bluuebunny/crossref_metadata_2025_split huggingface dataset:
Memory lymphocytes from tuberculous effusions: purified protein derivative (PPD) stimulates accelerated activation marker expression and cell cycle progression
Authors: Lukey P T , Latouf S E , Ress S R 
Published: November 2003

SUMMARY
Accelerated PPD-specific proliferation and generation of CD4+ cytotoxic effectors by mononuclear leucocytes (MNL) from tuberculous effusions (EMNL) has been previously reported by our laboratory. In order to explore the contribution of the state of activation of MNL to accelerated reactivity, EMNL and peripheral blood (PB)MNL from seven patients with tuberculosis were assessed both ex vivo and after PPD stimulation. Flow cytometry revealed no difference in the activation state (IL-2 receptor and HLA-DR expression) or cell cycle progression ex vivo. However, CD4+CD29+ memory T cells were accumulated in EMNL compared with PBMNL. In vitro stimulation of EMNL with PPD resulted in accelerated expression of activation markers and progression through the cell cycle (peak after 4 days), whilst PBMNL exhibited normal activation kinetics (peak after 7 days). Accelerated reactivity could not be accounted for by quantitative differences in effusion CD4+CD29+ memory T cells compared with blood, but may be due to a qualitative difference in effusion memory T cells, which are shown to be in a post-activation state of differentiation. T cells entering S and G2/M phases of the cell cycle were largely of the activated memory phenotype. Activation marker expression occurred in association with up-regulation of CD4 antigen expression on the surface of EMNL. Thus accelerated expression of activation markers and cell cycle progression by CD4+CD29+ memory T cells may in part account for accelerated PPD reactivity in tuberculous effusions.
Antibodies to interferon (IFN) in hepatitis C patients relapsing while continuing recombinant IFN-α2 therapy
Authors: Antonelli G , Giannelli G , Currenti M , Simeoni E , del Vecchio S , Maggi F , Pistello M , Roffi L , Pastore G , Chemello L , Dianzani F 
Published: November 2003

SUMMARY
A number of trials have demonstrated that IFN-α is effective in chronic hepatitis C virus infection. It is known, however, that a number of chronic hepatitis C patients experience, after an initial response to IFN, disease reactivation or relapse (also called ‘breakthrough’) while IFN therapy is still ongoing. Since in a number of clinical conditions a significant correlation between development of antibodies to IFN and failure of therapy has been established, we addressed the possibility that the development of antibodies to IFN may take part in the relapse occurring in hepatitis C patients during recombinant IFN-α (rIFN-α) therapy. The prevalence of neutralizing (NA) and binding antibodies (BA) to rIFN-α2 has been evaluated in 45 patients with chronic hepatitis C treated with rIFN-α2a who first normalized aminotransferase (ALT) levels, and subsequently showed disease reactivation while on treatment. The presence of NA and BA was tested before therapy, during the response to IFN treatment, and at the time when ALT started to rise again to abnormal levels. The results showed that no patients had detectable antibodies to IFN before therapy and during the period of response to the therapy, while most of them (88.9%) developed NA and/or BA to IFN-α2 concomitantly with disease reactivation. In particular, in 29 of the 45 patients (64.4%) ALT normalized on treatment and rose to abnormal levels when NA appeared in their serum, while in 11 of the 16 (68.8%) remaining patients the relapse was associated with BA development. The frequency of seroconversion in these patients is significantly higher than that observed in the control group. These data indicate that antibodies to IFN may be responsible for breakthrough in the majority of patients showing disease reactivation while rIFN-α therapy is still ongoing.
Inhibitory effect of clarithromycin on costimulatory molecule expression and cytokine production by synovial fibroblast-like cells
Authors: Matsuoka N , Eguchi K , Kawakami A , Tsuboi M , Kawabe Y , Aoyagi T , Nagataki S 
Published: November 2003

SUMMARY
This study was undertaken to investigate the immunomodulatory effect of clarithromycin against synovial fibroblast-like cells (synoviocytes). Synovial tissue obtained from rheumatoid arthritis (RA) or osteoarthritis (OA) patients was enzymatically digested to separate synoviocytes. The synoviocytes were cultured with or without cytokines in the presence of various concentrations of clarithromycin. The expression of costimulatory molecules was examined on the surface of the synoviocytes, using specific MoAbs and flow cytometry. The production of cytokines by synoviocytes was also measured using an immunoenzymatic assay. Finally, autologous T cells were stimulated by interferon-gamma (IFN-γ)-treated synoviocytes in response to purified protein derivative (PPD). In some experiments, MoAbs specific for costimulatory molecules or clarithromycin were added and 3H-thymidine incorporation was counted. Intercellular adhesion molecule-1 (ICAM-1), LFA-3 and vascular cell adhesion molecule-1 (VCAM-1) were detected on the surface of both RA and OA synoviocytes. However, ICAM-2, B7–1 and B7–2 were not detected, and cytokines failed to induce these molecules. Both spontaneous and up-regulated expression of ICAM-1, LFA-3 and VCAM-1 by IFN-γ, IL-1β or 12-o-tetradecanoyl phorbol 13-acetate (TPA) were markedly suppressed by clarithromycin in a dose-dependent manner at concentrations between 0.1 and 10 μg/ml. The production of IL-1β, IL-6, IL-8, granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) but not IL-1α and tumour necrosis factor-alpha (TNF-α) by synoviocytes was detected. Clarithromycin significantly suppressed the production of these cytokines, but did not enhance IL-10 production. Finally, autologous T cells were stimulated by IFN-γ-treated synoviocytes in response to PPD. As clarithromycin suppressed HLA-DR and costimulatory molecule expression was enhanced by IFN-γ, autologous T cell proliferation was markedly inhibited by clarithromycin. Clarithromycin has a considerable immunosuppressive effect on synoviocytes by inhibiting costimulatory molecule expression, cytokine production and antigen-specific T cell proliferation induced by synoviocytes.
Definition of three minimal T helper cell epitopes of rubella virus E1 glycoprotein
Authors: Marttila J , Ilonen J , Lehtinen M , Parkkonen P , Salmi A 
Published: November 2003

SUMMARY
To characterize T cell-recognized epitopes on rubella virus (RV) E1 glycoprotein, IL-2-dependent RV-specific T cell lines were established from 14 rubella-seropositive healthy donors. The responses of these lines were studied by using a panel of 94 partially overlapping synthetic peptides of 15 amino acids (aa) length covering the known nucleotide sequence of RVE1 glycoprotein. Two to seven peptide-defined epitopes were recognized by the T cell lines, but a large interindividual variation was found. T cell reactivity was most often localized to the regions between aa 276 and 290, aa 381 and 395 and aa 410 and 420. Analysis of overlapping, truncated peptides revealed three minimal T helper cell epitopes VIGSQARK, KFVTAALLN and RVIDPAAQ in aa positions 280–287, 385–393 and 412–419, respectively.
Human monoclonal rheumatoid factors augment arthritis in mice by the activation of T cells
Authors: Ezaki I , Okada M , Yoshikawa Y , Fujikawa Y , Hashimoto M , Otsuka M , Nomura T , Yamamoto K , Watanabe T , Shingu M , Nobunaga M 
Published: November 2003

SUMMARY
In order to investigate the in vivo role of rheumatoid factor (RF), the effects of the administration of human monoclonal (m) IgM-RF and IgG-RF on the development of arthritis in mice were examined. The administration of human mRFs into mice immunized with type II collagen (CII) markedly enhanced the clinical score and paw swelling. The severity of arthritic joint disease with a marked infiltration of lymphoid cells, proliferation of synovial membrane, pannus formation and destruction of articular cartilage was significantly enhanced in both groups receiving RF (RF-enhanced arthritis). Skin ulcers were also observed in some of these RF-enhanced arthritis mice, whereas no such signs were observed in CII-immunized mice without mRFs. Both IgM-RF and IgG-RF increased CII-specific IgG antibodies in circulation, and the severity of arthritis correlated with the production of high titres of anti-CII antibodies. In vivo treatment of RF-enhanced arthritis mice with an anti-CD4 MoAb or an anti-CD8 MoAb inhibited the induction and progression of arthritis in these mice. Administration of RF to severe combined immunodeficient (SCID) mice with arthritis developed by the transfer of spleen cells from CII-immunized mice, prolonged the arthritis and enhanced the severity. This murine model of RF-enhanced arthritis may provide a useful tool for analysing the pathogenesis of rheumatoid arthritis in RF-positive patients.
Antibody cross-reactivity induced by the homologous regions in glutamic acid decarboxylase (GAD65) and 2C protein of coxsackievirus B4
Authors: Lönnrot M , Hyöty H , Knip M , Roivainen M , Kulmala P , Leinikki P , Åkerblom H K ,   Childhood Diabetes in Finland Study Group
Published: November 2003

SUMMARY
GAD65 contains an amino acid sequence which is highly homologous with a sequence in the 2C protein of coxsackievirus B4 (CBV4-2C). In the present study the possibility that this region could contain an epitope capable of inducing immunological cross-reactivity between CBV4-2C and GAD65 was evaluated. Six out of seven rabbit sera, which were raised against seven different synthetic peptides carrying various modifications of the homology sequence, showed cross-reactivity between 2C, GAD65 and GAD67 derived peptides in ELISA. There was substantial cross-reactivity between 2C and GAD65 peptides, but not between 2C and GAD67 peptides. The most cross-reactive peptides were those corresponding to the 2C sequences FIEWLKVKILPEVKEK and KILPEVKEKHEFLSRL. When the binding of the four 2C peptide-specific sera to the GAD65 protein was analysed in immunoprecipitation, two sera were found to be cross-reactive (anti-FIEWLKVKILPEVKEK and anti-WLKVKILPEVKEKHEF). One of these (anti-WLKVKILPEVKEKHEF) reacted also with coxsackie B virus (CBV)-infected cells. Antibodies against this epitope were induced during enterovirus (including CBV) infections in initially healthy children who later progressed to clinical insulin-dependent diabetes mellitus (IDDM). Antibody responses were frequent also in constantly GAD65 antibody-negative non-diabetic children, and antibody levels did not differ between newly diagnosed IDDM patients and matched control subjects. Blocking experiments confirmed that the observed reactivity of both rabbit and human antibodies was immunologically specific. The results suggest that the epitope is antigenically highly similar in 2C and GAD65, and that peptide immunization induces antibodies which cross-react with these molecules. However, the significance of this phenomenon in the pathogenesis of IDDM remains to be confirmed, as the peptide antibody levels were similar in patients with recent-onset IDDM and in control subjects.
Role of IL-4 in delayed type hypersensitivity
Authors: Asherson G L , Dieli F , Sireci G , Salerno A 
Published: November 2003

SUMMARY
IL-4 plays a key role in the contact sensitivity skin reaction. This has several implications. First, the view that contact sensitivity (CS) is only mediated by cells with a Th1 profile of cytokine secretion needs modification, in the light of the essential role of IL-4 at the effector stage. Second, the concept of a single cell involved in the systemic transfer of CS is no longer tenable, as it is known that both αβ and γδ cells are required. Studies with the cell lines (which contain both αβ and a few γδ cells) suggest that this double requirement may involve the action of IL-4 on γδ cells, which bear receptors for IL-4. Finally, the view that T cell lines only transfer CS when injected locally, but not when injected intravenously (systemic transfer), is correct but incomplete, as T cell lines actually give systemic transfer of CS, providing the cell line or the recipient is treated with IL-4.
Increased mucosal synthesis of rheumatoid factor (RF) in coeliac disease
Authors: Hällgren J , Knutson F , Lavö B , Hällgren R 
Published: November 2003

SUMMARY
Increased serum levels of RF have been reported in patients with gluten sensitivity. The objective of this study was to investigate the in vivo secretion of different isotypes of RF in the small bowel in coeliac disease. Nineteen patients were investigated by perfusion of a defined jejunal segment, and the jejunal perfusion fluid was analysed for the presence of IgA and IgM anti-Fc (IgG). Five of the patients studied had serum IgA deficiency. Patients with partial/subtotal villous atrophy but no IgA deficiency (n = 7) had a four-fold increase of IgM-RF (P&lt;0.001) and a three-fold increase of IgA-RF (P&lt;0.001) compared with healthy controls (n = 29). Patients with normal jejunal mucosa but no IgA deficiency (n = 7) had similar IgA-RF and IgM-RF concentrations to healthy controls. Patients with serum IgA deficiency had no IgA-RF detectable in jejunal fluid but the highest IgM-RF concentrations, in particular in active disease. The coeliac patients had serum levels of IgA-RF and IgM-RF within the reference ranges. Jejunal fluid levels of IgA-RF and IgA-anti-gliadin antibodies were significantly correlated (P&lt;0.001). The data indicate that enhanced jejunal mucosal production of RF occurs above all in active coeliac disease. The findings suggest that the immune response to gluten induces a mucosal RF synthesis.
Inverted Vδ1/Vδ2 ratio within the T cell receptor (TCR)-γδ T cell population in peripheral blood of heart transplant recipients
Authors: Vaessen L M B , Schipper F , Knoop C , Claas F H J , Weimar W 
Published: November 2003

SUMMARY
We investigated the levels of TCR-γδ T cells and their subpopulations Vδ1 and Vδ2 in the peripheral blood lymphocytes (PBL) of 28 heart transplant (HTx) patients. Patients (n = 10) receiving cyclosporin A (CsA) for treatment of a nephrotic syndrome (NS) and 10 healthy individuals served as controls. There was no difference in levels of TCR-γδ T cells between the different groups. However, an elevated proportion of Vδ1+γδ T cells was found in the PBL of HTx patients, especially when these cells were present in their graft-infiltrating lymphocyte (GIL) cultures. Vδ1+γδ T cells of HTx patients showed normal expression of CD45RO and lacked the activation markers CD25 and HLA-DR. After expanding in IL-2-containing medium, PBL cultures of HTx patients more often were dominated by Vδ1 cells than PBL cultures of controls, in which Vδ2 cells were predominantly grown. The aberrant composition of the TCR-γδ population in HTx patients was not a result of immunosuppressive medication, since the proportion Vδ1+γδ T cells was normal in the PBL of the NS patients receiving a similar dose of CsA. It is postulated that long-term antigenic stimulation by the graft, at low level, might be responsible for the altered composition of the γδ pool in the HTx patients. Since no donor HLA-specific γδ T cells have been detected, other ligands, such as heat shock proteins, may be involved.
Prevalence of hepatitis C in patients with primary antibody deficiency
Authors: Webster A D B , Brown D , Franz A , Dusheiko G 
Published: November 2003

SUMMARY
Concern over sporadic hepatitis C virus (HCV) infection from treatment with contaminated immunoglobulin in patients with immunodeficiency prompted us to screen serum from 44 patients for HCV RNA. We found no evidence of either horizontal or iatrogenic infection in our Clinic, except in two patients known to have received contaminated batches, and in one who had had regular plasma infusions. Thus, common variable immunodeficiency (CVID) patients in England do not have a high incidence of HCV infection despite exposure to various immunoglobulin products. This contrasts with the recently reported high prevalence in similar patients in Italy. Although our data reinforce the impression that both intramuscular and current licensed i.v. preparations in the UK are safe, manufacturers should be encouraged to PCR screen all batches of immunoglobulin for HCV.
Normal levels of soluble E-selectin, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) decrease with age
Authors: Nash M C , Wade A M , Shah V , Dillon M J 
Published: November 2003

SUMMARY
sE-selectin, sICAM-1, sVCAM-1 and von Willebrand factor (vWF) were assayed in 238 samples in a longitudinal study of 81 normal children from 9.5 to 15.5 years old. Multilevel modelling was used to quantify changes with age. sE-selectin, sICAM-1 and sVCAM-1 all fell significantly over the age range (by 17%, 16%, and 10%, respectively). In contrast, levels of vWF were not age-dependent. Our findings highlight the need for age-matched controls when studying cell surface adhesion molecules in disease groups, and may imply developmental changes in expression of these molecules and their shedding from the cell surface.
Hepatitis B virus (HBV)-specific in vitro antibody production by peripheral blood mononuclear cells (PBMC) after vaccination by recombinant hepatitis B surface antigen (rHBsAg)
Authors: Ducos J , Bianchi-Mondain A-M , Pageaux G , Conge A M , Poncet R , Vendrell J P , Segondy M , Serre A 
Published: November 2003

SUMMARY
To study the immunization induced by rHBsAg, we analysed the in vitro antibody production (IVAP) to HBsAg by PBMC from 18 subjects vaccinated by two injections on days 0 and 30. HBsAg-specific IVAP was detectable in all subjects after both the first and the second injection, and lasted for about 10 days and then disappeared. However, when the spontaneous HBsAg-specific IVAP became negative, HBsAg stimulation of PBMC cultures induced again a specific HBsAg IVAP. Cultures of cell populations separated by erythrocyte rosetting or Percoll density centrifugation showed that the cells responsible for spontaneous secretion, after in vivo stimulation, were low-density B lymphocytes. High-density B lymphocytes were involved in anti-HBs production induced by in vitro stimulation when spontaneous secretion disappeared. These data suggest that the IVAP test could be a source of important information along with serologic analysis for exploration of the immune response to hepatitis B vaccine.
Experimental T cell-mediated inflammatory reactions in the murine oral mucosa. II. Immunohistochemical characterization of resident and infiltrating cells
Authors: Ahlfors E , Jonsson R , Czerkinsky C 
Published: November 2003

SUMMARY
The nature and phenotype of infiltrating cells in DTH-like reactions elicited in the murine oral mucosa have been examined by routine histological and immunohistochemical procedures. During the first few hours that followed buccal challenge with the contact sensitizer oxazolone, a discrete lymphocytic reaction was disclosed in the oral mucosa of animals previously sensitized at skin sites, but was absent in animals that had been sensitized at buccal sites. The early lymphocytic reaction in the oral mucosa of skin-sensitized animals preceded the emergence of CD11+ polymorphonuclear cells (PMN) which was most prominent 8 h after hapten challenge and invaded the whole thickness of the oral epithelium. The PMN rapidly disappeared by 24 h. In contrast, early PMN infiltration was virtually absent in specimens from animals similarly challenged but that had been sensitized at local buccal sites. Irrespective of site of initial sensitization, inflammatory reactions developed in the oral mucosa, being maximal by 24 h. At that stage, CD11+ macrophages were the predominant cell type. Both CD4 and CD8 T lymphocytes were scattered in both lamina propria and epithelium, and their numbers were raised throughout the time period studied (2–168 h). IL-2 receptor expression was maximal 16 h post-challenge, and was paralleled by increased DNA synthesis in CD4+ and CD8+ cells, as demonstrated by paired immunohistoautoradiography. Focal accumulations of mononuclear cells containing IL-2-producing cells were readily detected as early as 2–3 h following local challenge with hapten in animals primed at skin but not at buccal sites. Maximal IL-2 staining was detected at 24 h irrespective of initial sensitization site. Interferon-gamma-producing cells were detected at 8 h post-challenge and remained increased during the first 24 h. MHC class II expression was detected on few oral mucosa cells during the first 4 h following hapten challenge, being mainly confined to dendritic-like cells. Consistent with increased numbers of macrophages, MHC class II expression was most intense in specimens obtained 8–24 h after hapten challenge. Thereafter, MHC class II expression was still observed in specimens obtained as late as 72 h, but was essentially associated with patches of basal keratinocytes. Taken together, these observations support the notion that the murine oral mucosa can serve as the site of expression of locally or remotely induced DTH reactions, but also indicate that the site of initial sensitization can profoundly affect the cellular composition of inflammatory reactions subsequent to local buccal challenge.
Successful induction of severe destructive arthritis by the transfer of in vitro-activated synovial fluid T cells from patients with rheumatoid arthritis (RA) in severe combined immunodeficient (SCID) mice
Authors: Sakata A , Sakata K , Ping H , Ohmura T , Tsukano M , Kakimoto K 
Published: November 2003

SUMMARY
In order to investigate the role of pathogenic T cells in RA, the establishment of an RA model using patients’ T cells is thought to be essential. In this study, multiple and severe destructive arthritis was established by transferring in vitro-stimulated synovial fluid T (SFT) cells from patients with RA through simultaneous injection into knee joint and peritoneal cavity of SCID mice without causing xenogeneic graft-versus-host disease (GVHD). Neither the transfer of unstimulated SFT cells nor sole i.p. injection was sufficient to induce severe arthritis. Interestingly, in contrast with SFT cells, in vitro-activated peripheral blood lymphocytes from RA patients failed to trigger such arthritis, suggesting that pathogenic T cells might be concentrated in synovial fluid of RA patients. This, the first severe arthritis model mimicking RA induced by RA patients’ T cells, is expected to provide important information about RA pathogenesis and a possible therapeutic approach.