bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunophenotypic characterization of peripheral T lymphocytes inMycobacterium tuberculosisinfection and disease
Authors: RODRIGUES D S S , MEDEIROS E A S , WECKX L Y , BONNEZ W , SALOMÃO R , KALLAS E G 
Published: March 2003

SUMMARYThe cellular immune response probably plays a pivotal role in determining the clinical outcome after exposure to Mycobacterium tuberculosis. We used multi-parameter flow-cytometry to evaluate the distribution of T-lymphocyte subsets during infection and disease caused by M. tuberculosis. Samples were obtained from 71 volunteers to identify the T CD4+ and CD8+ lymphocyte numbers, and the activation plus memory/naïve phenotypes, as defined by CD38, HLA-DR, CD45RA and CD27 markers. Subjects were divided into 18 healthy volunteers without detectable reaction to purified protein derivative (PPD−), 18 health care workers with a recent conversion to PPD, 20 patients with active pulmonary tuberculosis (TBC) and 15 patients with treated TBC at 6 months of therapy. By multiple-comparison analyses, the T CD4+ lymphocyte number of the TBC group was lower than the PPD– group (P &lt; 0·05). This difference was apparently lost after treatment. The higher and the lower number of naïve T CD4+ cells was observed in the PPD– and TBC group, respectively. CD8+ T lymphocytes were also statistically different among the four groups (P = 0·0002), lower in the TBC group (P &lt; 0·05). CD8+ T lymphocyte activation was evaluated by the CD38 and HLA-DR surface expression. The percentage distribution of these markers was statistically different between the four groups (P = 0·0055). TBC patients had a higher percentage of CD38+ cells and mean fluorescence index, suggesting an overall increase of cell activation. These results suggest that peripheral T lymphocytes reflect cellular activation during TBC, along with possible redistribution of naïve, memory/effector and late differentiated memory/effector phenotypes in the peripheral blood after infection and disease caused by M. tuberculosis.
Defective expression and tyrosine phosphorylation of the T cell receptor zeta chain in peripheral blood T cells from systemic lupus erythematosus patients
Authors: PANG M , SETOYAMA Y , TSUZAKA K , YOSHIMOTO K , AMANO K , ABE T , TAKEUCHI T 
Published: March 2003

SUMMARYWe have reported that tyrosine phosphorylation and expression of the T cell receptor zeta chain (TCR ζ) was decreased in two systemic lupus erythematosus (SLE) patients with an abnormal TCR ζ lacking exon-7. To examine further the TCR ζ defect and any possible relationship with specific clinical features, we studied the expression of TCR ζ in peripheral blood T cells from 44 patients with SLE, 53 with other rheumatic diseases (30 rheumatoid arthritis (RA), 11 systemic sclerosis (SSc) and 12 primary Sjögren's syndrome(SjS)) and 39 healthy individuals. Flow cytometric analysis demonstrated a significant decrease in the expression of TCR ζ in SLE (P &lt; 0·001), but not in the other rheumatic diseases. Immunoprecipitation experiments confirmed that the expression of TCR ζ in SLE T cells was decreased dramatically (normal: 111·4 ± 22·6%, SLE: 51·6 ± 37·4%, P &lt; 0·0001). The decrease in TCR ζ did not correlate with disease activity, or with the dose of prednisolone (PSL). There were, however, three SLE patients in whom the level of TCR ζ expression normalized after treatment, suggesting that mechanisms responsible for the TCR ζ defect appear to be heterogeneous. These results confirm the defective expression and altered tyrosine phosphorylation of TCR ζ in a large proportion of SLE patients, suggesting that it may play an important role in T cell dysfunction in SLE.
Kinetics of changes in lymphocyte sub-populations in mouse lungs after intrapulmonary infection withM. bovis(Bacillus Calmette-Guerin) and identity of cells responsible for IFNγ responses
Authors: SAXENA R K , WEISSMAN D , SAXENA Q B , SIMPSON J , LEWIS D M 
Published: March 2003

SUMMARYGamma interferon (IFNγ) plays a key role in host defense against pulmonary mycobacterial infections. A variety of lymphocyte subsets may participate in producing pulmonary IFNγ responses, but their relative contributions after mycobacterial infection have not been clearly elucidated. To address this question, C57Bl/6 female mice were infected by intrapulmonary instillation of 2·5 × 104 BCG (Mycobacterium bovis Bacillus Calmette-Guerin). Lymphocyte populations in lung interstitium were examined at different time points after the infection. BCG load in lungs peaked between 4 and 6 weeks post-infection and declined to very low levels by the 12th week of infection. Recovery of lung interstitial lymphocytes doubled by 4–6 weeks after infection and declined thereafter. Flow cytometric analysis of the lung-derived lymphocytes revealed that about 5% of the these cells made IFNγ in control mice, and this baseline IFNγ production involved T (CD3+NK1.1−), NK (CD3−NK1.1+) and NKT (CD3+NK1.1+) cells. As the BCG lung infection peaked, the total number of CD3+ T cells in the lungs increased threefold at 5–6 weeks post-infection. There was a marked increase (sixfold) in the number of T cells secreting IFNγ 5–6 weeks post-infection. Some increase was also noted in the NKT cells making IFNγ, but the numbers of NK cells making IFNγ in BCG-infected lungs remained unaltered. Our results suggest that whereas NK and NKT cells contribute to baseline IFNγ secretion in control lungs, expansion in the IFNγ-producing T-cell population was essentially responsible for the augmented response seen in lungs of BCG-infected mice.
C-ANCA-positive IgG fraction from patients with Wegener's granulomatosis induces lung vasculitis in rats
Authors: WEIDEBACH W , VIANA V S T , LEON E P , BUENO C , LEME A S , ARANTES-COSTA F M , MARTINS M A , SALDIVA P H N , BONFA E 
Published: March 2003

SUMMARYThe aim of the present study was to analyse in rats the ability of C-ANCA-positive IgG fraction in triggering inflammatory response on pulmonary tissue. Wistar rats (n = 18) were injected via the the internal jugular vein with 20 mg of total C-ANCA-positive IgG fraction isolated from serum of three different Wegener's granulomatosis patients obtained before therapy. Similarly, control rats were treated with IgG fraction from two rheumatoid arthritis patients (n = 7), IgG from six normal human sera (n = 15) or saline (n = 18), respectively. Animals were sacrificed after 24h of injection for histological analysis of the lungs. Vasculitis and inflammatory infiltrate were consistently absent in rats injected with rheumatoid arthritis IgG or saline and in 14/15 of normal IgG treated animals. In contrast, marked vasculitis was observed in all 18 animals injected with C-ANCA-positive IgG fraction. The histological features were characterized by the presence of a perivascular pleomorphic cellular sheath, particularly around small vessels, endothelial adherence and diapedesis of polymorphonuclear leucocytes and presence of granuloma-like lesions. A dose–response relationship was observed between protein concentration of C-ANCA IgG sample and the intensity of the inflammatory response in the animals. In addition, IgG fraction with undetectable C-ANCA, obtained from one patient in remission after treatment, was not able to reproduce the pulmonary tissue alterations induced by its paired IgG that was positive for C-ANCA taken before therapy. The experimental model described herein may be useful to characterize more effectively the pathogenic mechanism of C-ANCA in Wegener's disease.
Metallothionein suppresses collagen-induced arthritis via induction of TGF-βand down-regulation of proinflammatory mediators
Authors: YOUN J , HWANG S-H , RYOO Z-Y , LYNES M A , PAIK D-J , CHUNG H-S , KIM H-Y 
Published: March 2003

SUMMARYMetallothionein is a low molecular weight, cysteine-rich, stress response protein that can act as an antioxidant and as an immunosuppressive agent in instances of antigen-dependent adaptive immunity. In this context, we assessed the therapeutic potential and mechanisms of action of metallothionein in a collagen-induced arthritis model. Repeated administration of metallothionein-I + II during the course of disease dramatically reduced the incidence and severity of the disease. Joint tissues isolated from boostered paws of metallothionein-I + II-treated mice expressed significantly reduced levels of proinflammatory mediators, such as tumour necrosis factor (TNF)-α and cyclooxygenase-2, when compared with those of control-treated mice. Lymph node cells obtained from metallothionein-I + II -injected mice exhibited a significant decrease in the proliferative response and a remarkable increase in tumour growth factor (TGF)-β production in response to type II collagen. Taken together, these results suggest that metallothionein-I + II promote the development of type II collagen-specific, TGF-β-producing cells to antagonize the expansion of arthritogenic cells. This could lead to local suppression of inflammatory responses by inhibiting the expression of proinflammatory molecules. Thus, this study demonstrates the suppressive effects of metallothionein on collagen-induced arthritis, and indicates that there may be a potential therapeutic application for manipulation of metallothionein during the treatment of autoimmune disorders.
Immunogenicity ofMycobacterium tuberculosisRD1 region gene products in infected cattle
Authors: MUSTAFA A S , COCKLE P J , SHABAN F , HEWINSON R G , VORDERMEIER H M 
Published: March 2003

SUMMARYCurrent immuno-diagnostic tests for the detection of Mycobacterium bovis infection in cattle rely on the use of tuberculin PPD as antigens. However, the use of a cattle vaccine is effectively prohibited because BCG, the only potentially available cattle TB vaccine, compromises the current tuberculin test. The main objective of this study was to identify specific antigens, which could increase the test sensitivity to levels achieved with tuberculin. Our approach utilized the availability of the genome sequences of Mycobactereium tuberculosis and BCG by applying principles of comparative genomics to the identification of species-specific antigens. Eight open-reading frames (Rv3871 to Rv3878) encoding for putative antigens in the RD1 region of the M. tuberculosis genome, which is deleted in all strains of BCG, were selected and screened in the form of pools of synthetic peptides for immunological reactivity (antigen induced proliferation and IFN-γ secretion) with peripheral blood mononuclear cells from cattle experimentally infected with M. bovis. Our results confirm the immunodominant role of two RD1 region products, CFP-10 (Rv3874) and ESAT-6 (Rv3875). In addition, we were able to identify 3 more antigens (Rv3871, Rv3872 and Rv3873), which induced immunological reactivity in PBMC from more than 50%M. bovis of infected cattle.
Fcγreceptor-mediated phagocytosis ofPlasmodium falciparum-infected erythrocytesin vitro
Authors: TEBO A E , KREMSNER P G , LUTY A J F 
Published: March 2003

SummaryAlthough convincing evidence exists for the role of immunoglobulin G (IgG) antibodies in immunity to malaria, antibody titres do not usually predict protection. In this study we have assessed the interaction between Plasmodium falciparum-infected erythrocytes (PE), opsonized with immune serum containing different amounts of IgG antibody isotypes, with either THP-1 cells, ex-vivo human monocytes or IIAI.6 transfectant cells expressing FcγRIIa-Arg/Arg131 or –His/His131 allotypes. Our results show that PMA-treated THP-1 cells were capable of phagocytosing serum-opsonized PE by FcγRI (CD64) and FcγRIIa (CD32), acting synergistically. The known FcγRIIa polymorphism motivated us to examine its influence  on  IgG  isotype-mediated  phagocytosis  of  opsonized  PE  with  human  monocytes  and  the IIAI.6 transfectant cells expressing either allelic forms. Regardless of the cell type, PE phagocytosis with FcγRIIa-His/His131 was highest following opsonization with a predominantly IgG3-containing immune serum pool. In contrast, PE phagocytosis with FcγRIIa-Arg/Arg131 tended to be higher with an IgG1-containing pool. These results suggest a genetically determined influence of effector cell phenotype on IgG antibody–pathogen interaction in P. falciparum malaria.
Risk factors in HIV-1-infected patients developing repetitive bacterial infections: toxicological, clinical, specific antibody class responses, opsonophagocytosis and Fcγ  RIIa polymorphism characteristics
Authors: PAYERAS A , MARTINEZ P , MILà J , RIERA M , PAREJA A , CASAL J , MATAMOROS N 
Published: March 2003

Summary
The aim of the study was to determine possible factors related to the risk of developing recurrent bacterial respiratory tract infections in HIV-1-infected patients, regardless of the degree of immune cellular impairment. Thirty-three HIV-1 seropositive patients with previous repetitive bacterial respiratory tract infections (case group), 33 HIV-1 seropositive controls (matched by CD4-cell counts) without these antecedents and 27 healthy controls were studied before and after administration of pneumococcal and Haemophilus influenzae type b vaccines. Clinical or toxicological variables, cutaneous tests, complement factors, beta2-microglobulin, serum IgM, IgA, IgG and subclasses, specific antibodies (IgG, IgG2, IgA) against pneumococcal vaccine and polyribosylribitol phosphate (PRP), their avidity, opsonophagocytosis and IgG2m and FcγRIIa allotypes were determined. A history of drug abuse (P = 0·001), less likelihood of receiving high activity antiretroviral treatment high activity antiretroviral treatment (HAART) (P = 0·01), higher levels of HIV-1 viral load (P &lt; 0·05), serum IgG (P &lt; 0·01) and beta2-microglobulin (P &lt; 0·01) were observed in the case group. Also, a lower increase in specific antibodies to pneumococcal vaccine and PRP was demonstrated in the cases in comparison with the two control groups. No differences were observed in the avidity of antibodies, opsonophagocytic capacity or IgG2m and FcγRIIa allotypes between the three groups. These data indicate that vaccination strategies against encapsulated bacteria can be unsuccessful in the HIV-1-infected patients presenting repetitive bacterial respiratory tract infections if behavioural aspects or measures to improve adherence to HAART therapies are not considered.
Gangliosides inhibit the development from monocytes to dendritic cells
Authors: WöLFL M , BATTEN W Y , POSOVSZKY C , BERNHARD H , BERTHOLD F 
Published: March 2003

SummaryDendritic cell (DC) development and function is critical in the initiation phase of any antigen-specific immune response against tumours. Impaired function of DC is one explanation as to how tumours escape immunosurveillance. In the presence of various soluble tumour-related factors DC precursors lose their ability to differentiate into mature DC and to activate T cells. Gangliosides are glycosphingolipids shed by tumours of neuroectodermal origin such as melanoma and neuroblastoma. In this investigation we address the question of whether gangliosides suppress the development and function of monocyte-derived DC in vitro. In the presence of gangliosides, the monocytic DC precursors showed increased adherence, cell spreading and a reduced number of dendrites. The expression of MHC class II molecules, co-stimulatory molecules and the GM-CSF receptor (CD116) on the ganglioside-treated DC was significantly reduced. Furthermore, the function of ganglioside-treated DC was impaired as observed in endocytosis, chemotactic and T cell proliferation assays. In contrast to monocytic DC precursors, mature DC were unaffected even when higher doses of gangliosides were added to the culture. With regard to their carbohydrate structure, five different gangliosides (GM2, GM3, GD2, GD3, GT1b), which are typically shed by melanoma and neuroblastoma, were tested for their ability to suppress DC development and function. Suppression was induced by GM2, but not by the other gangliosides. These data suggest that certain gangliosides impair DC precursors, implying a possible mechanism for tumour escape.
Anti-ribosomal antibodies from lupus patients bind DNA
Authors: CAPONI L , CHIMENTI D , PRATESI F , MIGLIORINI P 
Published: March 2003

SummaryAntibodies specific for ribosomal P proteins (anti-P) are a hallmark of systemic lupus as anti-DNA antibodies are. It has been reported that anti-P antibodies are more frequently detected in anti-dsDNA positive sera. The aim of the present study was to verify the binding ability of anti-P antibodies towards polynucleotides and nucleosomes. We purified anti-P antibodies from 8 SLE patients' sera and we analysed them by ELISA on plates coated with DNA or nucleosomes. We performed also inhibition experiments in order to verify the specificity of the binding. All the purified anti-P antibodies bound DNA, but some anti-DNA binding activity remained among the non-anti-P antibodies in the flow through. Only half of the purified antibodies bound to nucleosomes, and anti-nucleosomal activity was demonstrated also in non anti-P antibody fraction. The inhibition experiments performed on two anti-P antibodies pointed out that only the homologous antigen inhibited the binding to either P peptide or DNA coated onto the solid phase. These results show that sera in which the two specificities coexist contain antibodies endowed with a double binding ability for DNA and the P peptide.
Atorvastatin suppresses interferon-γ-induced neopterin formation and tryptophan degradation in human peripheral blood mononuclear cells and in monocytic cell lines
Authors: NEURAUTER G , WIRLEITNER B , LAICH A , SCHENNACH H , WEISS G , FUCHS D 
Published: March 2003

SUMMARY
Inhibitors of 3-hydroxy-3methylglutaryl-co-enzyme A (HMG-CoA) reductase, so-called statins, are used in medical practice because of their lipid-lowering effect and to reduce the risk of coronary heart disease. Recent findings indicate that statins also have anti-inflammatory properties and can modulate the immune response. In vitro, we investigated the effect of atorvastatin on the T cell/macrophage system in peripheral blood mononuclear cells (PBMC) and in the human monocytic cell lines THP-1 and MonoMac6. We monitored neopterin production and tryptophan degradation in PBMC after treatment with 10 µm and 100 µm atorvastatin in the presence or absence of 100 U/ml IFN-γ, 10 µg/ml phytohaemagglutinin (PHA) or 10 µg/ml concanavalin A (ConA) and in monocytic cell lines THP-1 and MonoMac6 with or without stimulation with 100 U/ml IFN-γ or 10 ng/ml to 1 µg/ml lipopolysaccharide (LPS). In stimulated PBMC 100 µm atorvastatin inhibited neopterin formation and tryptophan degradation completely, whereas 10 µm atorvastatin was only partially effective. Also in monocytic cell lines THP-1 and MonoMac6, atorvastatin was able to suppress IFN-γ- and LPS-induced formation of neopterin and degradation of tryptophan. Our data from PBMC agree well with previous investigations that statins inhibit T cell activation within the cellular immune response. In addition we demonstrate that atorvastatin directly inhibits IFN-γ-mediated pathways in monocytic cells, suggesting that both immunoreactivity of T cells and of monocyte-derived macrophages are down-regulated by this statin.
Antigen inhibition of collagen-induced arthritis is associated with up-regulation of IL-4 mRNA and induction of Ox40 on T cells in draining lymph nodes
Authors: MATTSSON L , LUNDBERG K , MÜSSENER E , JANSSON A , ERLANDSSON HARRIS H , LARSSON P 
Published: March 2003

SUMMARYThe addition of a foreign antigen to an inoculum completely inhibits the development of collagen-induced arthritis (CIA). However, the mechanism of this phenomenon, antigen -inhibition, is incompletely understood. Previous studies have demonstrated that the inhibition of arthritis is not mediated through suppression of the antibody response to cartilage antigens. In this paper we investigated cytokine mRNA levels in lymph nodes cells recovered 3, 7 or 16 days from animals immunized with either collagen II in IFA or OVA + collagen II in IFA. At day 7, but not at other time-points, IL-4 mRNA was up-regulated in the lymph nodes of OVA-inhibited non-arthritic animals compared to control animals which all developed arthritis. No significant differences between the two groups could be detected when expression of IFN-γ, IL-2, TNF-α, IL-1β or IL-10 mRNA was analysed. Flow cytometry analysis of draining lymph node cells demonstrated that the T cell marker Ox40 was up-regulated in the OVA-inhibited group. Our results indicate that the complete inhibition of CIA caused by addition of OVA to the collagen II inoculum is due to the presence of a TH2 environment resulting from an increased production of IL-4 mRNA and a parallel increase in Ox40+ T cells.
Role of interleukin-12 in the regulation of CD4+ T cell apoptosis in a mouse model of asthma
Authors: KODAMA T , KURIBAYASHI K , NAKAMURA H , FUJITA M , FUJITA T , TAKEDA K , DAKHAMA A , GELFAND E W , MATSUYAMA T , KITADA O 
Published: March 2003

SUMMARYAllergic asthma, a chronic inflammatory disease of the airways, is characterized by the presence of T helper 2 cells and eosinophils in sputum, bronchoalveolar lavage, and mucosal biopsy specimens. Although the T helper 1-promoting cytokine, interleukin-12, is capable of inhibiting the T helper 2-driven asthma symptoms and bronchial responsiveness, the specific mechanisms underlying these interleukin-12 actions are unclear. The anti-allergic response to interleukin-12 is only partially dependent on interferon-γ, which induces apoptosis by enhancing expression of Fas antigen. We therefore investigated in vivo whether the anti-allergic action of interleukin-12 is mediated through induction of apoptosis. C57BL/6 mice immunized to ovalbumin by intraperitoneal injection were challenged three times with an ovalbumin aerosol every second day for 7 days. Recombinant interleukin-12 was administered intravenously after the final challenge. After the last ovalbumin challenge, mice were examined for effects of interleukin-12 on inflammatory cell infiltration and apoptosis in the lung as detected by terminal deoxynucleotidyl transferase-mediated deoxyribonucleoside triphosphate nick end-labelling.Administration of interleukin-12 reduced ovalbumin-induced pulmonary eosinophilia (P &lt; 0·01) and CD4+ T cell infiltration (P &lt; 0·01). Moreover, treatment with interleukin-12 shortly after ovalbumin inhalation resulted in both increased interferon-γ production (P &lt; 0·01) and enhanced apoptosis of CD4+ T cells in allergic airway infiltrates (P &lt; 0·05). These results suggest that the beneficial effects of interleukin-12 in asthma may include enhancement of apoptosis of CD4+ T cells in airways.