bluuebunny/crossref_metadata_2025_split huggingface dataset:
Natural regulatory T cells: number and function are normal in the majority of patients with lupus nephritis
Authors: Yates J , Whittington A , Mitchell P , Lechler R I , Lightstone L , Lombardi G 
Published: October 2008

SummaryCD4+ CD25+ regulatory T cells have been shown to be a vital component of the mechanisms that prevent autoreactivity in mice and also in humans. Previous studies have examined CD4+ CD25hi regulatory T cell frequency and function in patients with systemic lupus erythematosus (SLE) with mixed results. We investigated frequency, phenotype and function in 21 patients with SLE and six with inactive disease. We found no reduction in frequency of the CD25hi subset, although active disease was associated with an increased proportion of CD4+ CD25+ T cells. When examining function, in the majority of individuals suppression was comparable with controls, although cells isolated from one patient with active disease failed to suppress proliferation. On testing the effect of CD25hi depletion on the responses of whole peripheral blood mononuclear cells to nucleosomes we found that, where a response was detectable from patients, depletion augmented interferon-γ secretion, demonstrating intact suppression of responses implicated in the pathogenesis of SLE. Our results did not confirm an association of failure in CD4+ CD25hi regulatory T cell function or a reduction in their frequency with active disease. Instead, perturbations in the CD4+ CD25hi regulatory T cell population may play a role in disease in only a minority of the patients afflicted by the diverse syndromes of SLE.
Effect of intestinal microbiota on the induction of regulatory CD25+ CD4+ T cells
Authors: Ishikawa H , Tanaka K , Maeda Y , Aiba Y , Hata A , Tsuji N M , Koga Y , Matsumoto T 
Published: October 2008

SummaryWhen oral tolerance was induced in either specific pathogen-free (SPF) or germ-free (GF) mice, ovalbumin (OVA) feeding before immunization induced oral tolerance successfully in SPF mice. On the other hand, OVA-specific immunoglobulin G1 (IgG1) and IgE titres in OVA-fed GF mice were comparable to those in phosphate-buffered saline-fed GF mice, thus demonstrating that oral tolerance could not be induced in GF mice. The frequencies of CD25+ CD4+/CD4+ cells in the mesenteric lymph node (MLN) and the absolute number of CD25+ CD4+ cells in the Peyer's patches and MLN of naive GF mice were significantly lower than those in naive SPF mice. In an in vitro assay, the CD25+ CD4+ cells from the naive SPF mice suppressed more effectively the proliferation of responder cells in a dose-dependent manner than those from the GF mice. In addition, the CD25+ CD4+ regulatory T (Treg) cells from the naive SPF mice produced higher amounts of interleukin (IL)-10 and transforming growth factor (TGF)-β than those from the GF mice. When anti-TGF-β neutralizing antibody, but not anti-IL-10 neutralizing antibody, was added to the in vitro proliferation assay, the suppressive effect of the CD25+ CD4+ Treg cells from the SPF mice was attenuated to the same level as that of the CD25+ CD4+ cells from the GF mice. In conclusion, the TGF-β-producing CD25+ CD4+ Treg cells from the MLN of SPF mice played a major role in oral tolerance induction. In addition, as the regulatory function of the CD25+ CD4+ cells from the naive GF mice was much lower than that of the CD25+ CD4+ Treg cells from the SPF mice, indigenous microbiota are thus considered to contribute to the induction and maintenance of CD25+ CD4+ Treg cells.
Identification and characterization of Mycobacterium tuberculosis antigens in urine of patients with active pulmonary tuberculosis: an innovative and alternative approach of antigen discovery of useful microbial molecules
Authors: Kashino S S , Pollock N , Napolitano D R , Rodrigues Jr V , Campos-Neto A 
Published: October 2008

Summary
Despite the clear need to control tuberculosis, the diagnosis and prevention of this serious disease are poorly developed and have remained fundamentally unchanged for more than 50 years. Here, we introduce an innovative approach to directly identify Mycobacterium tuberculosis antigens produced in vivo in humans with tuberculosis. We combined reversed phase high performance liquid chromatography and mass spectrometry and categorize four distinct M. tuberculosis proteins produced presumably in lung lesions and excreted in the urine of patients with pulmonary tuberculosis. The genes (MT_1721, MT_1694, MT_2462 and MT_3444) coding for these proteins were cloned and the recombinant molecules were produced in Escherichia coli. The proteins were recognized by immunoglobulin G antibodies from tuberculosis patients but not from non-diseased subjects. In addition, the recombinant proteins were recognized strongly by peripheral blood mononuclear cells from healthy purified protein derivative of tuberculin-positive individuals and to a lesser extent from patients with tuberculosis. These molecules are the only proteins reported to date that are derived directly from bodily fluids of tuberculosis patients, therefore are interesting candidate antigens for the development of vaccine and/or antigen detection assay for accurate diagnosis of active tuberculosis.
In vivotransmigrated monocytes from patients with stable coronary artery disease have a reduced expression of CD11b
Authors: Paulsson J M , Dadfar E , Held C , Jacobson S H , Lundahl J 
Published: October 2008

SummaryCoronary artery disease (CAD) is characterized by infiltration of monocyte derived cells in the intima of the vessel wall. We hypothesized that accumulation of these cells is caused partly by an altered monocyte transmigration process in CAD. To gain insight into this issue we applied the skin blister method that allows collection of in vivo transmigrated cells at sites of local inflammation. Nineteen patients with stable CAD and 19 matched controls were enrolled. Markers of inflammation and gradients of chemokines, as well as adhesion molecule expression and up-regulation capacity, were studied. The expression of inflammatory markers, such as C-reactive protein, interleukin (IL)-6, tumour necrosis factor-α and IL-10, was similar in patients and controls, indicating that patients were in a stable phase of the disease. Expression of adhesion molecules, CD11b and very late activation antigen-4, on peripheral monocytes did not differ between patients and controls. However, following in vivo transmigration, monocytes in patients with CAD had a significantly reduced expression and mobilization of CD11b. The effect on CD11b could not be reproduced by in vitro stimulation with blister fluid, representing a local inflammatory milieu, or in an in vitro system of transmigration. These findings point towards differences in monocyte CD11b expression and availability at an inflammatory site between patients with CAD and healthy controls.
Involvement of retinoic acid-inducible gene-I in inflammation of rheumatoid fibroblast-like synoviocytes
Authors: Imaizumi T , Arikawa T , Sato T , Uesato R , Matsumiya T , Yoshida H , Ueno M , Yamasaki S , Nakajima T , Hirashima M , Sakata K , Ishibashi Y , Toh S , Ohyama C , Satoh K 
Published: October 2008

Summary
Interferon (IFN)-γ is a major cytokine that regulates T helper 1-type immune reactions and serves as an important mediator in the pathogenesis of autoimmune diseases. Retinoic acid-inducible gene-I (RIG-I) is an IFN-γ-inducible gene and known to be involved in the inflammatory and immune reactions. In the present study, we found high levels of RIG-I expression in synovial tissues of rheumatoid arthritis (RA), while the expression in osteoarthritis tissues was low. Treatment of cultured fibroblast-like synoviocytes with IFN-γ markedly induced the expression of RIG-I. Knockdown of RIG-I in fibroblast-like synoviocytes, with specific siRNA, resulted in the inhibition of the IFN-γ-induced expression of chemokine (C-X-C motif) ligand 10 (CXCL10)/IFN-γ-inducible protein-10 (IP-10), a chemokine with chemotactic activity towards T cells. These findings suggest that RIG-I may play an important role in the pathogenesis of synovial inflammation in RA, at least in part, by regulating the IFN-γ-induced expression of CXCL10/IP-10.
Reduction of forkhead box P3 levels in CD4+CD25high T cells in patients with new-onset systemic lupus erythematosus
Authors: Zhang B , Zhang X , Tang F , Zhu L , Liu Y 
Published: October 2008

Summary
The aim of this study was to quantify and evaluate the forkhead box P3 (FoxP3) expression regulatory T cells in new-onset systemic lupus erythematosus (SLE) patients before and after treatment. Forty-four newly diagnosed and untreated SLE patients, including 24 with active disease (SLEDAI ≥ 10) and 20 with inactive disease (SLEDAI &lt; 5), were enrolled in this study. Twenty-one age- and sex-matched healthy volunteers were also included as controls. Peripheral blood samples were collected and mononuclear cells isolated. The expression of CD25 and FoxP3 in CD4+ T cells were analysed with flow cytometry. CD4+CD25+ (3·95–13·04%) and CD4+CD25high (0·04–1·34%) T cells in peripheral blood in untreated patients with new-onset active lupus were significantly lower than that in the patients with inactive lupus (7·27–24·48%, P &lt; 0·05 and 0·14–3·07% P &lt; 0·01 respectively) and that in healthy controls (5·84–14·84%, P &lt; 0·05). Interestingly, the decrease in CD4+CD25high T cells was restored significantly in patients with active lupus after corticosteroid treatment. There was, however, a significantly higher percentage of CD4+FoxP3+ T cells in patients with active (5·30–23·00%) and inactive (7·46–17·38%) new-onset lupus patients compared with healthy control subjects (2·51–12·94%) (P &lt; 0·01). Intriguingly, CD25 expression in CD4+FoxP3+ T cells in patients with active lupus (25·24–62·47%) was significantly lower than that in those patients with inactive lupus (30·35–75·25%, P &lt; 0·05) and healthy controls (54·83–86·38%, P &lt; 0·01). Most strikingly, the levels of FoxP3 expression determined by mean fluorescence intensity in CD4+CD25high cells in patients with active SLE were significantly down-regulated compared with healthy subjects (130 ± 22 versus 162 ± 21, P = 0·012). CD4+CD25high T cells are low in new-onset patients with active SLE and restored after treatment. Despite that the percentage of CD4+FoxP3+ T cells appear high, the levels of FoxP3 expression in CD4+CD25high T cells are down-regulated in untreated lupus patients. There is a disproportional expression between CD25high and FoxP3+ in new-onset patients with active SLE.
Involvement of gaseous low molecular monoxides in the cutaneous reverse passive Arthus reaction: cytoprotective action of carbon monoxide
Authors: Shimizu K , Bae S J , Hara T , Iwata Y , Yamaoka T , Komura K , Muroi E , Takenaka M , Ogawa F , Sato S 
Published: October 2008

SummaryThe deposition of immune complexes (IC) induces an acute inflammatory response with tissue injury, for which the involvement of nitric oxide (NO) and carbon monoxide (CO) has been suggested. NO is induced by NO synthase (NOS) and CO is generated by haeme oxygenase (HO). Among HO isoenzymes, HO-1 is an induced type. To assess the role of NO and CO in the pathogenic process, the cutaneous reverse passive Arthus reaction was examined using NOS inhibitor, HO-1 stimulator and HO-1 inhibitor. To evaluate the reaction we considered oedema, tumour necrosis factor-α, interleukin-6, and neutrophil number. The values of these four parameters were significantly reduced in mice treated with HO-1 stimulator as compared with the positive control mice. Quite the reverse was observed in mice treated with HO-1 inhibitor. These results suggest that the HO-1/CO signalling pathway is a therapeutic target for human IC-mediated disease.
Systemic humoral immunity to non-typeable Haemophilus influenzae
Authors: King P T , Ngui J , Gunawardena D , Holmes P W , Farmer M W , Holdsworth S R 
Published: October 2008

Summary
Non-typeable Haemophilus influenzae (NTHi) is a major cause of respiratory but rarely systemic infection. The host defence to this bacterium has not been well defined in patients with chronic airway infection. The aim of this study was to assess the effect of humoral immunity in host defence to NTHi. Responses were measured in control and bronchiectasis subjects who had recurrent bronchial infection. Antibody and complement-mediated killing was assessed by incubating NTHi with serum and the role of the membrane–attack complex and classical/alternate pathways of complement activation measured. The effect of one strain to induce protective immunity against other strains was assessed. The effect of antibody on granulocyte intracellular killing of NTHi was also measured. The results showed that both healthy control subjects and bronchiectasis patients all had detectable antibody to NTHi of similar titre. Both groups demonstrated effective antibody/complement-mediated killing of different strains of NTHi. This killing was mediated through the membrane–attack complex and the classical pathway of complement activation. Immunization of rabbits with one strain of NTHi resulted in protection from other strains in vitro. Antibody activated granulocytes to kill intracellular bacteria. These findings may explain why NTHi rarely causes systemic disease in patients with chronic respiratory mucosal infection and emphasize the potential importance of cellular immunity against this bacterium.
A dendritic cell-based tumour vaccine for lung cancer: full-length XAGE-1b protein-pulsed dendritic cells induce specific cytotoxic T lymphocytesin vitro
Authors: Zhou Q , Guo A-L , Xu C-R , An S-J , Wang Z , Yang S-Q , Wu Y-L 
Published: October 2008

SummaryXAGE-1b is regarded as one of the most immunogenic antigens and the most promising targets for lung adenocarcinoma immunotherapy. In this study, we sought to determine whether monocyte-derived dendritic cells (DCs) pulsed with purified full-length XAGE-1b could induce specific cytotoxic T lymphocytes (CTLs) against tumour cells from patients with non-small cell lung cancer (NSCLC) in vitro. XAGE-1b mRNA expression was examined in primary cultures of lung cancer cells and normal lung epithelial cells established from fresh tissues surgically resected from 30 patients with NSCLC using reverse transcription–polymerase chain reaction (RT–PCR). XAGE-1b mRNA expression was observed in 11 of 18 (61·1%) adenocarcinomas and one of 12 (8·3%) lung cancers of other histological types (P = 0·015). The 246-base pairs XAGE-1b gene was inserted into a recombinant expression vector. Full-length XAGE-1b was then expressed in BL21 (DE3) Escherichia coli and purified by AKTA-fast performance liquid chromatography (FPLC). DCs generated from peripheral blood mononuclear cells were pulsed with XAGE-1b by incubation with the protein at an immature stage. The XAGE-1b-pulsed DCs induced CTLs following 14 days of co-culture. Finally, an adherent target detachment (ATD) assay was performed to test the cytotoxicity of the XAGE-1b-specific CTLs against cancer cells and normal lung epithelial cells. The XAGE-1b-specific CTLs had a stronger lytic effect on autologous XAGE-1b mRNA-positive cancer cells than on autologous XAGE-1b mRNA-negative cancer cells or allogenous XAGE-1b mRNA-positive cancer cells. The CTLs had no lytic activity against normal lung epithelial cells. These results can be used to develop simple and effective cancer/testis antigen-based immunotherapies for NSCLC.
Immunoglobulin E antibodies from pancreatic cancer patients mediate antibody-dependent cell-mediated cytotoxicity against pancreatic cancer cells
Authors: Fu S L , Pierre J , Smith-Norowitz T A , Hagler M , Bowne W , Pincus M R , Mueller C M , Zenilman M E , Bluth M H 
Published: October 2008

Summary
In addition to allergy and parasitic infections, immunoglobulin E (IgE) has been shown recently to possess anti-viral and anti-cancer effects. We investigated serum levels of IgE, its low-affinity receptor, soluble CD23 (sCD23) in patients with pancreatic cancer and the effect of IgE against pancreatic cancer cells. Twelve patients were evaluated for pancreatic cancer by imaging and confirmed by biopsy. Fifteen healthy volunteers served as controls. Serum Igs (IgG, IgM, IgA, IgE) and sCD23 levels were determined (enzyme-linked immunosorbent assay, nephelometry) and the presence of cancer-specific IgE was assessed (fluorescence microscopy, Western blot). IgE anti-cancer activity was determined by antibody-dependent cell-mediated cytotoxicity (ADCC). Serum levels of IgE and sCD23 were elevated significantly in patients with pancreatic cancer versus controls, whereas no differences were observed in other Ig isotypes (IgG, IgM, IgA). Flow cytometry and immunofluorescence microscopy demonstrated similar presence of IgG and IgE pancreatic cancer Igs. However, Western blot analysis indicated differences in IgG and IgE antigen-specific antibodies; IgE antibody recognized a 50 kD protein. ADCC studies demonstrated that serum and purified IgE-mediated cytotoxicity against pancreatic cancer cells, effects which were reversed with anti-IgE neutralizing antibody and IgE depletion (immunoaffinity); greater cytotoxicity was observed in patient serum when compared with healthy controls. These data suggest that IgE and sCD23 may serve as useful biomarkers for patients with pancreatic cancer and may be important in the immune response to this disease in that IgE-directed therapy may help to direct treatment.
May genetic factors in fibromyalgia help to identify patients with differentially altered frequencies of immune cells?
Authors: Carvalho L S C , Correa H , Silva G C , Campos F S , Baião F R , Ribeiro L S , Faria A M , D'Avila Reis D 
Published: October 2008

SummaryThere is common agreement that fibromyalgia (FM) is an extremely heterogeneous entity. Patients differ in their clinical symptoms, endocrine and immune parameters. In this study we evaluated endocrine and immunological features of distinct subsets of FM patients. In contrast to previous attempts to identify subsets of FM patients, based solely on their psychological and cognitive features, herein we propose to separate FM patients by genetic features. Allelic expression of the polymorphic promoter region of the serotonin transporter (5-HTTLPR) was analysed as a relevant genetic factor for FM. Seventy-five patients meeting the American College of Rheumatology criteria and 27 healthy age-matched controls participated in this study. All controls and FM patients were submitted to genotyping of 5-HTTLPR. Twenty-seven FM patients, who were able to discontinue hypnotic, sedative or psychotropic prescription medications for at least 2 weeks, were then subdivided into L (homozygote LL) or S groups (genotypes LS and SS). They were evaluated for salivary cortisol levels, absolute number of leucocyte subpopulations, including natural killer (NK) cells and activated T and B lymphocytes. Both groups presented decreased cortisol levels, more intense in the L group, increased all B lymphocytes subsets and reduced CD4+CD25high T lymphocytes. The L group had increased CD4+CD25low activated T lymphocytes, while the S group displayed elevated CD4+human leucocyte antigen D-related (HLA-DR)+ activated T lymphocytes and decreased NK cells. We demonstrate that genetic factors may help to identify FM individuals with differentially altered frequencies of immune cells.
Stabilization of dissolved organic matter by aluminium: a toxic effect or stabilization through precipitation?
Authors: Scheel T. , Jansen B. , Van Wijk A. J. , Verstraten J. M. , Kalbitz K. 
Published: October 2008

SummaryCarbon mineralization in acidic forest soils can be retarded by large concentrations of aluminium (Al). However, it is still unclear whether Al reduces C mineralization by direct toxicity to microorganisms or by decreased bioavailability of organic matter (OM) because dissolved organic matter (DOM) is precipitated by Al. We conducted an incubation experiment (6 weeks) with two DOM solutions (40 mg C litre−1) derived from two acidic forests and possessing large differences in composition. Aluminium was added to the solutions in realistic ranges for acidic soils (1.6–24 mg Al litre−1) at pHs of 3.8 and 4.5, to achieve differences in Al speciation. We determined different Al species, including the potentially toxic Al3+, by Diffusive Gradients in Thin Films (DGT) to evaluate toxic effects on microorganisms. Precipitation of OM increased with larger amounts of added Al and higher pH, and we measured a larger fraction of dissolved ‘free’ Al at pH 3.8 than at pH 4.5. Organic matter degradation decreased significantly with Al addition, and we found more organic matter degraded at pH 3.8 than at pH 4.5 for the respective Al additions. Consequently, the observed reduction in OM degradation (i.e. stabilization) cannot be explained by toxic effects of ‘free’ Al. However, C stabilization correlated significantly with C precipitation. The pH did not influence C stabilization directly, but determined the amount of C being precipitated. Phosphorus was removed along with OM by precipitation, which possibly also affected C stabilization. We conclude that C stabilization upon Al addition did not result from toxic effects, but was caused by reduced bioavailability of OM after its precipitation. The reduction in OM degradation by 65% is of great relevance for the overall C stabilization in acidic forest soils. Increasing pH and decreasing Al concentrations upon recovery from acidic deposition should therefore not result in decreased stabilization of precipitated OM.
Drought‐induced tree death in savanna
Authors: FENSHAM R. J. , FAIRFAX R. J. , WARD D. P. 
Published: October 2008

AbstractIncreasing densities of woody plants in savannas has been attributed to both elevated atmospheric CO2 and reduced burning with grazing management, such that the biome could represent a substantial carbon sink. However, we show that extreme droughts (less than two‐thirds expected rainfall over 3 years) occur in the drier half of the savanna biome and can cause substantial tree death. An Australian case study reveals that a net increase in tree cover over five decades of above‐average rainfall was offset by sudden tree death during drought. The relationship between woody cover change and rainfall is moderated by competition with growth being facilitated by low woody cover and drought‐induced death more likely as the woody component of savanna increases. The results are not supportive of a sustained increase in the woody component of xeric savannas resulting from CO2 fertilization or land management. Extensive tree death in savanna regions will become a stark consequence of climate change if predictions of increasing severity and frequency of drought are realized.