bluuebunny/crossref_metadata_2025_split huggingface dataset:
Th1 cytokine pattern in sarcoidosis is expressed by bronchoalveolar CD4+ and CD8+ T cells
Authors: Prasse A , Georges C G , Biller H , Hamm H , Matthys H , Luttmann W , Virchow Jr J C 
Published: March 2003

SUMMARYThe pathogenesis of pulmonary sarcoidosis has been related to an increased production of Th1-like cytokines. However, cytokine expression in sarcoidosis has not been systematically studied at a single-cell level. We therefore investigated the expression of IL-2, IL-4, IL-13, tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) intracellularly in bronchoalveolar lavage (BAL) and peripheral blood CD3+ T lymphocytes from patients with pulmonary sarcoidosis (radiologic stage II–III, n = 8) and normal controls (n = 9) by flow cytometry. In contrast to IL-4 and IL-13, the percentage of T lymphocytes expressing intracellular IL-2 (49·3 ± 21·3% versus 14·5 ± 15·6%), IFN-γ (75·5 ± 14·9% versus 32·6 ± 18·7%) and TNF-α (68·3 ± 18·7% versus 36·8 ± 20·8%) was significantly higher in patients with sarcoidosis than in normal controls (each P &lt; 0·005). In contrast to BAL lymphocytes, expression of these cytokines in peripheral blood lymphocytes did not differ between patients with sarcoidosis and normal controls. Close correlations were observed between the percentages of BAL lymphocytes expressing intracellular IL-2, IFN-γ and TNF-α, but not for IL-4 or IL-13. Analysis of the expression of these cytokines in T lymphocyte subsets revealed IL-2, IFN-γ, and TNF-α in CD4+ as well as CD8+ T lymphocytes, suggesting a contribution of TC1 cells to the production of proinflammatory cytokines in sarcoidosis. We conclude that a Th1-like cytokine pattern can be observed in CD4+ as well as in CD8+ BAL T lymphocytes in patients with pulmonary sarcoidosis.
TheLeishmania infantumacidic ribosomal protein LiP2a induces a prominent humoral responsein vivoand stimulates cell proliferationin vitroand interferon-gamma (IFN-γ) production by murine splenocytes
Authors: Soto M , Alonso C , Requena J M 
Published: March 2003

SUMMARYThe acidic ribosomal proteins of the protozoan parasite Leishmania infantum have been described as prominent antigens during both human and canine visceral leishmaniasis. In this study we present data showing that the intraperitoneal administration in BALB/c mice of the Leishmania LiP2a protein, in the absence of any added adjuvants, elicited a strong humoral response as an indication that the protein is a potent immunogen. Despite the evolutionary conservation of the acidic ribosomal proteins, the antibody response was found to be specific for the Leishmania protein. Another remarkable finding was the observation that the LiP2a protein stimulates the in vitro proliferation of splenocytes from either LiP2a-immunized or naive BALB/c mice. Since similar proliferative indices were observed in T cell-enriched cultures, it is likely that the LiP2a stimulating activity is due mainly to T lymphocyte expansion. Also, the stimulatory effect was demonstrated to be antigen-specific, since the proliferation was abrogated by the presence of anti-LiP2a antibodies. Interestingly, the LiP2a protein stimulated the production of substantial amounts of IFN-γ in cultured splenocytes from LiP2a-immunized mice. Our data indicate therefore that the immunostimulatory properties shown by this antigen should be taken into account when developing therapeutic and prophylactic vaccines against leishmaniasis.
Identification of structural variations in the carboxyl terminus of Alzheimer's disease-associated βA4[1–42] amyloid using a monoclonal antibody
Authors: Jayasena U L H R , Gribble S K , Mckenzie A , Beyreuther K , Masters C L , Underwood J R 
Published: March 2003

SUMMARY
The accumulation of amyloid plaques and amyloid congophilic angiopathy (ACA) in the brains of affected individuals is one of the main pathological features of Alzheimer's disease. Within these deposits, the βA4 (Aß) polypeptide represents a major component with the C-terminal 39–43 amino acid variants being most abundant. Using a mouse IgG1 MoAb produced by hybridoma βA4[35–43]-95.2 3B9, which reacts with the epitope is defined by the amino acid residues βA438[GVV]40, this study has identified a unique conformation within the carboxyl terminus of human βA4[1–42]. Although the βA438[GVV]40 sequence is present within the C-termini of human βA4[1–40] and βA4[1–43] and the βA4-containing region of human APP, the βA4[35–43]-95.2 3B9 MoAb (designated MoAb 3B9) does not bind these polypeptides, demonstrating a high degree of specificity for the βA438[GVV]40 epitope as presented within the βA4[1–42] sequence. The βA4[1–42] epitope bound by MoAb 3B9 is sensitive to heating (100°C for 5 min) and is denatured by SDS but not by oxidative radio-iodination of βA4 or by adsorption to plastic surfaces or nitrocellulose. The recognition of βA4 plaque deposits and ACA by MoAb 3B9 within formalin-fixed sections of human AD brain demonstrates the potential of these antibodies for investigating the role of the unique βA4[1–42] conformation in the development of Alzheimer's disease.
Anti-CD3-induced and anti-Fas-induced apoptosis in systemic lupus erythematosus (SLE)
Authors: Bijl M , Horst G , Limburg P C , Kallenberg C G M 
Published: March 2003

SUMMARYDisturbances in apoptosis or in the clearance of apoptotic material might result in increased presentation of autoantigens which could be relevant to the pathogenesis of SLE. Data concerning defects in apoptosis in SLE are conflicting. To determine whether intrinsic defects in apoptosis induction occur in SLE irrespective of disease activity, we examined anti-CD3 and anti-Fas-induced apoptosis in vitro in SLE patients with inactive disease. Isolated peripheral blood lymphocytes (PBL) from 13 SLE patients and 14 healthy controls were incubated with anti-CD3, and, subsequently, after up-regulation of membrane Fas following anti-CD3 incubation, with anti-Fas. Expression of Fas and levels of apoptosis as detected by annexin V and propidium iodide staining were assessed by flow cytometry before and after the respective incubations. Fas expression on freshly isolated lymphocytes of SLE patients was increased whereas levels of circulating apoptotic cells were comparable between patients and controls. Stimulation with anti-CD3 resulted in up-regulation of membrane Fas in patients and in controls. In vitro induction of apoptosis by anti-CD3 as well as by anti-Fas occurred both in SLE patients and controls, and was higher in SLE patients after incubation with anti-CD3 as well as with anti-Fas. We conclude that Fas expression and in vitro induction of apoptosis are increased in SLE even in the absence of disease activity.
Monocyte-derived dendritic cells: a potential target for therapy inmultiple sclerosis (MS)
Authors: Duddy M E , Dickson G , Hawkins S A , Armstrong M A 
Published: March 2003

SUMMARYMonocytes can differentiate into dendritic cells (DC), cells with a pivotal role in both protective immunity and tolerance. Defects in the maturation or function of DC may be important in the development of autoimmune disease. We sought to establish if there were differences in the cytokine (granulocyte-macrophage colony-stimulating factor and IL-4)-driven maturation of monocytes to DC in patients with MS and whether drugs used to treat MS affected this process in vitro. We have demonstrated that there is no defect in the ability of magnetic activated cell sorting (MACS)-purified monocytes from patients with MS to differentiate to DC, but equally they show no tendency to acquire a DC phenotype without exogenous cytokines. Interferon-beta1a prevents the acquisition of a full DC phenotype as determined by light and electron microscopy and by flow cytometry. Methylprednisolone not only prevents the development of monocyte-derived DC but totally redirects monocyte differentiation towards a macrophage phenotype. Evidence is evolving for a role for DC in central nervous system immunity, either within the brain or in cervical lymph nodes. The demonstrated effect of both drugs on monocyte differentiation may represent an important site for immune therapy in MS.
Lack of evidence of a specific role for C4A gene deficiency in determining disease susceptibility among C4-deficient patients with systemic lupus erythematosus (SLE)
Authors: Dragon-Durey M-A , Rougier N , Clauvel J-P , Caillat-Zucman S , Remy P , Guillevin L , Liote F , Blouin J , Ariey F , Lambert B U , Kazatchkine M D , Weiss L 
Published: March 2003

SUMMARYThe aim of the present study was to investigate the prevalence of C4 and C2 deficiencies and to characterize genomic alterations in C4 genes in a large cohort of 125 unselected patients with SLE. We determined the protein concentration and functional activity of C2 and C4, as well as the C4 phenotype. C4 genotyping included Taq 1 restricted fragment lengh polymorphism (RFLP) analysis and polymerase chain reaction using sequence-specific primers (SSP-PCR). Type I C2 deficiency was diagnosed by PCR. Overall, 79·2% of the patients exhibited abnormalities of the C4 genes including deletion, non-expression, gene conversion and duplication. Among C4-deficient patients (n = 66, 52·8% prevalence), 41·0% of the patients exhibited a C4A deficiency and 59·0% a C4B deficiency. Half of the C4 deficiencies were due to a gene deletion. There was a strong association between C4A and C4B gene deletion and the presence of the DRB1*03 allele. Among the silent C4A genes, only two cases were related to a 2-bp insertion in exon 29 of the C4A gene. A gene conversion was demonstrated in eight patients (6·4%). One patient had a homozygous C4A deficiency. Three (2·4%) patients presented with a heterozygous type I C2 deficiency and none with homozygous deficiency. Our results argue against a specific role for C4A gene deficiency in determining disease susceptibility among patients with SLE that are C4-deficient.
Effect of deworming on human T cell responses to mycobacterial antigens in helminth-exposed individuals before and after bacille Calmette–Guérin (BCG) vaccination
Authors: Elias D , Wolday D , Akuffo H , Petros B , Bronner U , Britton S 
Published: March 2003

SUMMARY
The protective efficacy of BCG vaccination against pulmonary tuberculosis (TB) is highly variable in different populations. The reason remains to be elucidated. This study aims to investigate the possible effect of intestinal helminths on the immune response to PPD in naturally immunized or BCG-vaccinated humans. The study population was assessed for helminthic infection and those found to be positive were randomly assigned to either an albendazole treatment group or a control group who received a placebo. The immune response to PPD was compared between the two groups. In addition, subjects who were tuberculin skin test-negative in both groups were BCG vaccinated and later on tested for PPD-specific responses. Albendazole induced elimination/or reduction in intestinal worms resulting in a significant improvement in T cell proliferation and in interferon-gamma production by peripheral blood mononuclear cells (PBMC) stimulated with PPD. Moreover, BCG vaccination significantly improved PPD-specific immune responses in the treated group but not in the placebo group. The differences in the in vivo skin test responses were not significant. The data show that cellular immune responses to PPD are reduced in persons with concurrent helminthic infections, perhaps reflecting a lowered resistance to mycobacterial infections. This could explain, at least in part, the reduced efficacy of BCG against TB in helminth-endemic areas of the world.
Impaired degradation of serum amyloid A (SAA) protein by cytokine-stimulated monocytes
Authors: Migita K , Yamasaki S , Shibatomi K , Ida H , Kita M , Kawakami A , Eguchi K 
Published: March 2003

SummarySecondary amyloidosis (AA amyloidosis) is a systemic disease characterized by the extracellular tissue deposition of insoluble amyloid A (AA) protein. Aberrant metabolism of serum amyloid A (SAA) by macrophages is only one of many putative mechanisms which may be important in AA amyloidogenesis. In this study, we investigated the effects of cytokines on human monocyte-mediated SAA proteolysis. Human peripheral blood mononuclear cells (PBMC) or CD14+ monocytes were cultured with SAA, and the culture supernatants were then subjected to anti-SAA immunoblot. CD14+ monocytes degraded SAA completely. Whereas, when CD14+ monocytes were pretreated with IL-1β or IFN-γ, increasing amounts of SAA-related derivatives were detected in culture supernatants. These findings suggest that activation of monocytes by IL-1β or IFN-γ hampers the proteolysis of a precursor protein and leads to a partial degradation of SAA. This down-regulated proteolysis of SAA protein by cytokine-stimulated monocytes may play a role in the mechanism of AA amyloid formation as well as its removal.
Early immune responses accompanying human asymptomatic Ebola infections
Authors: Leroy E M , Baize S , Debre P , Lansoud-Soukate J , Mavoungou E 
Published: March 2003

SUMMARY
In a recent study we identified certain asymptomatic individuals infected by Ebola virus (EBOV) who mounted specific IgG and early and strong inflammatory responses. Here, we further characterized the primary immune response to EBOV during the course of asymptomatic infection in humans. Inflammatory responses occurred in temporal association with anti-inflammatory phase composed by soluble antagonist IL-1RA, circulating TNF receptors, IL-10 and cortisol. At the end of the inflammatory process, mRNA expression of T-cell cytokines (IL-2 and IL-4) and activation markers (CD28, CD40L and CTLA4) was up-regulated, strongly suggesting T-cell activation. This T-cell activation was followed by EBOV-specific IgG responses (mainly IgG3 ang IgG1), and by marked and sustained up-regulation of IFNγ, FasL and perforin mRNA expression, suggesting activation of cytotoxic cells. The terminal down-regulation of these latter markers coincided with the release of the apoptotic marker 41/7 NMP in blood and with the disappearance of viral RNA from PBMC, suggesting that infected cells are eliminated by cytotoxic mechanisms. Finally, RT-PCR analysis of TCR-Vβ repertoire usage showed that TCR-Vβ12 mRNA was never expressed during the infection. Taken together, these findings improve our understanding about immune response during human asymptomatic Ebola infection, and throw new light on protection against Ebola virus.
Melatonin provides signal 3 to unprimed CD4+ T cells but failed to stimulate LPS primed B cells
Authors: Raghavendra V , Singh V , Shaji A V , Vohra H , Kulkarni S K , Agrewala J N 
Published: March 2003

SUMMARYGrowing evidence has supported the conclusion that melatonin, a pineal hormone, modulates the immune function. In our previous study, we evaluated in vivo the potential role of melatonin in the regulation of the antigen specific T and B cells. In the present study, we observe that melatonin down-regulated the expression of the co-stimulatory molecule B7-1 but not B7-2 on macrophages. Further, melatonin encouraged the proliferation of anti-CD3 antibody activated CD4+ T cells only in the presence of antigen-presenting cells and promoted the production of Th2-like cytokines. Furthermore, it failed to influence the activity of B cells in a T-independent manner. Melatonin suppressed the release of TNF-α by LPS or IFN-γ activated macrophages but failed to inhibit nitric oxide (NO) release. Thus the study shows that melatonin can engineer the growth of unprimed CD4+ T cells if both the signals are provided by antigen-presenting cells. However, it could not regulate the function of B cells.
Lupus anticoagulant and history of thrombosis are not associated with persistent endothelial cell activation in systemic lupus erythematosus
Authors: Frijns C J M , Derksen R H W M , De Groot P H G , Algra A , Fijnheer R 
Published: March 2003

SummaryAntiphospholipid antibodies (aPL), especially lupus anticoagulant (LAC), characterize systemic lupus erythematosus (SLE) patients at increased risk for arterial and venous thromboembolic complications. It has been reported that purified human anti-phospholipid antibodies cause endothelial cell activation in in vitro experiments. In order to investigate whether increased endothelial cell activation is associated with thromboembolic events in SLE patients with LAC, we measured plasma levels of thrombomodulin (TM), von Willebrand factor (vWf), sP-selectin, vascular cell adhesion molecule-1 (sVCAM-1) and ED1-fibronectin in a study of 76 patients with SLE. Patients were subdivided on the basis of: no history of thrombosis and LAC-negative (n = 22) or LAC-positive (n = 17); positive history of thrombosis and LAC-negative (n = 16) or LAC-positive (n = 21). The median SLE disease activity index (SLEDAI) was 4. Although concentrations of sTM, vWf, sP-selectin and sVCAM-1 were significantly elevated in SLE compared with values in healthy controls, they did not differ between the four groups, between patients with or without history of thrombosis, and between patients with or without LAC. Presence of anticardiolipin antibodies could not explain these negative findings. Adjustment of the concentrations for significantly associated variables, such as age, hypertension, smoking, immunosuppressive treatment and concentrations of creatinine, cholesterol and homocysteine, did not change the main results of the study. Only sTM was significantly lower in patients with both LAC and thrombosis than in patients without both these features after adjustment for serum creatinine concentrations. In conclusion, we did not find an association between endothelial cell activation and presence of LAC or history of thrombosis in SLE.
Regulation of LPS induced IL-12 production by IFN-γand IL-4 through intracellular glutathione status in human alveolar macrophages
Authors: Dobashi K , Aihara M , Araki T , Shimizu Y , Utsugi M , Iizuka K , Murata Y , Hamuro J , Nakazawa T , Mori M 
Published: March 2003

SUMMARYInterleukin-12 (IL-12) is secreted from monocytes and macrophages; it exerts pleiotropic effects on T cells and natural killer (NK) cells, and stimulates interferon-γ (IFN-γ) secretion. Glutathione tripeptide regulates the intracellular redox status and other aspects of cell physiology. We examined whether IFN-γ and IL-4 affect the balance between intracellular reduced glutathione (GSH) and oxidized (GSSG) glutathione, as this may affect IL-12 production in human alveolar macrophages (AM). We used both AM from healthy non-smokers obtained by bronchoalveolar lavage and the monocytic THP-1 cell line in this study. Incubation of AM for 2 h with the GSH precursor N-acetylcysteine (NAC) increased the intracellular GSH/GSSG ratio, and enhanced lipopolysaccharide (LPS)-induced IL-12 secretion by AM. In THP-1 cells, NAC increased the GSH/GSSG ratio and the expression of LPS-induced IL-12 mRNA, whereas L-buthionine-[S,R]-sulphoximine (BSO) decreased these. NAC and BSO offset their own effects on the intracellular GSH/GSSG ratio and the expression of LPS-induced IL-12 mRNA. Furthermore, exposure of AM to the helper T cell type 1 (Th1) cytokine IFN-γ or the helper T cell type 2 (Th2) cytokine IL-4 for 72 h increased and decreased the GSH/GSSG ratio, respectively. Lipopolysaccharide (LPS)-induced secretion of IL-12 in AM was enhanced by IFN-γ but inhibited by IL-4. These results suggest that IFN-γ and IL-4 oppositely affect the GSH/GSSG balance, which may regulate IL-12 secretion from AM in response to LPS.
Identification of antigenic domains on the human sodium-iodide symporter which are recognized by autoantibodies from patients with autoimmune thyroid disease
Authors: Kemp E H , Waterman E A , Ajjan R A , Smith K A , Watson P F , Ludgate M E , Weetman A P 
Published: March 2003

SUMMARYThe sodium-iodide symporter (NIS) is a novel autoantigen in autoimmune thyroid disease. In the present study we have characterized the antigenic domains on the human symporter which are recognized by autoantibodies from patients with either Graves' disease (GD) or autoimmune hypothyroidism (AH). Deletion derivatives of complementary DNA (cDNA) encoding the Na+/I− symporter were constructed using polymerase chain reaction (PCR) amplification. These deletion constructs were translated in vitro with the concomitant incorporation of [35S]methionine into the protein products. The reactivity of seven GD and six AH sera, which were known to contain symporter-binding antibodies, to each of the radiolabelled modified symporters was then determined in immunoprecipitation experiments. Analyses of the results obtained in the radiobinding assays suggest the existence of multiple antibody binding sites on human NIS (hNIS), including regions between amino acids (aa) 1–134, 191–286, 290–411, 411–520 and 520–588. Computer prediction of the potential B cell epitopes on the symporter revealed that, apart from aa 134–191, all the epitope domains identified overlapped, at least in part, with areas predicted to be highly antigenic. Interestingly, the antigenic domains represented by aa 191–286, 290–411 and 411–520 include regions of the polypeptide which form putative extracellular domains in the secondary structure model of the rat symporter. No correlation between the recognition of specific epitopes on the human symporter and the type of autoimmune thyroid disease was demonstrated.
Heterogeneity of human Ro ribonucleoproteins (RNPS): nuclear retention of Ro RNPS containing the human hY5 RNA in human and mouse cells
Authors: Gendron M , Roberge D , Boire G 
Published: March 2003

SummaryRo ribonucleoproteins (RNPs) are autoantigens that result from the association of a 60-kDa protein (Ro60) with a small RNA (hY1, hY3, hY4 or hY5 in humans, mY1 or mY3 in mice). Previous studies localized Ro RNPs to the cytoplasm. Because Ro RNPs containing hY5 RNA (RohY5 RNPs) have unique biochemical and immunological properties, their intracellular localization was reassessed. Subcellular distribution of mouse and human Ro RNPs in intact and hY-RNA transfected cells was assessed by immunoprecipitation and Northern hybridization. Human RohY1−4 RNPs as well as murine RomY1, mY3 RNPs are exclusively cytoplasmic. Ro RNPs containing an intact hY5 RNA, but not those containing a mutated form of hY5 RNA, are found in the nuclear fractions of human and mouse cells. RohY5 RNPs are stably associated with transcriptionally active La protein and are known to associate with RoBPI, a nuclear autoantigen. Our results demonstrate that RohY5 RNPs are specifically present in the nucleus of cultured human and murine cells. The signal for nuclear localization of RohY5 RNPs appears to reside within the hY5 sequence itself. In conclusion, we suggest that the unique localization and interactions of primate-specific RohY5 RNPs reflect functions that are distinct from the predicted cytoplasmic function(s) of more conserved Ro RNPs.
Antiphosphatidylserine antibodies are elevated in normal tension glaucoma
Authors: Kremmer S , Kreuzfelder E , Klein R , Bontke N , Henneberg-Quester K B , Steuhl K P , Grosse-Wilde H 
Published: March 2003

SummaryThe two main entities of open-angle glaucoma are primary open-angle glaucoma (POAG) and normal tension glaucoma (NTG). Both diseases may be associated with autoimmune processes. Therefore, IgG and IgM antibodies to phospholipids (APL) and their subspecies cardiolipin (ACL), phosphatidylserine (APS) and β2-glycoprotein (β2GP) were determined in 43 NTG patients, 40 POAG patients and 40 healthy controls in a prospective study. The most prominent observation was the increase in APS concentrations in NTG patients (IgG 20·6 ± 2·7 U/ml, IgM 24·4 ± 3·4 U/ml) compared with POAG patients (IgG 8·8 ± 1·2 U/ml, IgM 11·0 ± 1·7), and controls (IgG 7·7 ± 1·3 U/ml, IgM 12·8 ± 1·5 U/ml). APS may be important due to their binding specificity to phosphatidylserine molecules which become accessible during apoptosis; this in turn may lead to local thrombosis.