bluuebunny/crossref_metadata_2025_split huggingface dataset:
Failure in antigen responses by T ceils from patients with common variable immunodeficiency (CVID)
Authors: STAGG A J , FUNAUCHI M , KNIGHT S C , WEBSTER A D B , FARRANT J 
Published: July 2010

SUMMARYAntigen-driven responses by T cells from patients with CVID and normal subjects have been assessed. Low-density cells enriched for antigen-presenting dendritic cells were cultured with T cells using a 20-μl hanging drop system, T cells from all subgroups of CVID patients showed markedly reduced responses lo the recall antigens purified protein derivative (PPD) or tetanus toxoid. whereas responses by cells from patients with X-linked agammaglobulinaemia, used as a disease control, were in the normal range. However, primary allo-stimulation of CVID T cells was normal, CVID cells from two patients failed lo respond to stimulation with a neoantigen, an HIV env peptide. under conditions where normal T ceils did respond. These data illustrate a profound defect in antigen-stimulated T cell proliferation in vitro in all groups of CVID patients, but do not distinguish whether the defect is in the presenting cell or in the T lymphocyte. In vitro, germinal centre B cells are thought lo present antigen to primed T cells lo obtain essential signals (e.g. CD40 ligand and IL-2) for B cell survival and progression to immunoglobulin secretion. A failure of antigen-specific T cell function in vivo in CVID would thus not provide the primed T cells needed for B cell rescue, and could be the primary defect leading to the low immunoglobulin production in this condition.
Qualitative and quantitative analyses of the antibody response elicited byHaemophilus influenzaetype b capsular polysaccharide–tetanus toxoid conjugates in adults with IgG subclass deficiencies and frequent infections
Authors: AVANZINI M A , BJÖRKANDER J , SÖDERSTRÖM R , SÖDERSTRÖM T , SCHNEERSON R , ROBBINS J B , HANSON L A 
Published: July 2010

SUMMARYTwenty-one IgG subclass-deficient adult patients with repeated infections of the respiratory tract, were immunized with Haemophilus influenzae type b capsular polysaccharide (HibCP) covalently bound to tetanus toxoid (TT). Specific immunoglobulin and IgG subclasses to HibCP and TT were quantified; the biological activities of HibCP antibodies were also investigated. Most patients showed an antibody response similar to that observed in healthy adults, and the bactericidal activity related to the post-immunization levels of HibCP antibodies. No relation was found between immunoglobulin isotype deficiency, the clinical symptoms and the IgG subclass responsiveness, and no relation was observed between HibCP and TT antibody responses. Our data indicate that some, but not all, patients with recurrent infections and IgG subclass deficiency have an abnormal serum antibody response to polysaccharide and protein epitopes of Hib-TT conjugate vaccine. Analysis of the antibody response after vaccination with HibCP-TT conjugate vaccine did not seem to predict the clinical course of such patients.
Cellular and humoral immune responses to recombinant 65-kD antigen ofMycobacterium lepraein leprosy patients and healthy controls
Authors: ILANGUMARAN S , NARAYAN N P SHANKER , RAMU G , MUTHUKKARUPPAN V R 
Published: July 2010

SUMMARYCellular and humoral immune responses to recombinant 65-kD antigen of Mycobacterium leprae (rML65) were studied in leprosy patients and healthy contacts from a leprosy-endemic population. Peripheral blood mononuclear cells from a considerable proportion of tuberculoid leprosy patients, healthy contacts and non-contacts showed proliferative response to rML65 in vitro. A strong positive correlation was observed between the responses to rML65 and bacille Calmette-Guérin (BCG) or leprosin A. Addition of recombinant IL-2 (rIL-2) enhanced the proportion of responders to rML65 considerably in all groups of leprosy patients, healthy contacts and non-contacts. Among lepromatous patients this enhancement was more pronounced in the bacterial index (BI)-negative group. These results indicate that the 65-kD antigen of Myco. leprae is a dominant T cell immunogen in our study population. Though lepromatous patients showed poor lymphoproliferative response to rML65, their IgG antibody levels to the same antigen were markedly high. Most of the BI-positive lepromatous patients with elevated anti-rML65 IgG levels did not show T cell reactivity even with the addition of rIL-2. On the other hand, tuberculoid leprosy patients, healthy contacts and non-contacts showed good T cell reactivity but low levels of IgG antibodies to rML65, thus indicating the presence of an inverse relationship between cell-mediated and humoral immune responses to a defined protein antigen of Myco. leprae in humans. A significant proportion of individuals among tuberculoid leprosy patients, healthy contacts and non-contacts showed neither T cell reactivity nor elevated levels of IgG antibody to rML65. However, in most of these subjects, a T cell response to rML65 was demonstrable with the addition of rIL-2. These results are discussed with reference to the immunoregulatory mechanisms occurring during Myco. leprae infection on the basis of differential activation of Th1 and Th2 subsets.
Increase of both circulating Th1 and Th2 T lymphocyte subsets in IgA nephropathy
Authors: LAI K N , HO R T H , LAI C K W , CHAN C H S , LI P K T 
Published: July 2010

SUMMARYIgA nephropathy (IgAN), characterized by glomerular deposition of IgA and frequently elevated plasma IgA levels, has increased T helper cell activity. In vitro measurement of cytokines in supernatant of cultured peripheral lymphocytes revealed conflicting findings. We examined the profile of cytokine mRNA expressed in purified CD4+ cells in patients with IgAN in order to study their pattern of Th1 (releases IL-2 and interferon-gamma (IFN-γ)) and Th2 (releases IL-4 and IL-5) T cell response. We assessed the circulating CD4+ T cells in patients and normal controls by the expression of messenger RNA (mRNA) for IL-2, IL-4, IL-5 and IFN-γ. The cytokine mRNAs were analysed with reverse transcription-polymerase chain reaction and were measured semiquantitatively by using a housekeeping gene, β-actin. Compared with the control subjects, CD4+ T lymphocytes from patients with IgAN expressed a higher level of IL-2 mRNA (P=0·007), IFN-γ mRNA (P = 0·04), IL-4 mRNA (P = 0·048), and IL-5 mRNA (P=0·016). Within these patients with IgAN, a good correlation was demonstrated between the gene expression of cytokines in Th1 or Th2 cells. The IL-2 mRNA levels in Th1 cells from these patients with IgAN also correlated significantly with the IL-4 or IL-5 mRNA levels in their Th2 cells. Our study revealed IgAN is associated with activation in circulating lymphocytes of the IL-2, IFN-γ, IL-4 and IL-5 gene cluster, a pattern compatible with activation of both the Th1- and Th2-like T lymphocyte population. The increased transcription of these cytokine genes may be contributory to the immunopathologic findings in IgAN.
Absence of autoantibodies against glutamate decarboxylase (GAD) in the non-obese diabetic (NOD) mouse and low expression of the enzyme in mouse islets
Authors: VELLOSO L A , EIZIRIK D L , KARLSSON F A , KÄMPE O 
Published: July 2010

SUMMARYGAD is a major islet cell autoantigen in human type 1 diabetes mellitus. Autoantibodies are preferentially directed against the 65-kD isoform of the enzyme which is the only form expressed in human islets of Langerhans. The NOD mouse is a spontaneous model of type I diabetes, frequently employed in studies dealing with the immunopathogenesis of the disease. In the present study the reactivity of sera from 34 prediabetic and 15 diabetic NOD mice was tested against GAD protein present in islets of Langerhans and cerebellum, and against recombinant., semi-purified GAD-65 and GAD-67. A rabbit antiserum (K2) raised against GAD-67 could readily recognize the recombinant GAD-67 and the isoform present in rat and mouse islets and mouse brain. A MoAb (GAD-6) specific for the GAD-65 isoform reacted against the recombinant GAD-65 and the isoform present in rat islets and mouse brain, whereas no reactivity was observed when using mouse islets. However, when testing the NOD mice sera by immunohistochemistry, immunoprecipitation and Western blot, no reactivity against any of the isoforms of GAD could be detected. Using reverse transcription polymerase chain reaction (PCR), GAD-67 mRNA could be detected in mouse and rat islets and in mouse brain. GAD-65 mRNA could also be detected in rat islets and mouse brain, but apparently a much lower copy number is present in mouse islets. These findings stress important diabetes in the immune response occurring in the animal model NOD mouse compared with human type 1 diabetes, and emphasize that human and animal type 1 diabetes possibly represent the final outcome of several different etiological factors.
Differential effect of glucocorticoids on tumour necrosis factor production in mice: up-regulation by early pretreatment with dexamethasone
Authors: FANTUZZI G , DEMURI M T , GHEZZI P 
Published: July 2010

SUMMARYGlucocorticoids (GC) are well known inhibitors of tumour necrosis factor (TNF) production. We investigated the role of endogenous GC in the regulation of TNF production in mice treated with lipopolysaccharide (LPS) using a pretreatment with dexamethasone (DEX) to down-regulate the hypothalamus-pituitary adrenal axis (H PA). Short-term DEX pretreatment (up to 12 h before LPS) inhibited TNF production, but earlier (24–48 h) pretreatments potentiated it. This up-regulating effect was not observed in adrenalectomized mice or when GC synthesis was inhibited with cyanoketone (CK). This effect could not be explained only by the suppression of L PS-induced corticosterone (CS) levels induced by DEX, since a 48-h pretreatment potentiated TNF production without affecting LPS-induced CS levels. On the other hand, mice chronically pretreated with DEX were still responsive to its inhibitory effect on TNF production, thus ruling out the possibility of a decreased responsiveness to GC.
Intestinal B cell defects in common variable immunodeficiency
Authors: HERBST E W , ARMBRUSTER M , RUMP J-A , BUSCHER H-P , PETER H-H 
Published: July 2010

SUMMARYThe humoral immune system of the small intestine of 17 patients with common variable immunodeficiency (CVID) was studied by immunohistology using antibodies specific for IgA1,2, IgM, IgG1-4, the J chain and the secretory component (SC). IgA1,2+, IgG2+ and IgM+ lamina propria B cells were totally lacking in 65% (11/17), 41% (7/17) and 18% (3/17) of CVID patients, respectively. One patient exhibited an isolated IgA1 subclass deficiency. The proportion of plasma cells in conventionally stained histological sections of the same intestinal biopsies showed a close correlation with the numbers of IgA+ and IgM+ cells. Considerable numbers of J chain-synthesizing cells were present in all patients with CVID, indicating the presence of early B cells unable to differentiate into immunoglobulin-producing plasma cells. Most of the patients with intestinal IgA and/or IgM defects strongly expressed the SC in their enterocytes, suggesting an immunoglobulin-independent regulation of the SC. Clinically, only CVID patients with intestinal IgA defects developed intestinal infections with Giardia lambtia, Campylobacter jejuni or Candida albicans. The outcome of in vitro immunoglobulin synthesis assays with peripheral blood lymphocytes did not predict the presence or absence of the respective isotype-producing B cells in the intestinal lamina propria. Thus, immunohistological examinations of intestinal biopsies are required to determine the extent of mucosal immunodeficiency in CVID patients.
Processing and presentation of tetanus toxin by antigen-presenting cells from patients with chronic granulomatous disease (CGD) to human specific T cell clones are not impaired
Authors: BARBEY C , TIERCY J M , FAIRWEATHER N , NIEMANN H , SEGER R , CORRADIN G 
Published: July 2010

SUMMARYThe capacity of peripheral blood lymphocytes (PBL) or Epstein-Barr virus (EBV)-transformed B cell lines from CGD patients to process and present tetanus toxin (tt)-specific epitopes was assessed using various tt preparations and human tt-specific T cell clones. PBL from all of the donors were able to process and present either native tt and/or denatured tt to human T cell clones specific for various tt epitopes. Furthermore, no difference was found in the antigen requirement when normal or CGD EBV-B cell lines were used as antigen-presenting cells (APC). These results suggest that the deficiency in oxygen metabolism in CGD cells does not affect tt processing and presentation.
Activated neutrophils express proteinase 3 on their plasma membrane in vitro and in vivo
Authors: CSERNOK E , ERNST M , SCHMITT W , BAINTON D F , GROSS W L 
Published: July 2010

SUMMARY
Apart from the diagnostic value of anti-neutrophil cytoplasmic antibodies (ANCA), their detailed characterisation and that of their corresponding antigens have opened new ways for the exploration of the pathogenesis of primary systemic vasculitis. ANCA arc now thought to play an important functional role via activation of phagocytic cells (e.g. polymorphonuclear neutrophils (PMN)). In this study we examined the mechanisms by which ANCA could gain access to proteinase 3 (PR3) in intact PMN, at two levels: ex vivo by analysing the presence of PR3 on the plasma membrane of PMN from patients with ANCA-associated vasculitis, and in vitro by stimulation of PMN using different cytokines, including recombinant tumour necrosis factor-alpha (rhTNF-α) and two forms of IL-8 (produced by monocytic and endothelial cells). Using immunocytochemical staining techniques (FACS and immunoelectronmicroscopy) PR3 has been detected on the plasma membrane of PMN from patients with active ANCA-associated vasculitis. However, this phenomenon is also seen in patients with sepsis who do not have ANCA. In addition. TNF-α and both forms of IL-8 act synergistically and induce a translocation of PR3 from the intragranular loci to the cell surface of PMN. These results provide strong evidence for the hypothesis that ANCA are directly pathogenic by binding to PR3 which is expressed on the cell surface of primed/activated PMN.
Anti-proteinase 3 antibodies, their characterization and disease associations
Authors: JENNINGS J G , CHANG L , SAVIGE J A 
Published: July 2010

SUMMARY
Anti-proteinase 3 antibodies are a subgroup of anti-neutrophil cytoplasmic antibodies (ANCA), and we have established an ELISA for their detection using high performance liquid chromatograhy (HPLC)-purified protein. This assay is sensitive and specific: inhibition studies have shown that despite the homology between proteinase 3 and elastase there is no cross-reactivity between the corresponding antibodies for their targets. Anti-proteinase 3 antibodies were associated most often with cytoplasmic fluorescence (17/22, 77%), but occasionally with a perinuclear (3/22, 14%) or atypical pattern (1/2). These antibodies were found in 23 out of 76 sera (30%) that were positive in an ELISA based on a crude neutrophil cytoplasmic extract, and they were associated with both 29 and 55 kD bands on Western blots. Anti-proteinase 3 antibodies were found in most individuals with active Wegener's granulomatosis (10/13, 77%). but less often in individuals with microscopic polyarteritis (2/10, 20%) or segmental necrotizing glomerulonephritis (3/6, 50%). However, anti-proteinase 3 antibodies were not detected in any of 32 sera from individuals with rheumatoid arthritis or systemic lupus erythematosus (SLE). Occasionally anti-proteinase 3 antibodies were associated with anti-glomerular basement membrane antibodies (1/11, 9%) or with anti-mycloperoxidase antibodies(1/11.9%), IgM anti-proteinase 3 antibodies were uncommon (2/22 sera, 9%), and no IgA antibodies were demonstrated in any of 22 sera from patients with active systemic vasculitis. Significantly more individuals presented with anti-proteinase 3 antibodies in April-May-June, suggesting that an infective agent prevalent in Autumn might have a causative role in the associated diseases. Anti-proteinase 3 antibodies are the most common target antigen associated with Wegener's granulomatosis and cytoplasmic fluorescence.
Inhibition of CD4+ T lymphocyte binding to fibronectin and immune-cell accumulation in inflammatory sites by non-peptidic mimetics of Arg-Gly-Asp
Authors: HFRSHKOVIZ R , GREENSPOON N , MFKORI Y A , HADARI R , ALON R , KAPUSTINA G , LIDER O 
Published: July 2010

SUMMARY
The Arg-Gly-Asp (RGD) cell adhesion motif has been demonstrated in various studies to play a pivotal rote in leucocyte and platelet interactions with plasma and extracellular matrix (ECM) glycoproteins. The recognition the RGD sequence is mediated by heterodimeric receptors designated integrins of the β1 subfamily, expressed on distinct cell types, including T lymphocytes. We have recently shown that flexible non-peptidie mimetics of RGD, in which the two ionic side groups were separated by a linear spacer of 11 atoms, bound specifically to the platelet integrin α11bβ3, and inhibited T cell-mediated immune responses. The present study was designed to (i) further characterize the structural requirements for RGD interactions with CD4+T cells, and (ii) examine the mechanisms by which the RGD mimetics interfere with immune cell reactivity in vivo. We now report that freezing the conformational degrees of freedom in the spacer chain, which fixes the relative orientation of the guanidinium and carboxylate side groups in a favourable manner, resutls in a higher level of inhibition of T cell binding to immobilized fibronectin, an RGD-containing ECM glycoprotein. In vitro, treatment of mice with relatively low doses of the RGD mimetics, but not the RGD peptide, inhibited the elicitation of an adoptively transferred DTH reaction. This inhibition was achieved by direct impairment the ability of antigen-primed lymph node cells to migrate and accumulate in inflammatory sites. Hence, we suggest that the design and production of non-peptidic mimetics of RGD offers a novel approach to study defined parameters related to the structure-function requirements of small adhesion epitopes. Furthermore, this approach could be used therapeutically to inhibit pathological processes which depend on RCJD recognition.
High serum levels of soluble CD8 in insulin-dependent diabetes
Authors: DI CESARE E , PREVITI M , INGEMI M C , BAGNATO G F , CUCINOTTA D 
Published: July 2010

SUMMARYIn type I (insulin-dependent) diabetes mellitus (IDDM) CDS+ T cells represent the majority of lymphocytes which infiltrate the pancreatic islets during β cell destruction. Soluble CDS antigen (sCD8) has been shown to correlate with CD8 cell subset activation. In this study we measured by ELISA sCD8 levels in sera from: 33 newly diagnosed IDDM patients; 29 type 1 diabetics with duration of disease more than 1 year; 37 healthy siblings of IDDM patients; 19 healthy controls. Sera from both groups of IDDM patients and from healthy siblings exhibited soluble CDS mean levels significantly higher than controls (P=0·0001, P&lt;0·003, P&lt;0·03 respectively). Soluble CD8 levels above the normal range (mean±2 s.d. of controls) were found in a percentage of newly diagnosed subjects (54·5%) significantly higher than in subjects with a long-standing duration of disease (6·9%, P&lt;0·0005) and healthy siblings (16·2%, P0·002). Our results suggest that the raised levels of soluble CD8 near lo diabetes onset may indicate the activation of CD8+ T cells probably responsible for the autoimmune β cell destruction.
Occurrence of C3 nephritic factor and C4 nephritic factor in membranoproliferative glomerulonephritis (MPGN)
Authors: OHI H , YASUGI T 
Published: July 2010

SUMMARYOne hundred patents diagnosed with hypocomplementaemic MPGN (C3&lt;40%) were studied to determine the presence of C3 nephritic factor (C3NeF) and/or C4 nephritic factor(C4NcF). Of those studied, 12 were C3NeF-positivc, nine were C4NeF-positive and 10 were positive for both C3NeF and C4NeF. In the 10 patients both C3NeF- and C4NeF-posiiive, a marked decrease in C3 and C5 levels and a decrease in levels of laic components from C6 to C9 were observed. This observation was in contrast to that seen in patients who were either C 3NeF- or C4NeF-pusitive. Patients positive for both C3NeF and C4NeF continued to exhibit hypocomplementaemia after therapy. Immunofluorescent findings revealed heavy C3 immunoglobulin deposits in the 10 patients who were both C3NcF and C4NeF-positive, whereas no such deposits were found in those patients who were either C3 NeF or C4NeF-positive only. When those patients who were both C3NeF- and C4NeF-positive were compared with those who were either C3NeF- or C4NeF-positive, nephritic syndrome and a poor prognosis were observed more frequently. This study demonstrates a correlation between clinical outcome and hypocomplementaemic MPGN. Further investigations of MPGN as an autoimmune disease are necessary.
Proteinuria induced by anti-dipeptidyl peptidase IV (gp108); role of circulating and glomerular antigen
Authors: NATORI Y , SHINDO N , NATORI Y 
Published: July 2010

SUMMARYMassive proteinuria is induced in rats by administration of rabbit antibody to dipeptidyl peptidase IV (DPPIV, gp108), a glycoprotein present on glumerular cell membranes and in serum. This study was undertaken to know which antigen, glomerular or serum DPPIV, is responsible for forming immune complex in glomeruli and development of proteinuria. An i.p. injection of the antibody resulted in a rapid decrease of serum DPPIV and a gradual increase of rabbit IgG deposited along glomerular capillary wall for 4–8 h. Abnormal proteinuria appeared within 8 h, peaked on day 2 (&gt;200mg/24h) and then declined. An increase of urinary protein and glomerular deposition of IgG also occurred, when the antibody was injected into serum DPPIV-depleted rats that had received preinjection of anti-DPPIV antibody. These results suggest that proteinuria is induced by direct binding of anti- DPPIV antibody to the membrane antigen of glomerular cells.
IL-4 production is increased in cigarette smokers
Authors: BYRON K A , VARIGOS G A , WOOTTON A M 
Published: July 2010

SUMMARYCigarette smoking has been associated with both increases in serum levels of total IgE and an increased risk of developing allergic-like symptoms. IL-4 and interferon-gamma (IFN-γ) have reciprocal roles in the regulation of IgE synthesis, and as such prompted us to evaluate, in smokers, the production of these two cytokines. We demonstrate that phytohaemagglutinin (PHA)-induced IL-4 production by peripheral blood mononuclear cells (PBMC) of smokers (n= 19) is significantly higher than that of non-smokers (n=10, p &lt; 0·005). In addition, PBMC from heavy smokers, defined by the number of cigarettes smoked per day, produced significantly higher levels of IL-4 than those of light smokers. No difference between the groups was found for IFN-y production. Our data suggest an imbalance in cytokine production occurring in individuals who smoke. This imbalance, favouring IL-4 production, may be part of the mechanism responsible for the observed increases in serum IgE and allergic-like symptoms associated with cigarette smoking.