bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody responses to a C-terminal fragment of thePlasmodium falciparumblood-stage antigen Pf332 in Senegalese individuals naturally primed to the parasite
Authors: Israelsson E , Balogun H , Vasconcelos N-M , Beser J , Roussilhon C , Rogier C , Trape J F , Berzins K 
Published: July 2010

SummaryPrevious studies have shown that antibodies from humans exposed continuously to malaria recognize the Plasmodium falciparum asexual blood-stage antigen Pf332. Here we analysed the antibody responses to a C-terminal fragment of Pf332, designated C231, in individuals from Senegal, by measuring the serum levels of immunoglobulin M (IgM), IgG class and subclass and IgE antibodies. IgG antibody reactivity with crude P. falciparum antigen was detected in all the donors, while many of the children lacked or had low levels of such antibodies against C231. The antibody levels increased significantly with age for both crude P. falciparum antigen and C231, and in the older age groups most of the donors displayed antibodies to C231. This was also true for IgM, IgE and IgG subclass reactivity against C231. Moreover, the ratio of IgG1/IgG2 was considerably lower for C231 than for crude P. falciparum antigen, and in age groups 10–14 and 15–19 years the levels of IgG2 against C231 even exceeded that of IgG1. The IgG2/IgG3 ratios suggest that C231 gives similar levels of IgG2 and IgG3, except for children aged 4–9 years, where IgG3 was higher. Raw IgM, IgG class and subclass and IgE antibody levels to C231 tended to be higher in those who did not experience a malaria attack, but following linear multivariate analysis the trends were not significant.
Analysis of regulatory T cell associated forkhead box P3 expression in the lungs of patients with sarcoidosis
Authors: Idali F , Wahlström J , Müller-Suur C , Eklund A , Grunewald J 
Published: July 2010

Summary
In pulmonary sarcoidosis, the typical T helper 1-mediated immune response in the lungs has been proposed to be co-ordinated by regulatory T cells; however, their exact role needs to be clarified. We used real-time polymerase chain reaction to study genes involved in regulatory T cell functions in CD4+ T cells isolated from bronchoalveolar lavage fluid (BALF) of patients (n = 24) and healthy subjects (n = 7). The genes included the transcription factor forkhead box P3 (FoxP3), interleukin (IL)-10, transforming growth factor-β1 and chemokine receptor 2 (CCR2). The same genes were also studied in isolated BALF CD4+ T cell receptor AV2S3+ and AV2S3– T cells of patients with lung-restricted AV2S3 T cell expansions (n = 12). Intracellular staining of the FoxP3 protein was performed additionally in 14 patients and nine healthy subjects. mRNA expression of FoxP3, CCR2 and IL-10 was decreased significantly in BALF CD4+ T cells of patients. Flow cytometric analysis of CD4+ T cells also demonstrated a decreased frequency of FoxP3+ cells in the BALF and blood of sarcoidosis patients as well as a reduced intensity (mean fluorescence intensity) of FoxP3 expression in BALF FoxP3+ cells of patients. BALF CD4+AV2S3+ T cells expressed significantly lower levels of FoxP3 and CCR2 mRNA versus BALF CD4+AV2S3– T cells. The main conclusion of our study is that there is a reduced expression of regulatory T cell associated genes in BALF CD4+ T cells in sarcoidosis. In addition, our data suggest an effector function of AV2S3+ lung-accumulated T cells in sarcoidosis.
Persistent human immunodeficiency virus-1 antigenaemia affects the expression of interleukin-7Rα on central and effector memory CD4+ and CD8+ T cell subsets
Authors: Mercier F , Boulassel M-R , Yassine-Diab B , Tremblay C , Bernard N-F , Sekaly R-P , Routy J-P 
Published: July 2010

Summary
Interleukin (IL)-7 and its receptor (IL-7Rα) play important roles in regulating lymphopoiesis. Previous studies have reported that human immunodeficiency virus-1 (HIV-1) viraemia affects the expression of IL-7Rα, but its effects on CD4+ and CD8+ T cell memory subsets have not been studied. Using eight-colour flow cytometry, we compared the immunophenotypic patterns of CD4+ and CD8+ T cell subsets expressing IL-7Rα and activation markers, as well as circulating IL-7 levels, in three well-defined groups of HIV-1-infected subjects: successfully treated, viraemic and long-term non-progressor (LTNP). Compared with successfully treated and LTNP subjects, viraemic patients had reduced expression of IL-7Rα on both CD4+ and CD8+ T cells, particularly on central and effector memory T cell compartments, and substantially elevated expression of activation markers on CD8+ T cell subsets. Circulating IL-7 levels were correlated negatively with the number of CD4+ and CD8+ T cell subsets expressing IL-7Rα; these associations were stronger with CD4+ T cell subsets and mainly with central and effector memory cells. The expression of activation markers on CD4+ and CD8+ cell T subsets was not related to circulating IL-7 levels. A strong negative correlation was observed between central memory CD4+ or CD8+ T cells expressing IL-7Rα and those expressing activation markers, independently of IL-7 levels. Collectively, these results provide further insight on the role of unsuppressed viral load in disrupting the IL-7/IL-7Rα system and contributing to HIV-1 disease progression.
CDIP-2, a synthetic peptide derived from chemokine (C-C motif) ligand 13 (CCL13), ameliorates allergic airway inflammation
Authors: Mendez-Enriquez E , Melendez Y , Martinez F , Baay G , Huerta-Yepez S , Gonzalez-Bonilla C , Fortoul T I , Soldevila G , García-Zepeda E A 
Published: July 2010

SummaryAirway inflammation is characterized by selective recruitment of mononuclear and granulocytic cells. This recruitment is mediated by the action of chemotactic cytokines, such as chemokines. A number of chemokines and their receptors have been identified and proposed as potential therapeutic agents in allergic airway inflammation. One of these chemokines is chemokine (C-C motif) ligand 13 (CCL13), a CC chemokine that has been associated with allergic inflammatory diseases such as asthma and allergic rhinitis. To investigate alternative therapeutic agents to alleviate allergic inflammatory diseases, a number of chemokine-derived synthetic peptides were designed and tested for their ability to modulate in vitro and in vivo chemokine-mediated functions. Our results show that one of these peptides, CDIP-2, displayed antagonist functions in in vitro chemotaxis assays using monocytic cell lines. In addition, we found that CDIP-2 significantly reduced peribronchial, perivascular infiltrate and mucus overproduction in an ovalbumin-induced allergic lung inflammation murine model. Thus, CDIP-2 may be considered as part of a novel group of anti-inflammatory agents based on chemokine-derived synthetic peptides.
Rapid subcutaneous immunoglobulin administration every second week results in high and stable serum immunoglobulin G levels in patients with primary antibody deficiencies
Authors: Gustafson R , Gardulf A , Hansen S , Leibl H , Engl W , Lindén M , Müller A , Hammarström L 
Published: July 2010

Summary
Subcutaneous immunoglobulin G (SCIG) infusions as life-long replacement therapy in patients with primary antibody deficiences (PAD) is being applied increasingly. However, only a few published pharmacokinetic studies are available for this route of administration. Therefore, the pharmacokinetics of a 16% immunoglobulin G (IgG) preparation intended for subcutaneous use were investigated in patients with common variable immunodeficiency and X-linked agammaglobulinaemia. SCIG infusions (200 mg/kg body weight) were administered to 12 adult patients every 14 days for 24 weeks (total of 144 infusions). Pharmacokinetic parameters were determined based on serum IgG trough levels and antibody levels against tetanus. The median half-life of the total serum IgG and for the tetanus antibodies was 40·6 and 23·3 days respectively. Median in vivo recovery of serum IgG and tetanus immunoglobulins were 36% and 46% respectively. Median, preinfusion serum IgG trough levels per patient were high without major variations between infusions and ranged from 7·24 to 7·86 g/l. Safety, in terms of adverse events including systemic adverse reactions and local tissue reactions at infusions sites, was monitored throughout the study. Six mild, local tissue reactions were observed during the study in one patient. No systemic adverse reactions related to the study drug were observed and no serious other adverse event occurred during the study. It is concluded that the bi-weekly SCIG therapy was well tolerated in the study and that it results in high and stable serum IgG levels, offering an alternative therapy regimen to patients suffering from PAD.
Intrahepatic endothelial and Kupffer cells involved in immunosuppressive cytokines and natural killer (NK)/NK T cell disorders in viral acute hepatitis
Authors: Jacques A , Bleau C , Martin J-P , Lamontagne L 
Published: July 2010

SummaryDuring acute viral hepatitis, the intrahepatic tolerance sustained by immunosuppressive cytokines such as interleukin (IL)-4, IL-10, transforming growth factor (TGF)-β and prostaglandin E2 (PGE2), produced by Kupffer cells (KC), liver sinusoidal endothelial cells (LSEC), natural killer (NK) T cells and natural regulatory T cells may be disturbed. NK cells are recruited normally in the liver and produce interferon (IFN)-γ to control viral replication. The use of mouse hepatitis virus type 3 (MHV3) attenuated variants showing selected tropisms for KC or LSEC have allowed determining their roles in the disturbances of immune tolerance during viral hepatitis. Groups of C57BL/6 mice were infected with the pathogenic L2-MHV3 (KC+, LSEC+), low attenuated 51·6-MHV3 (KC+, LSEC–) or high attenuated CL12-MHV3 (KC–, LSEC–) variants for the first 3 days. Results showed that IL-10, TGF-β and PGE2 production in the liver decreased in L2-MHV3-infected mice and increased in 51·6-MHV3- and CL12-MHV3-infected mice. The ratio of IFN-γ/IL-4 in liver decreased in L2-MHV3-infected mice, while it was not (or low) altered in mice infected with the attenuated MHV3 variant mice. Phenotypic analysis of intrahepatic mononuclear cells revealed that apoptotic NK and NK T cells increased in mice infected with the L2-MHV3, but were minor in 51·6-MHV3- and CL12-MHV3-infected mice. The numbers of CD4+ forkhead box P3+ cells increased in the livers from low pathogenic CL12-MHV3 and YAC-MHV3-infected mice. These results indicate that viral permissivity of KC and LSEC is involved in the decrease of IL-10 and PGE2, while KC may play an additional role in the apoptosis of NK and NK T cells during acute viral hepatitis.
Atorvastatin does not alter serum levels of sCD95 and sCD95L in multiple sclerosis
Authors: Sellner J , Greeve I , Findling O , Grandgirard D , Leib S L , Mattle H P 
Published: July 2010

SummaryElimination of autoreactive T cells by apoptosis is critical for restricting immune responses to self-antigens. An errant lytic interaction between the CD95 death receptor and its ligand CD95L is presumed to be involved in the pathogenesis of multiple sclerosis (MS). Statins are promising agents for the treatment of MS and were shown to modulate levels of soluble death receptors. Here, we evaluated the in vivo effects by interferon (IFN)-β and atorvastatin on soluble CD95 (sCD95) and sCD95L in serum of patients with MS. Concentrations of sCD95 and sCD95L did not show any differences between MS and healthy control subjects. In patients with MS, treatment with IFN-β increased serum levels of sCD95 and sCD95L significantly (P &lt; 0·01 and P &lt; 0·05 respectively). Addition of atorvastatin to IFN-β did not alter serum levels of sCD95 and sCD95L significantly. Our study suggests that atorvastatin does not affect IFN-β-induced increases of the soluble death receptors in the serum of patients with MS.
The value of serum neopterin, interferon-gamma levels and interleukin-12B polymorphisms in predicting acute renal allograft rejection
Authors: Chin G K , Adams C L , Carey B S , Shaw S , Tse W-Y , Kaminski E R 
Published: July 2010

Summary
Acute rejection remains a poor predictor of graft outcome. In this study, we measured serum levels of interferon (IFN)-γ and neopterin by enzyme-linked immunosorbent assay and a single nucleotide polymorphism (SNP) within the 3′ untranslated region of the interleukin (IL)-12 B gene (1188 A/C) to determine whether either of these factors could predict acute rejection in renal transplantation. Significantly higher early post-transplant neopterin levels (days 5–7; 35·7 versus 19·9 nmol/l) were observed in recipients who subsequently rejected their grafts. Post-transplant neopterin levels showed a strong positive correlation with 1-month creatinine levels (Spearman's correlation 0·62, P &lt; 0·001), suggesting macrophage activation early after transplantation. Pretransplant neopterin and IFN-γ levels and the IL-12B gene SNP did not predict acute rejection in this small retrospective study. The ability to predict acute rejection non-invasively early after transplantation could lead to individual tailoring of immunosuppressive regimens and perhaps lead eventually to longer graft survival.
Redox signalling and the inflammatory response in rheumatoid arthritis
Authors: Filippin L I , Vercelino R , Marroni N P , Xavier R M 
Published: July 2010

Summary
Reactive oxygen species (ROS) are produced mainly during oxidative phosphorylation and by activated phagocytic cells during oxidative burst. The excessive production of ROS can damage lipids, protein, membrane and nucleic acids. They also serve as important intracellular signalling that enhances the inflammatory response. Many studies have demonstrated a role of ROS in the pathogenesis of inflammatory chronic arthropathies, such as rheumatoid arthritis. It is known that ROS can function as a second messenger to activate nuclear factor kappa-B, which orchestrates the expression of a spectrum of genes involved in the inflammatory response. Therefore, an understanding of the complex interactions between these pathways might be useful for the development of novel therapeutic strategies for rheumatoid arthritis.
Depletion of CD4+ CD25+ regulatory T cells inhibits local tumour growth in a mouse model of B cell lymphoma
Authors: Heier I , Hofgaard P O , Brandtzæg P , Jahnsen F L , Karlsson M 
Published: July 2010

SummaryRegulatory T cells (Tregs) may inhibit immunity against cancer. Induction and expansion of Tregs in the immunosuppressive microenvironment created by a growing tumour appear to be one of the mechanisms by which it can evade host defence. We studied the impact of CD25+ Tregs in a B cell lymphoma model in which Rag2–/– mice received adoptive transfer of wild-type spleen cells with or without CD25+ cells, and concurrently subcutaneous inoculation of the B cell lymphoma cell line A20. We also examined the effect of engaging the glucocorticoid-induced tumour necrosis factor receptor (GITR) − an approach reported previously to abrogate the suppressive effects of Tregs. Mice that received spleen cells depleted of CD25+ Tregs showed significantly slower tumour growth and increased survival compared with mice that received unsorted spleen cells. The Treg-depleted group also had significantly more CD8+ T cells infiltrating the tumours and higher levels of serum immunoglobulin G subclasses. The anti-GITR treatment had no significant effect on tumour growth, survival or immunoglobulin production. In the CD25-depleted group four of 10 mice developed clinical signs of autoimmunity, in contrast to none in the non-depleted group. Forkhead box P3+ T cells were found in tumour-draining lymph nodes in mice in the CD25-depleted group, suggesting an in vivo induction or expansion of rare transferred donor Tregs. Thus, our study showed that removal of CD25+ Tregs enhanced anti-tumour immunity against local growth of a B cell lymphoma and that induction or expansion of Tregs could be one mechanism by which the growing tumour evades immune surveillance.
High mobility group box 1 and adenosine are both released by endothelial cells during hypothermic preservation
Authors: Song H , Feng Y , Hoeger S , Beck G , Hanusch C , Goettmann U , Leuvenink H G D , Ploeg R J , Hillebrands J , Yard B A 
Published: July 2010

Summary
Hypothermic preservation of solid allografts causes profound damage of vascular endothelial cells. This, in turn, might activate innate immunity. In the present study we employed an in vitro model to study to what extent supernatants of damaged endothelial cells are able to activate innate immunity and to study the nature of these signals. The expression of high mobility group box 1 (HMGB1) and adhesion molecules on human umbilical vein endothelial cell was studied by immunofluorescence, fluorescence activated cell sorter and Western blotting. Cytokine production was performed by enzyme-linked immunosorbent assay. HMGB1 expression was lost completely in endothelial cells after hypothermic preservation. This was associated with cell damage as it occurred only in untreated endothelial cell but not in cells rendered resistant to hypothermia-mediated damage by dopamine treatment. Only supernatants from hypothermia susceptible cells up-regulated the expression of interleukin (IL)-8 and adhesion molecules in cultured endothelial cells in an HMGB1-dependent manner. In whole blood assays, both supernatants of hypothermia susceptible and resistant cells inhibited tumour necrosis factor (TNF)-α production concomitantly with an increased IL-10 secretion. The activity of the supernatants was already found after 6 h of hypothermic preservation, and paralleled the decrease in intracellular adenosine triphosphate (ATP) levels. Modulation of TNF-α and IL-10 production by these supernatants was abrogated completely by prior treatment with adenosine deaminase and was similar to the response of an A2R agonist. Our study demonstrates that both HMGB1 and adenosine are released during hypothermic preservation. While release of HMGB1 is caused by cell damage, release of adenosine seems to be related to ATP hydrolysis, occurring in both susceptible and resistant cells.
Up-regulated expression of Toll-like receptors mRNAs in peripheral blood mononuclear cells from patients with systemic lupus erythematosus
Authors: Komatsuda A , Wakui H , Iwamoto K , Ozawa M , Togashi M , Masai R , Maki N , Hatakeyama T , Sawada K 
Published: July 2010

Summary
Recent studies in animal models for systemic lupus erythematosus (SLE) have shown that Toll-like receptors (TLR-7 and TLR-9) and interferon (IFN)-α are involved in the pathogenesis of murine lupus. Recent studies using flow cytometry have also shown increased expression of TLR-9 in peripheral blood mononuclear cells (PBMCs) from SLE patients. In this study, we performed quantitative real-time reverse transcription–polymerase chain reaction analyses of PBMCs from 21 SLE patients and 21 healthy subjects, to estimate TLR2, TLR3, TLR4, TLR5, TLR7, TLR8, TLR9, IFN-α and LY6E (a type I IFN-inducible gene) mRNA expression levels. Expression levels of TLR2, TLR7, TLR9, IFN-α and LY6E mRNAs in SLE patients were significantly higher than those in healthy controls. Expression levels of TLR7 and TLR9 mRNAs correlated with that of IFN-α mRNA in SLE patients. These results suggest that up-regulated expression of TLR7 and TLR9 mRNAs together with increased expression of IFN-α mRNA in PBMCs may also contribute to the pathogenesis of human lupus.
The role of a nuclear protein, histone H1, on signalling pathways for the maturation of dendritic cells
Authors: Hsu L W , Chen C L , Nakano T , Lai C Y , Chiang K C , Lin Y C , Kao Y H , Chen S H , Goto T , Sung W C , Yang C H , Cheng Y F , Jawan B , Chiu K W , Goto S 
Published: July 2010

SummaryWe have demonstrated previously that liver allograft tolerance is associated with the immunosuppressive activity of anti-histone H1 autoreactive antibodies induced in the serum of liver transplantation. Furthermore, we and others have shown that nuclear proteins such as histone H1 and high mobility group box 1 play an important role in maturation of dendritic cells (DCs), although the precise mechanisms are still unknown. In the present study, we focus upon the significance of histone H1 on DCs in terms of the intracellular signalling pathway of DCs. Our immunostaining and immunoblot studies demonstrated that histone H1 was detected in cytoplasm and culture supernatants upon the activation of DCs. Histone H1 blockage by anti-histone H1 antibody down-regulated the intracellular activation of mitogen-activated protein kinases (MAPKs) (p38) and IκBα of DCs, and inhibited DC activity in the proliferation of CD4+ T cells. On the other hand, the addition of histone H1 without endotoxin stimulation up-regulated major histocompatibility complex class II, the CD80 and CD86 surface markers of DCs and the activation of MAPKs (p38 and extracellular-regulated kinase 1/2) and IκBα. These results suggest that the translocation of histone H1 from nuclei to cytoplasm and the release of their own histone H1 are necessary for the maturation of DCs and the activation for T lymphocytes.
Interleukin 12B gene polymorphism and apparent resistance to hepatitis C virus infection
Authors: Hegazy D , Thurairajah P , Metzner M , Houldsworth A , Shaw S , Kaminski E , Demaine A G , Cramp M E 
Published: July 2010

Summary
Cellular immunity with interferon gamma production could have a role in protection from hepatitis C virus (HCV). Interleukin (IL)-12 is a key cytokine in promoting such anti-viral T helper 1 (Th1) responses. We hypothesized that a genetic background able to promote cellular responses may be associated with apparent protection from infection and have investigated the distribution of the functional 1188A/C polymorphism of IL-12B in HCV exposed but uninfected cases. The frequency of the high IL-12-producing C allele was determined by restriction enzyme genotyping in 76 exposed–uninfected individuals and 105 healthy controls. Overall, the C allele was found in 27·6% of exposed–uninfected cases compared with 16·7% of healthy controls [χ2 = 6·3, P = 0·02, odds ratio (OR) = 1·9, 95% confidence interval (CI) = 1·1–3·2]. CC genotype was found in 10·5% of exposed–uninfected cases compared with 0·9% controls (χ2 = 9·3, P = 0·01, OR = 12, 95% CI = 1·5–100). Individuals at high risk of HCV infection yet who remain uninfected may be resistant in some way to infection. In our cohort of exposed–uninfected cases a genetic background of enhanced IL-12 production was associated with apparent resistance to HCV infection. This lends support to a central role for cellular immune responses in protecting from infection.
Ageing is associated with diminished apoptotic cell clearancein vivo
Authors: Aprahamian T , Takemura Y , Goukassian D , Walsh K 
Published: July 2010

SummaryAgeing leads to immune system dysfunction and the accumulation of autoantibodies. Because the rapid phagocytic clearance of apoptotic cells is required to prevent the development of autoimmunity, we examined the relative clearance of apoptotic material in young and aged mice using two independent assays. First, 2-year-old mice were found to be impaired in their ability to clear apoptotic keratinocytes following ultraviolet irradiation of the skin. Secondly, peritoneal macrophages exposed to apoptotic Jurkat T cells in vivo displayed diminished phagocytic activity in aged mice compared with 8-week-old mice. Consistent with these findings, aged mice exhibited signs of autoimmunity with the appearance of anti-nuclear antibodies and increased kidney glomerular size as well as complement deposits within the glomeruli. In vitro assays revealed that the pretreatment of macrophages with the serum from aged mice led to a reduction in their ability to phagocytose apoptotic bodies compared with macrophages treated with serum from young mice. These data show that the ageing process is accompanied by a diminished ability to clear apoptotic debris. This accumulation of apoptotic debris could contribute to immune system dysfunction that occurs in aged organisms.