in CD29(βl)+ B lymphocytes. There were fewer Leu-8(L-selectin)+ B and Leu-8+ CD4T cells among adherent cells. The data suggest a greater adhesive capacity of B lymphocytes compared with CD4 T lymphocytes which is unrelated to disease, and the possibility that B lymphocytes may utilize adhesion molecules distinct from those of CD4 T lymphocytes. Only a small subset of T cells of patients with JRA may have an enhanced capacity for adhesion to endothelium.
High-density proteoglycan induces specific suppression of adjuvant-induced arthritis in rats
Authors: SAIKAWA I , HOTOKEBUCHI T , MIYAHARA H , TOKITO T , MAEDA T , ARITA C , SUGIOKA Y 
Published: August 2010

SUMMARYIn vitro data support the view that T cells in adjuvant-induced arthritis (AIA) respond to the proteoglycan (PG) component of articular cartilage; however, an in vivo role for PG in AIA has yet to be shown. To do so. we examined the effects of pretreatment with bovine cartilage high density PG (HDPG) on AIA induced by heat-killed Mycobacterium butyricum in Lewis rats. Purified bovine cartilage HDPG emulsified in Freund's incomplete adjuvant (FIA) was injected intradermally into rats 7 days before challenge with Myco. butyricum. The severity of arthritis was significantly suppressed in rats pretreated with as little as 0·75 mg of HDPG, and the arthritis was completely suppressed in rats pretreated with 3·0 mg of HDPG. This suppression was specific, as the same treatment did not protect against type II collagen-induced arthritis. Suppression of AIA is primarily a property of the HDPG, as suppression of the arthritis was significantly less with pretreatment with 3.0 mg of middle density fractions of PG, and no suppression was observed with pretreatment with the lowest density fraction of PG. Thus we report that pretreatment with cartilage HDPG, but not lower density PG, can induce specific suppression of AIA. These in vivo results support the view that immunity to cartilage HDPG plays a major role in the pathogenesis of AIA, and can induce specific tolerance to this type of arthritis.
Abnormalities in subset distribution, activation, and differentiation of T ceils isolated from large intestine biopsies in HIV infection
Authors:   THE BERLIN DIARRHOEA/WASTING SYNDROME STUDY GROUP, SCHNEIDER T , ULLRICH R , BERGS C , SCHMIDT W , RIECKEN E O , ZEITZ M 
Published: August 2010

SUMMARYIntestinal T cells have a unique stale of activation and differentiation which might specifically affect or be affected by HIV infection. Lymphocyte subsets in the peripheral blood are well characterized., but our knowledge about intestinal lymphocytes in HIV infection is incomplete. We therefore analysed lymphocytes isolated from large intestine biopsies of AIDS patients and controls by threecolour cytofluorometry. In the large intestine of HIV-infected patients CD4 T cells were reduced and CD8 T cells were increased compared with controls. Most of the CD8 T cells in the colorectal mucosa of AIDS patients were of the cytotoxie phenotype. Activated and resting CD4T cells were similarly reduced, the expression of CD25 and HLA-DR of CD8 T cells was unaltered and increased. respectively. In intestinal CD4 T cells the expression of CD29 was decreased, but the expression of CD45RO and HML-1 was normal. CD8 T cells had a decreased expression of all these differentiation markers. Our findings demonstrate substantial alterations in subset distribution, activation, and differentiation of large intestine T cells, which may contribute to the secondary infections and malignancies commonly observed in the gut of AIDS patients.
Serial functional affinity of autoantibodies in anti-glomerular basement membrane disease
Authors: MARRIOTT J B , OLIVEIRA D B G 
Published: August 2010

SUMMARY
Anti-glomertilar basement membrane (GBM) disease is caused by an autoantibody directed against an epilope on ihc α3 chain of type IV cullagen. Animal models demonstrate that the higher the affinity of such antibodies, the greater the degree of glomerular injury. Affinity maturation (the process whereby somatic mutation followed by antigen selection leads to an increase in affinity of antibody) might therefore be of pathogenic significance if it occurs in human anti-GBM disease. We have examined serial samples from nine patients with anti-GBM disciisc and looked for evidence of changing functional affinity by measuring the inhibition of binding produced by the mild chaotrope diethylamine (DEA) in an anti-GBM antibody ELISA. Seven patients showed no change in the inhibition produced by DEA with time. Two patients showed an apparent decrease with time in the inhibition produced by DEA; this apparent increase in functional affinity proved, on further investigation, to represent simply ihe loss of anti-GBM antibodies. These results may imply that affinity maturation has been completed by the time that patients present wiih anti-GBM disease. If there had been evidence for a further increase in functional affinity after this point then this might have added extra urgency to the need for removal of these autoantibodies as part of treatment.
Increased cyclosporine sensitivity of T cells from cord blood compared with those from the adult
Authors: MCDOUALL R M , SUITTERS A J , SMITH H , YACOUB M H , ROSE M L 
Published: August 2010

SUMMARYDespite the increasing numbers of paediatric transplants performed, little is knowtn about the immuine responses of T lymphocytes in human neonates. Here we have compared the effects of cyclosporinc on the phytohacmagglutinin (PHA) response of immature (cord) and mature (adult) lymphocytes using the following parameters of activation: (i) proliferation, measured by ‘H-thymidine uptake: (ii) expression of cell surface IL-2 receptor; (iii) release of IL-2 into the supernatant. Cyclosporine was added to cultures of PHA-stimulated lymphocytes at doses ranging from 5 to 5000 ng/ml. The proliferative response of cord lymphocytes was considerably more sensitive to cyclosporine at each dose, so that 50% inhibition was achieved by 6 ng/ml and 21·5 ng/ml doses of cyclosporine on cord and adult lymphocytes, respectively, Expression of the IL-2 receptor by PHA-activated T cells and their subsets was assessed by flow cytometry. Cyclosporine inhibited IL-2 receptor expression to a significantly greater degree in cord CD4 and CD8 cells (49·7% and 70·1%) than in adults (17·9% and 30·0%). Biologically active IL-2 release was measured using the IL-2-dependent cell line CTLL-2. Cyclosporine at doses 50–5000 ng/ml produced 80–99% inhibition of both cord and adult responses. However, at very low doses (5 ng/ml) cyclosporine produced 69·3%, inhibition of cord lymphocytes, compared with 42·0% of adult lymphocytes. These results suggest that the T cells of neonates are considerably more sensitive to cyclosporine than are adult T cells.
Mucosal tolerance and suppression of collagen-induced arthritis (CIA) induced by nasal inhalation of synthetic peptide 184-198 of bovine type II collagen (CII) expressing a dominant T cell epitope
Authors: Staines N A , Harper N , Ward F J , Malmström V , Holmdahl R , Bansal S 
Published: August 2010

SUMMARYThe purpose of the study was to map the dominant T cell epitope of the CB11 sequence of CII in RT1u haplotype rats and to determine if, when used as a synthetic peptide, it would induce tolerance to protect against CIA. A dominant epitope corresponding to residues 184–198 included in the sequence of the CB11 fragment of bovine CII was identified in proliferation assay using peptides in an epitope scanning system using synthetic peptides of 15 amino acids, overlapping by 12 amino acids. This epitope is bovine-specific, but cross-reacts with the corresponding rat peptide. Minor epitopes in the bovine CB11 sequence were also autoantigenic. Use of independently synthesized and purified 184–198 peptide confirmed its dominance in the T cell responses of arthritic rats. The peptide itself was not arthritogenic. Cells from lymph nodes draining arthritic feet were particularly responsive to the dominant peptide sequence, and showed evidence of epitope spreading to include reactions to at least four subdominant epitopes. Mucosal tolerance was successfully induced by instilling CII into the nose of rats before induction of CIA; this was found to delay the onset of disease, reduce mean disease severity, shift the anti-CII antibody response to favour antibodies of the IgGl, rather than the IgG2b isiotype, and to reduce T cell reactivity to both CII and to the 184–198 peptide. The dominant 184–198 peptide itself had the same tolerogenic effects when given nasally to rats daily, on the 4 days immediately preceding the induction of CIA. Two forms of CIA with acute and delayed disease onset were each modified by pre-treatment with the peptide. This study demonstrates that mucosal tolerance to CII can be induced by delivering it nasally in a way similar to that achieved previously by oral delivery, and that the use of an immunodominant epitope contained in a synthetic peptide will also suppress the immunologic and arthritic responses to collagen.
Azurocidin is a novel antigen for anti-neutrophil cytoplasmic autoantibodies (ANCA) in systemic vasculitis
Authors: Zhao M H , Lockwood C M 
Published: August 2010

SUMMARYWe isolated a 27-kD protein using cation exchange chromatography from an acid extract of neutrophil granules. N-terminal amino acid sequence analysis of the first 10 residues showed that this protein is azurocidin, a member of the family of neutral serine proteinase found in the neutrophil, which shares amino acid sequence homology with the three other neutral serine proteinases, elastase, proteinase 3 (PR3) and cathepsin G, but unlike them is without proteolytic activity. To test whether, in addition to these proteases, azurocidin might be a target for the humoral autoimmune responses associated with human vasculitis, 185 indirect immunofluorescence (IIF)-positive ANCA sera, made up of four groups of sera with specificities for PR3 (n= 37), myeloperoxidase (MPO; n= 50), bactericidal/permeability-increasing protein (BPI; n= 41) and sera that recognized none of them (triple negative, n= 57), and 46 normal sera were screened for IgG anti-azurocidin antibodies using an ELISA incorporating purified azurocidin. Twenty of the 185 IIF-positive sera and 2/46 normal sera displayed reactivity with azurocidin. Positive sera could blot the 27-kD band by Western blot analysis. Further study of the 20 positive sera revealed that: (i) 10 also had autoreactivity for MPO, of which six additionally recognized lactoferrin; (ii) two had reactivity with BPI; (iii) the remaining eight sera were positive only for azurocidin. All 20 sera were from patients with systemic vasculitis, and four of the six sera with triple reactivity (for azurocidin, MPO and lactoferrin) were from patients with hydralazine-induced vasculitis. We concluded that: (i) azurocidin is a novel ANCA antigen; (ii) anti-azurocidin antibodies from a subgroup of patients might represent the consequence of a drug-induced multi-clone activation.
Detection of hepatitis C virus (HCV) proteins by immunofluorescence and HCV RNA genomic sequences by non-isotopicin situhybridization in bone marrow and peripheral blood mononuclear cells of chronically HCV-infected patients
Authors: Sansonno D , Iacobelli A R , Cornacchiulo V , Iodice G , Dammacco F 
Published: August 2010

SUMMARYImmunofluorescence (IF) to detect HCV antigens and non-isotopic in situ hybridization (NISH) to detect HCV RNA genome were carried out on bone marrow (BM) and peripheral blood (PB) mononuclear cells (MC) of 11 chronically HCV-infected patients. In four patients (36.4%) HCV antigens were detected in monocytes macrophages as well as in B lymphocytes in both BMMC and PBMC. Positive T lymphocytes in BMMC were found in three of them, but only one patient showed positive T cells in PBMC. NISH invariably demonstrated minus and plus HCV RNA genomic strands either in monocytes macrophages or B and T lymphocytes in BMMC and PBMC in the four HCV antigen-positive patients and in two further patients not expressing viral proteins in blood MC. IF signals appeared diffusely distributed within the cytoplasm, or as brilliant granules in distinct submembrane areas or else in cytoplasm membrane. Nuclei never stained. Similarly, NISH displayed HCV RNA accumulation restricted to MC cytoplasm only, nuclei being persistently negative. NISH, however, was unable to detect cell membrane signal. Infection of blood MC is a common event in naturally acquired HCV infection, since none of these patients was conditioned by immunomodulating or immunosuppressive therapies. No difference was found in terms of mean age, length of disease, anti-HCV immune response, type and severity of chronic liver damage between patients with HCV-infected MC and patients without cell infection. These results demonstrate that HCV can infect BMMC and PBMC that represent important extrahepatic sites of virus replication, and may help to explain the immunological abnormalities observed in chronic HCV carriers.
Selected Th1 and Th2 cytokine mRNA expression by CD4+ T cells isolated from inflamed human gingival tissues
Authors: Fujihashi K , Yamamoto M , Hiroi T , Bamberg T V , McGhee J R , Kiyono H 
Published: August 2010

SUMMARYElevated numbers of plasma cells are associated with localized and chronically inflamed gingiva of patients with adult periodontitis. However, only limited information is currently available as to how cytokines produced by CD4+ T cells are involved in these increased B cell responses in affected gingival tissues. When gingival mononuclear cells (GMC) were isolated from inflamed tissues and examined by flow cytometry, ∼20–30% of lymphocytes were CD4+ T cells. For the analysis of Th1 and Th2 cytokine expression by these CD4+ T cells, RNA was extracted and reverse transcriptase-polymerase chain reaction (RT-PCR) was performed by using specific 5' and 3' primers for interferon-gamma (IFN-γ) and IL-2 (Th1), IL-4, IL-5, IL-6, IL-10 and IL-13 (Th2) and β-actin (internal control). Two distinct cytokine profiles were noted based on the expression of selected Th1 and Th2 cytokines, where one pattern was represented by expression of mRNA for IFN-γ, IL-6, IL-10 and IL-13, while the second consisted of mRNA for IFN-γ, IL-6 and IL-13. In most samples, mRNA for IL-2, IL-4 and IL-5 were not detected by cytokine-specific RT-PCR. When RNA was isolated from CD4+ T cells of concanavalin A-stimulated peripheral blood mononuclear celts (PBMC) of the same patients and examined by RT-PCR. mRNA for all Th1 and Th2 cytokines were detected. These findings suggest that although human CD4+ T cells are capable of producing an array of Th1- and Th2-type cytokines, the CD4+ T cells associated with periodontitis are limited to production of IFN-γ, IL-6, IL-13 and in some instances IL-10. CD4+ T cells from diseased periodontal tissues are divisible into two groups based upon whether or not IL-10 is produced, together with IFN-γ, IL-6 and IL-13.
A prognostic role for anti-phosphatidyl choline antibodies in human cerebral malaria
Authors: Das B K , Parida S , Ravindran B 
Published: August 2010

SUMMARY
Anti-phosphatidyl choline antibodies (αPC) have been measured in adult patients from Orissa, India with Plasmodium falciparum infection of varying clinical severity. Significantly raised levels of αPC were observed in infected individuals in comparison with controls. The IgG αPC were found to be generally more than IgM αPC in most cases. The IgG αPC levels were significantly more in those cases of cerebral malaria who recovered fully after quinine administration in comparison with fatal cases not responding to quinine therapy, indicating a role for αPC in prognosis of adult cerebral malaria. There was no significant difference in levels of αPC IgG between non-cerebral and fatal cerebral malaria patients, indicating an absence of a direct protective role in the development of cerebral manifestations. Subgroup typing of IgG with αPC activity indicated IgG3 to be the predominant type, followed by IgG2. IgG1 and IgG4. A significant inverse relationship between serum tumour necrosis factor-alpha (TNF-α) levels and IgG1 antibodies with αPC activity was found, emphasizing the importance of αPC in modifying disease severity. These observations appear to give credence to recent reports in the literature indicating that toxic malarial antigens consist of phospholipids and that antibodies to phospholipids (αPL) inhibit such antigens in experimental systems.
Aggravation of experimental allergic encephalomyelitis (EAE) by administration of nitric oxide (NO) synthase inhibitors
Authors: Ruuls S R , van der Linden S , Sontrop K , Huitinga I , Dijkstra C D 
Published: August 2010

SUMMARYMacrophages constitute a large proportion of the inflammatory cells that infiltrate the central nervous system (CNS) of animals with EAE. Through the production of inflammatory mediators these infiltrating macrophages can contribute to the regulation of the immune reaction within the CNS, that eventually results in neurological deficits associated with EAE. NO, a free radical produced by macrophages and other cell types, has been put forward as such an immune mediator. In the present study we show that macrophages isolated from the CNS of Lewis rats with clinical signs of EAE produce elevated amounts of NO. We treated rats, in which EAE was induced, with Nw-nitro-L-arginine-methylester or NG-monomethyl-L-arginine, inhibitors of NO synthase, either systemically via intraperitoneal injection, or intracerebrally via a cannula placed in the lateral ventricle. Both treatments resulted in a marked aggravation of clinical signs of EAE. These data point to an important role of NO, produced by infiltrating macrophages, as an immune-suppressor in the disease process during EAE.
Production of IL-6 by T cells from the femoral head of patients with rapidly destructive coxopathy (RDC)
Authors: Tamai M , Sagawa K , Kawabata R , Inoue A , Itoh K 
Published: August 2010

SUMMARYRDC is a syndrome with unknown etiology that causes rapid destruction of a hip joint. We have investigated the production of osteoclast-activating cytokines (IL-6, IL-1α and tumour necrosis factor-alpha (TNF-α)), interferon-gamma (IFN-γ) and IL-8 by T cells in the affected joint. The level of IL-6 produced by the T cell lines (TCL) established from the femoral head was significantly higher than that from patients' or healthy donors' peripheral blood mononuclear cells (PBMC). IL-6 production by the TCL from synovial membrane or from patients' PBMC was also significantly higher than that from healthy donors' PBMC. IL-1α production by the TCL from the femoral head was significantly higher than any of the other groups when all the TCL were used for the analysis. TNF-α production was highest in the TCL from patients' PBMC. The levels of IFN-γ or IL-8 were not significantly different among these four groups. The plasma levels of all these cytokines except for IFN-γ, that was rather lower, in RDC patients were not significantly different from those in osteoarthrosis or trauma patients, or healthy donors. These results suggest that T cells at the affected femoral head, and also synovial membrane to some extent, are involved in bone resorption through the production of IL-6 and probably IL-1α in patients with RDC.