bluuebunny/crossref_metadata_2025 huggingface dataset:
Induction of an anti-Fab, anti-DNA and anti-RNA polymerase I autoantibody response net work in rabbits immunized with SLE anti-DNA antibody
Authors: ROMBACH E , STETLER D A , BROWN J C
Published: July 2010

Systemic lupus erythematosus (SLE)-like anti-IgG Fab autoantibodies (autoAb) were induced in rabbits by immunization with either human, mouse or rabbit anti-DNA Ab. In direct-binding radioimmunoassay (RIA), affinity-purified anti-normal rabbit (NR) Fab autoAb cross-reacted with normal mouse (NM) Fab, ssDNA (but not dsDNA), poly(dA,dT), and RNA polymerase I (RPI). Affinity-purified anti-NM IgG Ab isolated from the same antisera cross-reacted with NR Fab, ssDNA and RPI. In inhibition RIA, soluble NR Fab inhibited anti-NR Fab binding to NR Fab and ssDNA, but enhanced binding to RPI. In contrast, ssDNA or RPI inhibitors had no effect upon autoAb binding to NR Fab. Anti-DNA, anti-RPI and anti-RPI 190 kD subunit autoAb, induced by immunization with lupus mouse anti-DNA Ab, also reacted with NM Fab, but were idiotypically specific for lupus mouse anti-DNA Fab. Further, rabbit anti-DNA and anti-RPI IgG autoAb, induced by immunization with rabbit anti-DNA IgG, were each idiotypically specific for homologous and autologous rabbit anti-ssDNA Fab. Together, these data provide evidence that anti-DNA, anti-RPI and anti-Fab autoAb are linked in a complex, multiple-specific and perhaps regulatory, immune response idiotype network in SLE.
Intercellular adhesion molecule-1 (ICAM-1) in Graves' disease: contrast betweenin vivoandin vitroresults
Authors: CIAMPOLILLO A , NAPOLITANO G , MIRAKIAN R , MIYASAKI A , GIORGINO R , BOTTAZZO G F
Published: July 2010

We have reassessed the possible role of the adhesion molecule ICAM-l in the pathogenesis of thyroid autoimmunity. In order to do that, we have investigated its expression in eight Graves' thyroids both in vivo (i.e. on cryostat sections and on cell suspensions), and in vitro (i.e. on cells cultured in monolayers for 3 days), and the results were compared with those obtained with similar preparations from four normal glands. On cryostat sections, the expression of ICAM-1, and for comparison that of HLA Class I and Class II molecules, was studied by immunofluorescence (IFL), but the former were also assessed by a distinct immunohistochemical technique. ICAM-1 was not detected in thyrocytes in vivo of both normal and Graves' glands, but solely in endothelial cells and antigen-presenting cells (APC). This selective reaction was confirmed by a four-layer technique using specific markers which identify endothelial cells and thyrocytes. HLA Class II molecules were confirmed to be inappropriately expressed in thyrocytes of Graves' glands, but there was no co-expression of these products and ICAM-1 in the same cells. In contrast, ICAM-1 appeared de novo in a proportion of Graves' and normal thyrocytes soon after the attachment and spreading of these cells in monolayer cultures (36–48 h). Graves' thyrocytes showed a quantitively higher degree of expression compared with that detected on normal thyroid cells (40–70%versus 12–20%). Under these experimental conditions, the four-layer staining with thyroid microsomal antibodies confirmed that thyrocytes were indeed the positive cells which expressed ICAM-l. Blocking experiments with cultured thyrocytes from two Graves' glands and MoAbs to tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) did not prevent the occurrence of ICAM-l expression. As a result of our study, we failed to demonstrate that Graves' thyrocytes express ICAM-1 in vivo. The unexpected ease of inducing ICAM-1 on thyroid cells under certain in vitro conditions remains intriguing. The phenomenon could be the simple consequence of a mechanical effect rather than exerted by specific biological processes. Further investigations are, therefore, needed to establish whether lCAM-1 is really involved in the pathogenesis of Graves' disease.
Natural and acquired resistance toLeishmania: cellular activation byLeishmania aethiopicaof mononuclear cells from unexposed individuals is through the stimulation of natural killer (NK) cells
Authors: AKUFFO H , MAASHO K , HOWE R
Published: July 2010

Cells from normal non-Leishmania-exposed individuals could respond in vitro by proliferation and interferon-gamma (IFN-γ) production to Leishmania aethiopica stimulation. The main cell type that appeared to be activated following such stimulation was CD3−, CD16+/56+. i.e. NK cells. Of the few CD3+ cells responding, an involvement of CD8+ cells was evident in the absence of activation of CD4+ cells in normal individuals, while a different feature was observed when patients' cells were investigated. Cells from patients with L. aethiopica infection did not show this NK response, but rather the CD4+ cells were the prominent responding cells. No evidence of the involvement of superantigens or cells utilizing the γδ T cell receptor (γδcells) in the response of unexposed individuals was noted.
Anticardiolipin antibodies in HIV infection: association with cerebral perfusion defects as detected by 99mTc-HMPAO SPECT
Authors: RUBBERT A , BOCK E , SCHWAB J , MARIENHAGEN J , NÜBLEIN H , WOLF F , KALDEN J R
Published: July 2010

Anticardiolipin antibodies (ACA) belong to a heterogeneous group of antibodies directed against negatively charged phospholipids. In patients with rheumatic disorders, their presence has been correlated to the occurrence of thromboembolic complications, thrombocytopenia, abortions and other disease manifestations. Several studies have revealed the detection of mostly high-titre ACA in a significant proportion of HIV-infected patients without any known clinical relationship. In our study, ACA were detected in 17/34 HIV-infected patients, and their presence was significantly associated with the detection of cerebral perfusion abnormalities by 99mTc-HMPAO SPECT. SPECT scans were classified as normal or as focal or diffuse defects in uptake. Most patients (13/16) with cerebral perfusion defects had elevated ACA titres in contrast to 4/18 patients with normal SPECT findings (P= 0·002). Focal uptake defects were always associated with the presence of ACA. No correlation to clinical features or other laboratory parameters was evident. Our results suggest a possible implication of autoimmune mechanisms in the pathogenesis of cerebral perfusion abnormalities detected by SPECT scanning in HIV-infected patients. However, further studies are needed to evaluate the clinical significance and to develop possible therapeutic consequences.
Tryptic peptides of human thyroglobulin: I. Immunoreactivity with murine monoclonal antibodies
Authors: SABOORI A M , BUREK C L , ROSE N R , BRESLER H S , TALOR M , KUPPERS R C
Published: July 2010

Human thyroglobulin (Tg) was treated with trypsin at different concentrations of trypsin/Tg for various incubation times at 37°C using non-reducing conditions. A ratio of trypsin to Tg of 1:100 (w/w) was optimal to release small peptides that were reactive to murine MoAbs to human Tg. Most peptides were released after only 1 h incubation with trypsin, but these peptides were further degraded at longer incubation times. However, a few small peptides. the largest of which with an apparent molecular weight (MWap) of 40kD, resisted tryptic digestion up to at least 12 h of incubation. These resistant peptides were further degraded by trypsin at 18–24 h of incubation. Tryptic peptides of Tg, released at I h and 4 h of incubation, were analysed for their immunoreactivity to 16 well characterized anti-Tg MoAbs by Western immunoblot. Patterns of peptide recognition of these MoAbs were generally unique. Eight MoAbs reacted with peptides of MWapof 10–25 kD and above. Four other MoAbs reacted with peptides of MWap of 25 43 kD and above, and the remaining four reacted with peptides of MWap >43kD. Nine of these MoAbs failed to recognize peptides after reduction, suggesting that the MoAbs bind conformation-dependent epitopes. The above information will promote the development of models relating the structure of Tg to the autoimmune process, and may provide an understanding of those regions of Tg responsible for the induction of autoimmune thyroiditis.
IgG subclass distribution of thyroglobulin antibodies in patients with thyroid disease
Authors: CATUREGLI P , KUPPERS R C , MARIOTTI S , BUREK C LVNNE , PINCHERA A , LADENSON P W , ROSE N R
Published: July 2010

The IgG subclass distribution of thyroglobulin antibodies (TgAb) has been studied in Hashimoto and Graves’ patients by several investigators with conflicting results, in part explainable by methodological problems. We have recently developed a quantitative ELISA to measure in absolute terms the serum concentration of TgAb subclasses. The aim of the present study was to apply this method in a large series of patients with autoimmune as well as, for the first time, non-autoimmune thyroid diseases. We examined 28 patients with Hashimoto's thyroiditis, 30 with Graves’ disease, 21 with thyroid carcinoma and 18 with non-toxic goitre, all selected for the presence of TgAbs. The results indicated that TgAbs in thyroid diseases were not restricted to any particular isotype, but comprised all four IgG subclasses. IgG1 was represented similarly in the four groups. The same was true for IgG3, even though its contribution to the total antibody content was very small. IgG4 was the dominant subclass in patients with Graves’ disease, thyroid carcinoma and non-toxic goitre, probably reflecting a prolonged antigenic challenge. In Hashimoto's thyroiditis IgG2 was dominant, possibly because T helper lymphocytes infiltrating the thyroid are typically Th1 type.
Expansion of CD3+CD4−CD8− T cell population expressing high levels of IL-5 in Omenn's syndrome
Authors: MELAMED I , COHEN A , ROIFMAN C M
Published: July 2010

Omenn's syndrome is a fatal, autosomal-recessive combined immune deficiency characterized by several erythematous exfoliative eruptions, lymphadenopathy, hepatosplenomegaly, and elevated eosinophil count. In some of these patients an expansion of CD3+CD4−CD8− double negative (DN) T cell population was observed. We show here that the DN population represents a clonal expansion of T cells which preferentially use Vβ14 in their T cell receptor complex. Using polymerase chain reaction, we show that patient's DN cells express spontaneously high levels of IL-5, thus possibly explaining the abundance of eosinophils in this disorder. The increase of IgE observed in patients with Omenn's syndrome is unlikely to be related to IL-4 production, as IL-4 levels in patient samples were low. However, patient's low expression of interferon-gamma (IFN-γ), which has been reported to inhibit IgE production, may explain the elevated levels of IgE in this patient. The results thus highlight the importance of the inhibitory effect of IFN-γ on regulation of IgE production.
Low antibody affinity restricted to the IgA isotype in IgA nephropathy
Authors: LAYWARD L , ALLEN A C , HATTERSLEY J M , HARPER S J , FEEHALLY J
Published: July 2010

Antibody affinity affects the handling and behaviour of immune complexes, and experimental studies have shown that animals which produce predominantly low-affinity antibody are prone to immune complex deposition resulting in glomerulonephritis. In order to investigate the potential role of antibody affinity in the pathogenesis of IgA nephropathy, affinity of both IgA and IgG antibody isotypes during secondary response to systemic immunization with tetanus toxoid was studied in 20 patients with IgA nephropathy. Patients with IgA nephropathy produced IgA antibodies of significantly lower affinity than controls (P < 0.001), whereas IgG antibody affinities were similar. Contrasting with controls, patients' IgA antibody affinity was inversely related to antibody concentration, with higher responders producing large amounts of low-affinity antibody. IgG antibody affinity increased with time, and maturation of IgG antibody affinity was similar in both controls and patients. IgA affinity in controls decreased with time, and this lack of IgA affinity maturation may explain the relative unimportance of IgA in normal systemic immunity. This temporal decrease in IgA affinity was not observed in patients with IgA nephropathy. The production of low-affinity IgA in IgA nephropathy may provide an explanation for the predominant deposition of IgA in this disease.
Soluble intercellular adhesion molecule-1 (sICAM-1) as a marker of disease relapse in idiopathic uveoretinitis
Authors: ZAMAN A G , EDELSTEN C , STANFORD M R , GRAHAM E M , ELLIS B A , DIRESKENELI H , D'CRUZ D P , HUGHES G R V , DUMONDE D C , WALLACE G R
Published: July 2010

This study reports the results of a point prevalence study of markers of endothelial dysfunction in the serum of patients with idiopathic uveoretinitis. sICAM-l, soluble endothelial leucocyte adhesion molecule (sELAM), anti-endothelial cell antibodies (AECA) and von Willebrand factor (vWF) levels were measured in 32 patients with isolated idiopathic uveoretinitis and seven with uveitis in association with systemic disease, using commercial and in-house ELISAs. Raised levels of AECA were found in 31% of patients with isolated uveitis, vWFin 28%, sELAM in 15.6% and sICAM-1 in 31%. Further analysis revealed that raised sICAM-1 levels were closely associated with recent relapse of disease (P=0.00003). Patients with accompanying systemic disease were found to have a similar prevalence of these serum abnormalities to those with isolated ocular disease. In conclusion, vascular endothelial dysfunction may contribute to pathogenesis in uveoretinitis, and in particular sICAM-1 may prove a marker of disease relapse in this condition.
Immunological diagnosis of childhood coeliac disease: comparison between antigliadin, antireticulin and antiendomysial antibodies
Authors: LERNER A , KUMAR V , IANCU T C
Published: July 2010

The immunological markers proposed to supplement intestinal biopsy for the diagnosis of coeliac disease are antigliadin, antireticulin and antiendomysial antibodies. These antibodies have been studied separately or compared as pairs, but no prospective comparison of all three antibodies in childhood coeliac disease exists. Thirty-four confirmed coeliacs were compared with nine non-coeliacs with pathological small intestines, and 32 children with a normal intestinal histology. Sera were examined for IgG- and IgA-antigliadin antibodies (AGA) by ELISA, and for IgA-antireticulin antibodies (ARA) and IgA endomysial antibodies (EMA) by indirect immunofluorescence. In active coeliac disease, IgA-EMA was the most sensitive (97%), while IgA-AGA the least sensitive antibody (52%). The specificity of IgA-AGA, IgG-AGA, IgA-ARA, IgA-EMA was 95%, 92%, 100% and 98%, respectively. Positive predicted values of ARA and EMA were comparable (97-100%), while EMA had the highest negative predicted value (98%). Compared with IgG-AGA, IgA-EMA titres better reflected variations in dietary gluten, and correlated best with intestinal pathology. Compared with AGA and ARA sensitivity, specificity and predictive values, EMA is the most reliable serological marker for the diagnosis of coeliac disease. It reflects dietary changes in gluten and correlates best with intestinal histopathology. Therefore, it should be considered the best of the three serological tests available for childhood coeliac disease.
Circulating intercellular adhesion molecule-1 (ICAM-1) in autoimmune liver disease and evidence for the production of ICAM-1 by cytokine-stimulated human hepatocytes
Authors: THOMSON A W , SATOH S , NÜSSLER A K , TAMURA K , WOO J , GAVALHR J , VAN THIEL D H
Published: July 2010

A circulating form of the membrane-bound ICAM-1 (CD54). a ligand for lymphocyte function-associated antigen-1 (LFA-I), has recently been identified in normal human scrum. In this study. scrum levels of soluble ICAM-1 (sICAM-1) were determined by sandwich ELISA both in normal healthy individuals of both sexes and in subjects with autoimmune liver diseases. Patients with primary biliary cirrhosis (PBC). primary sclerosing cholangitis and chronic active hepatitis (autoimnune) showed significant elevations in sICAM-1 compared with normal healthy subjects. The median level in PBC was approximately seven-fold above normal. Significant elevations in sICAM-1 were also detected, however, in patients with inactive alcoholic cirrhosis, suggesting that impaired liver clearance might at least in part account for the increased serum levels seen in patients with autoimmune liver disease. In patients with PBC. sICAM-I levels were related to summary assessment of disease severity (Child-Pugh classification) and correlated significantly with serum biochemical indices of liver function, including measures both of cholestasis and liver cell injury. In contrast, serum levels of E-selectin did not differ significantly from healthy controis. Although it has been suggested that peripheral blood mononuclear cells (PBMC) may be a source of sICAM-I. investigation of ICAM-I gene expression by reverse transcriptase polymerase chain reaction revealed similar basal levels of ICAM-1 message in PBMC of normal individuals and those with active PBC. This suggests that PBMC may not be a significant source of sICAM-1 in this disease. Similar increases in ICAM-I mRNA expression were found in cultured, concanavalin A (Con A)-stimulated lymphocytes of both PBC patients and controls. Significantly, stimulation of cultured, normal human hepatocytes with proinflammatory cytokines and endotoxin induced cell surface expression of ICAM-1 and the secretion/shedding of sICAM-1 into the hepatocyte culture medium. This new finding suggests that hepatocytes may bean important sourceofsICAM-1 in autoimmune and other chronic liver diseases. The possible role of sICAM-1 in inflammatory disorders remains to be determined.
Expression of high-affinity IL-4 receptors on human melanoma, ovarian and breast carcinoma cells
Authors: OBIRI N I , SIEGEL J P , VARRICCHIO F , PURI R K
Published: July 2010

It has previously been shown that murine sarcoma cells express high-affinity IL-4 receptors (1L-4R) which are internalized after binding to the ligand (Puri et al., Cancer Res 1991; 51:3011–7). We have also reported that human renal cell carcinoma cells express high-affinity IL-4R. and IL-4 inhibits tumour growth in vitro (Obiri et al, J Clin Invest 1993; 91:88). In this study we investigated the expression and function of IL-4R on other human solid tumours. Human melanoma, ovarian carcinoma and breast carcinoma cell lines were assessed for the cell surface expression of IL-4R by radio-ligand receptor binding and for IL-4R gene expression by Northern blot analysis. Primary cultures of mesothelioma and neurofibrosarcoma cells were similarly investigated. Human melanoma, ovarian carcinoma and breast carcinoma cell lines expressed IL-4R on their cell surface with a dissociation constant (Kd) of 140-549 pM. These tumour lines expressed a single 4 kb species of mRNA for IL-4R. Similarly, primary cultures of mesothelioma and neurofibrosarcoma cells were positive for the IL-4R mRNA by Northern blot analysis. Fresh, non-cultured mesothelioma and neurofibrosarcoma tumour sections were also positive for the presence of IL-4R as determined by immunohistochemistry of frozen sections using anti-IL-4R antibody. In order to study possible functions of IL-4R, we evaluated the effects of 11.-4 on cell growth and its effect on MHC antigen expression in the presence or absence of interferon-gamma (IFN-γ)- In tissue culture, IL-4 reduced the growth of tumour cell lines and primary cell cultures studied. IL-4 had very title effect on MHC class I antigen expression on ovarian, breast and melanoma cell lines; however. MHC class I (HLA-DR) expression was enhanced on melanoma and breast carcinoma cells. IL-4 also enhanced the IFN-γ-induced class II expression on melanoma and breast carcinoma cells. Taken together, our observations indicate that IL-4R are expressed on a variety of human solid tumours and these receptors may be functional. IL-4 alone and in combination with IFN-γ may play a role in host immune response against cancers.
Avidity of Aspergillus umbrosus IgG antibodies in farmer's lung disease
Authors: KAUKONEN K , SAVOLAINEN J , VIANDER M , TERHO E O
Published: July 2010

Farmer's lung disease (FL), the commonest form of allergic alveolitis caused by repeated inhalation of mouldy hay is associated with exposure lo the fungus Aspergillus umbrosus among Finnish farmers. The antigen-binding avidity of A. umbrosus-specific IgG antibodies was measured in 12 EL patients in acute phases of initial and recurrent attacks and during 1 year follow up as well as in 12 healthy farmers and five healthy urban controls. The farmers' groups were further divided into two subgroups: subjects with short exposure (< 7 years) and subjects with long exposure (> 25 years). During the first acute phase PL patients with long exposure exhibited a high avidity of A. umbrosus-specific IgG antibodies that remained high during t he 1 year follow up, although the A. umbrosus-specific IgG antibody titre decreased. A re-exposure to mouldy hay leading to a recurrence further enhanced the maturation of the antibody avidity, so that an even higher A. umvrosus-specific IgG avidity with a less significant increase of antibody titre occurred than during the first acute attack. Notably higher IgG antibody avidity was observed in FL patients with long exposure than in healthy farmers or in healthy controls.
MHC class I, MHC class II and intercellular adhesion molecule-1 (ICAM-1) expression in inflammatory myopathies
Authors: BARTOCCIONI E , GALLUCCI S , SCUDERI F , RICCI E , SERVIDEI S , BROCCOLINI A , TONALI P
Published: July 2010

We investigated the relationship between the MHC-I, MHC-II and intercellular adhesion molecule-1 (ICAM-1) expression on myofibres and the presence of inflammatory cells in muscle specimens of 18 patients with inflammatory myopathies (nine polymyositis, seven dermatomyositis, two inclusion body myositis). We observed MHC-I expression in muscle fibres, infiltrating mononuclear cells and endothelial cells in every specimen. In seven patients, some muscle fibres were MHC-II-positive for the DR antigen, while the DP and DQ antigens were absent. ICAM-1 expression, detected in seven patients, was found in clusters of myofibres, associated with a marked MHC-1 positivity and a widespread mononuclear infiltration. Most of the ICAM-1-positive fibres were regenerating fibres. Furthermore, some fibres expressed both ICAM-I and DR antigens near infiltrating cells. This finding could support the hypothesis that myofibres may themselves be the site of autosensitization.
Disturbed immunoregulatory properties of the neuropeptide substance P on lymphocyte proliferation in HIV infection
Authors: COVAS M J , PINTO L A , VICTORINO R M M
Published: July 2010

The neuropeptide substance P (SP) is known to increase cell-mediated immune responses in animal models and healthy subjects. Several studies have suggested an involvement of neuropeptides in the immunopathogenesis of some diseases. The study of the immunomodulatory effects of neuropeptides, namely SP. may represent a model for the analysis of Immunoregulatory defects in HIV infection at the level of the interaction between the immune and nervous systems, both of which are known to be affected by the virus. In the present study, we investigate the possibility of a disturbance in the immunomodulatory properties of SP in HIV infection by analysing the effects of SP (10−10 10−6) on the lymphocyte proliferative responses to concanavalin A (Con A) and phytohaemagglutinin (PHA) assessed by3H-thymidine incorporation in peripheral blood lymphocytes from 34 HIV-infected patients (16 asymptomtic (ASY) persistent generalized lymphadenopathy (PGL); 18 ARC/AIDS) and in 37 healthy subjects. In ASY/ PGL HIV-infected patients, SP 10−7M was identified as the concentration inducing the maximal increase in the lymphocyte responses to Con A and PHA, similarly to what was observed in healthy subjects. In ARC/AIDS patients, SP appeared to inhibit the mitogenic responses, particularly those induced by Con A. in contrast to the effects found either in healthy subjects or in ASY/PGL patients. These results suggest the existence of an alteration in the in vitro immunomodulatory properties of SP in ARC/AIDS patients compared with healthy subjects and ASY/PGL patients. In conclusion, the unexpected finding of an inhibitory effect of SP on lymphocyte proliferation from ARC/AIDS patients justifies further investigation of the neuropeptide-dependent immunoregulatory systems in HIV infection.
Antibody-dependent enhancement of HIV-1 infection in human term syncytiotrophoblast cells culturedin vitro
Authors: TÓTH F D , MOSBORG-PETERSEN P , KISS J , ABOAGYE-MATHIESEN G , ZDRAVKOVIC M , HAGER H , ARANYOSI J , LAMPÉ L , EBBESEN P
Published: July 2010

We examined if Fc receptor-mediated antibody-dependent enhancement (FcR-ADE) or complement-mediated antibody-dependent enhancement (C′-ADE) of virus infection can contribute to increasing replication of HIV-1 in human syncytiotrophoblast (ST) cells. Here we report that both FcR-ADE and C′-ADE may result in enhanced virus release from HIV-1-infected ST cells. We show that FcR-ADF of HIV-1 infection in ST cells is mediated by FcRIII and other FcR(s) belonging to undetermined Fc classes and does not require CD4 receptors, whereas C'-ADE uses both CD4 and CR2-like receptors. FcR-ADE: seems to be more efficient in enhancing HIV-I replication than C′-ADE. While FcR-ADE leads to increased internalization of HIV-1. C′-ADE does not result in enhanced endocytosis of the virus. In addition, antibodies mediating FcR-ADE arc reactive with the gp120 viral envelope antigen, whereas antibodies involved in C′-ADE react with the viral transmembrane glycoprotein gp41. Data suggest that both FcR-ADH and C′-ADE may contribute lo the spread of HIV-1 from mother to the fetus.
Adenovirus infection induces loss of HLA class I and CD3 antigens, but does not induce cell surface presentation of the La (SS-B) autoantigen
Authors: PEEK R , WESTPHAL J R , PRUIJN G J M , VAN DER KEMP A J W , VAN VENROOIJ W J
Published: July 2010

Antibodies to the RNA polymerase III transcription termination factor La arc frequently found in the serum of patients with various autoimmune diseases. The mechanisms by which autoimmune responses are evoked remain largely obscure, hut the presentation of autoantigens on the cell surface during stress conditions has been reported as a possible factor. In this study we analysed the effects of adenovirus infection on the binding of anti-La antibodies to the surface of several human cell lines and on the levels of the membrane-expressed glycoproteins HLA class I. CD44 and (hcCD3 complex. In addition, we studied the relative amount and the intracellular distribution of the La protein as well U its association with the major species of non-coding virus-associated (VAI) RNA. While immunofluorescence patterns revealed a redistribution and possibly cell surface expression of the L a protein during infection, this could not be confirmed by other techniques. In contrast, surface levels of HLA class I proteins and CD3 complex were severely affected. The data suggest that the subcellular distribution of the La protein is not detectably influenced by adenovirus infection.
Lymphokine-activated killer cell function of peripheral blood mononuclear cells, spleen cells and regional lymph node cells in gastric cancer patients
Authors: KARIMINE N , ARINAGA S , INOUE H , NANBARA S , UEO H , AKIYOSHI T
Published: July 2010

Lymphokine-activated killer (LAK) cells generated by culture of peripheral blood mononuclear cells (PBMC). spleen cells (SPC) and regional lymph node cells (LNC) with IL-2 for 4 days were examined for their functional capabilities m 29 patients with gastric carcinoma. The cytotoxic activity of LAK cells induced from LNC was significantly lower than that from either PBMC or SPC. although there was no difference between PBMC or SPC. The induction of mRNA of interferon-gamma (IFN-γ) or tumour necrosis factor-alpha (TNF-α) and the production of these cytokines in the non-adherent LAK cells from LNC were also significantly reduced compared with those from PBMC or SPC. Further, the LAK cells from LNC secreted significantly lower levels of these cytokines when stimulated with tumour target, Raji cells, although the production of these cytokines was markedly increased by stimulation with the targets in all three cell populations. Phenotypic analysis of each cell population revealed a decreased proportion of the cells mediating natural killer (NK) activity, including CD16+. CD56+, and CD57+ cells in LNC either before or after culture, although OKIal+ and CD25+ cells were uniformly increased in all ceil populations after culture. Changes in subpopulations of CD4+ and CD8+ cells in LNC were not apparently different from PBMC or SPC. These results indicated the differential reactivity of each lymphocyte population to IL-2 and the reduced LAK cell function of LNC compared with PBMC or SPC in patients with gastric carcinoma.
The effects ofin vivocyclosporin A administration on rat thymic dendritic cells
Authors: DAMOISEAUX J G M C , BEIJLEVELD L J J , VAN BREDA VRIESMAN P J C
Published: July 2010

Cyclosporin A (CsA) induces a graft-versus-host-like disease (GVHD) in lethally irradiated Lewis rats reconstituted with syngeneic bone marrow. The role of the thymus in the generation of disease has been unequivocally established. It has been suggested that the CsA-induced disappearance of thymic dendritic cells (DC) is responsible for the generation of the autoaggressive cells. In this study we quantify the loss of DC upon in vivo CsA administration in normal and bone marrow-reconstituted rats using an isolation technique. The phenotype of the DC is determined using MoAbs recognizing antigens which are expressed on thymic medullary DC. Furthermore, the functional aspects are assessed by determining the antigen presentation capacity. Short-term CsA exposure clearly affects the number of DC isolated from the thymus in a concentration-dependent manner. However, in all instances a substantial number of DC can be isolated from CsA-treated animals. These isolated DC exhibit an identical phenotype and function as DC isolated from control animals. Therefore, the partial deficiency of DC can not be held as essential for loss of tolerance.
Age-related increase in the fraction of CD27−CD4+ T cells and IL-4 production as a feature of CD4+ T cell differentiationin vivo
Authors: NIJHUIS E W P , REMARQUE E J , HINLOOPEN B , VAN DER POUW-KRAAN T , VAN LIER R A W , LIGTHART G J , NAGELKERKEN L
Published: July 2010

The influence of ageing on phenotype and function of CD4+ T cells was studied by comparing young (19-28 years of age) and aged (75 84 years of age) donors that were selected using the SENIEUR protocol to exclude underlying disease. An age-related increase was observed in the relative number of memory cells, not only on the basis of a decreased CO45RA and increased CD45RO expression, but also on the basis of a decrease in the fraction of CD27+CD4+ T cells. Our observation that the absolute number of CD45RO+ CD4+ T cells was increased, while absolute numbers of CD27-CD4+ T cells remained unchanged in aged donors, indicates that the latter subset does not merely reflect the size of the CD45RO+ CD4+ T cell pool. The increased fraction of memory cells in the aged was functionally reflected in an increased IL-4 production and T cell proliferation, when cells were activated with the combination of anli-CD2 and anti-CD28, whereas lL-2 production was comparable between both groups. No differences were observed with respect to proliferative T cell responses or IL-2 production using plate-bound anti-CD3 or phytohaemagglutinin (PHA). The observation that IL-4 production correlated with the fraction of memory cells in young donors but not in aged donors suggests different functional characteristics of this subset in aged donors.
A human monoclonal IgA autoantibody—185/12—behaves like an autoimmune antiphospholipid antibody
Authors: YRON I , SHOHAT L , LAHAV J , WITZ I P , FISCH B
Published: July 2010

A human monoclonal anticardiolipin autoantibody (ACA) of the IgA-k isotype, designated 185/ 12, is described. The antibody was prepared from peripheral B cells, obtained from a patient with a history of habitual abortion, by immortalization with Epstein Barr virus (EBV). The antibody displays a strong binding activity to cardiolipin and phosphatidyl i-serine. but not to phosphatidyicholine, phosphatidylinositol, ssDNA and dsDNA, It binds to cardiolipin in a concentration-related and saturable manner (Kd = 3·0 × 10−8 M). This reaction is dependent upon the presence of bovine serum, and is fully inhibited by cardiolipin vesicles. The 185/12 antibody exhibits different binding patterns to the solid-phase bound cardiolipin-serum complex and to its individual components (cardiolipin and bovine serum). The βmax of 185/12 binding to the complex (0·968 OD units) is higher than the sum of the βmax values calculated for each one of the complex components (0·352 + 0·179 = 0·531 OD units). Bovine serum as well as purified /Vglycoprotein I (β2-GPI) in suspension inhibit the binding of 185/12 to the complex. 185/12 binding capacity increases in direct relation to the rising concentration of/β2 -GPL Collectively, these data may be interpreted to suggest that 185/12 antibody, which is an IgA isotype. exhibits characteristics usually attributed only to antiphospholipid autoantibodies (APA) of the IgG isotype. that are associated with the clinical spectrum of APA syndrome (APA-S). It is, therefore, possible that autoantibodies of the IgA isotype could play a pathogenic role, which may be different from that of the IgG isotype. in the development of autoimmune phenomena.
CD4+ T cells from collagen-induced arthritic mice are essential to transfer arthritis into severe combined immunodeficient mice
Authors: KADOWAKI K M , MATSUNO H , TSUJI H , TUNRU I
Published: July 2010

The role of T lymphocytes in the adoptive transfer of collagen-induced arthritis (CIA) in DBA/IJ mice to severe combined immunodeficient (SCID) mice was investigated. Spleen cells from non-immunized, type I collagen (CI) or type II collagen (CII)-immunized DBA/I J mice were injected into SCID mice which lack functional T and B cells. Specific antigenic stimulation of arthritogenic cells was required since only lymphocytes from arthritic CIA mice plus simultaneous administration of CII transferred arthritis to 11 of 12 SCID mice with a marked increase in CII antibody titre. However, CI-immunized or non-immunized DBA/IJ mice cells did not induce arthritis in SCID mice, SCID recipients of pre-arthritic CIA lymphocytes presented increase in CII antibody, but showed no clinical signs of arthritis, suggesting that antibodies to CII alone can not induce CIA. Depletion of CD4+ T cells inhibited the transfer of arthritis to SCID mice, with a decrease in CII antibody titre in chimaeras. In contrast, depletion of CD8+ cells enhanced the onset of arthritis in SCID mice. The results imply that CD4+ T cells are required for the induction of CIA. In addition, CD8 + T cells might have a suppressive role in the etiology of this disease. It is probable that memory CD4+ T cells stimulate production of antibodies to CII and subsequent arthritis. This study clarifies the role of T lymphocytes in the transfer of CIA lo SCID mice.
Heat shock protein peptides reactive in patients with Behçet's disease are uveitogenic in Lewis rats
Authors: STANFORD M R , KASP E , WHISTON R , HASAN A , TODRYK S , SHINNICK T , MIZUSHIMA Y , DUMONDE D C , VAN DER ZEE R , LEHNER T
Published: July 2010

Mycobacterial and homologous human heat shock protein T cell peptide epitopes specific for T lymphocytes in Behçets disease were investigated for their pathogenicity in Lewis rats. The potential pathogenicity of eight peptides and two controls was assessed by administering the peptides in enriched Freund's adjuvant into the footpads of male Lewis rats. Anterior uveitis which is a major manifestation of Behçet's disease was induced with two out of the four mycobacterial and all four homologous human peptides. The most effective peptides inducing indocyclitis in 64–75% of rats were peptides with amino acids 336–351 and 136–150, derived from the sequence of the human 60-kD heat shock protein. A few of the rats also showed evidence of focal loss of photoreceptors. These results suggest that selected peptides within heat shock protein 60 kD which function as T cell epitopes in Behçet's disease are capable of inducing uveitis in rats. This supports the view that the peptide T cell determinants may be involved in the pathogenesis of Behçet's disease.
Cytokine regulation of low-affinity IgE receptor (CD23) on monocytes from asthmatic subjects
Authors: VECCHIARELLI A , SIRACUSA A , MONARI C , PIETRELLA D , RETINI C , SEVERINI C
Published: July 2010

The regulation of CD23 expression (FcεRII) by cytokines on monocytes from normal subjects, asymptomatic and acute asthmatics was investigated. CD23 was weakly expressed on cells from controls, but was significantly enhanced in the two groups of asthmatics. The addition of IL-4 on monocytes induced an increase of CD23 expression in cells from controls and asthmatics. Interferon-gamma (IFN-γ) did not modulate CD23 expression in asthmatics or control subjects, while high doses of IL-6 (2000 U/ml) enhanced CD23 expression on cells from asthmatics or controls. In vitro stimulation of monocytes with Timothy grass pollen allergen did not enhance CD23 receptor in asthmatics with a positive skin test to this pollen. We speculate that CD23 expression in asthmatics is markedly enhanced by Th2-dependent cytokines, such as IL-4 and IL-6. Thus, the regulation of Th2 cell activation by anti-cytokine therapy could have an important effect on the down-regulation of CD23 on monocytes, and in shifting a Th2 subpopulation into a Th1 subpopulation by blocking Th2-dependent cytokines.
IgE production in atopic patients is not related to IL-4 production
Authors: VAN DER POUW KRAAN C T M , AALBERSE R C , AARDEN L A
Published: July 2010

To analyse whether there is a general defect in T or B cell function in atopic individuals we have measured cytokine and IgE production by peripheral blood lymphocytes, isolated from 19 atopic donors (17 asthma/rhinitis and two dermatitis patients) in comparison with 19 non-atopic controls. After stimulation of lymphocytes with anti-CD2 and anti-CD28, we found no significant difference in IL-2, IL-4 and interferon-gamma (IEN-γ) production. To examine the correlation between the production of IgE and IL-4, we stimulated lymphocytes with anti-CD2 and rIL-2. Under this condition both T cell IL-4 and B cell IgE production can be measured. No significant difference was found for the amount of IgE and IL-4 produced between the two groups (P > 0·05). The non-atopic donors showed a good correlation between IL-4 and IgE production (r= 0·70). Surprisingly, within the atopic group there was no correlation between IgE and IL-4 production at all (r= −0·04). The ratio of IgE to IL-4 was higher (although not significantly) in the atopic group. Our data suggest that in atopic donors IgE production is less dependent on IL-4, and that other cytokines are involved.
Multispecific and heterogeneous recognition of the gag protein by cytotoxic T lymphocytes (CTL) from HIV-infected patients: factors other than the MHC control the epitopic specificities
Authors: BUSEYNE F , JANVIER G , ELEURY B , SCHMIDT D , RIVIÈRE Y
Published: July 2010

The HIV gag polyprotein is a major target for recognition by CTL in infected humans. Using recombinant vaccinia viruses (rVV) expressing truncations of the p24gag, and the p18gag, p15gagand HIV-2 p56gag proteins, the characterization of epitope regions recognized by in vitro-stimulated peripheral blood mononuclear ceils (PBMC) from 18 infected patients has been studied. The gag-specific response of most individuals is polyclonal and multispecific, and inter-individual variations between target epitope regions were frequently observed, despite shared MHC alleles. As CTL may play an important role in the control of HIV replication in infected hosts, these results have important implications for designing vaccine strategies.
Cytokines in nasopharyngeal secretions; evidence for defective IL-1β production in children with recurrent episodes of acute otitis media
Authors: LINDBERG K , RYNNEL-DAGÖÖ B , SUNDQVIST K-G
Published: July 2010

The host-parasite relationship in the nasopharynx of young children with bacterial colonization and antigen uptake in the mucosa and lymphatic tissue provides an opportunity to investigate infectious inflammatory processes and responses. IL-1β, IL-6 and tumour necrosis factor-alpha (TNF-α) were analysed in nasopharyngeal secretions and serum from children with or without recurrent episodes of acute otitis media, from healthy adults and adults with hypogamma-globulinaemia or selective deficiency of IgG3. Nasopharyngeal secretions generally contained substantial amounts of IL-1β, IL-6 and TNF-α. In contrast. IL-1β, IL-6 and TNF-α were not detectable in sera on the same occasion. Children were found to have higher levels of IL-1β, IL-6 and TNF-α than healthy adults and than adults with immunodeficiency. High levels of IL-IJ were associated with low or undetectable levels of IL-6 and TNF-α, whereas the opposite pattern was seen in association with low levels of IL-lβ This was especially true for children with recurrent episodes of acute otitis media (RAOM). In children with nasopharyngeal colonization with Haemophilus influenzae, significantly higher levels of IL-1β, IL-6 and TNF-α (P = 00001. respectively) were found compared with non-colonized children. Notably, the RAOM children exhibited significantly lower levels of IL-1β IL-6, and TNF-α in nasopharyngeal secretions (P = 00001, 0.01 and 0.0001, respectively) than healthy children. These results demonstrate local production of inflammatory cytokines in nasopharynx, related to bacterial colonization, and suggest that children with RAOM are poor nasopharyngeal cytokine producers.
IL-1α gene expression and protein production by fibroblasts from patients with systemic sclerosis
Authors: KAWAGUCHI Y
Published: July 2010

We examined IL-1α and IL-1β gene expression and protein production in human dermal fibroblasts from patients with systemic sclerosis (SSc) to investigate the abnormal function of SSc fibroblasts. Human dermal fibroblasts were biopsied from 13 patients with SSc. three patients with rheumatoid arthritis (RA) and five healthy normal controls (NC). Cells were cultured in serum-free media and total RNA was collected from second or third passage fibroblasts. In cultured SSc fibroblasts. IL-1α and IL-1β mRNAs were constitutively expressed and intracellular pro-IL-1α was present. These observations suggest that an autocrine effect of IL-1α contributes to the fibrosis in SSc.
The IgE and IgG antibody responses to aerosols of Nephrops norvegicus (prawn) antigens: the association with clinical hypersensitivity and with cigarette smoking
Authors: McSHARRY C , ANDERSON K , McKAY I C , COLLOFF M J , FEYERABEND C , WILSON R B , WILKINSON P C
Published: July 2010

Raised levels of serum IgE antibodies to prawn antigens were found in 15 of 26 seafood factory process workers with respiratory symptoms and in one of 26 case-matched asymptomatic controls (P < 0.001). Raised IgG antibody titres against the same antigens were found in 18 subjects in each symptom grouping, and the median titres of this antibody did not differ significantly between the groups. The prawn-specific IgE antibody response was significantly associated with atopy (IgE antibody response to common allergens) and with a history of cigarette smoking, confirmed by level of serum cotinine, a major nicotine metabolite. Non-atopic non-smokers were unlikely to become sensitized. The titre of the prawn-specific IgE antibody correlated with the duration of exposure and with the duration of symptoms. Discriminant analysis of the serological profile (anti-prawn IgE, total IgE and cotinine) was sufficient to assign individuals correctly into symptomatic or asymptomatic categories in 77% of subjects. The titres of the IgE and IgG antibody responses to prawn antigens did not correlate, and the main factor which seemed to determine the antibody isotype response to these inhaled antigens was cigarette smoking. IgE antibody was produced mainly by smokers, whereas IgG antibody was the predominant isotype produced by non-smokers.
Increase in the proportion of granulated CD56+ T cells in patients with malignancy
Authors: TAKII Y , HASHIMOTO S , IIAI T , WATANABE H , HATAKEYAMA K , ABO T
Published: July 2010

Evidence is presented for the existence of a unique T cell population which expressed one of the natural killer (NK) markers, CD56 antigen, in humans. Although such 0056+ T cells were a minor population in the peripheral blood (< 10%). They were abundant in the liver (up to 50%). which was recently demonstrated to be a major organ for extrathymic T cell differentiation in mice. As in the case of extrathymic T cells in mice, these CD56+ T cells in humans contained a higher proportion of γδ cells than did CD56− T cells, contained double-negative CD4−8 cells, and had the morphology of large granular lymphocytes. This unique population of CD56+ T cells tended to be elevated in the blood and among tumour-infiltrating lymphocytes in patients with colorectal cancer, especially in advanced cases. These results raise the possibility that, as in mice, CD56+ T cells with extrathymic T cell properties may also be associated with tumour immunity in humans.
HIV-1 recombinant gp160 vaccine given in accelerated dose schedules
Authors: GORSE G J , SCHWARTZ D H , GRAHAM B S , MATTHEWS T J , STABLEIN D M , FREY S E , BELSHE R B , CLEMENTS M L , WRIGHT P F , EIBL M , FAST P E
Published: July 2010

The purpose of this randomized, double-blind study was to test the safely and immunogenicity of an HIV-ILAI recombinant gp160 (rgp160) vaccine in healthy, uninfected volunteers using accelerated dosing schedules. Thirty volunteers were randomly assigned lo receive 50μg doses of rgp160 in one of two immunization schedules. Group 1 received rgp160 at times 0, 1, 2 and 5 months: and group 2 received rgp160 at times 0, 1, 2, 3 and 4 months. The vaccine was safe and stimulated high levels of HIV-1 envelope-specific binding antibody and T cell memory. There was a trend (P < 0.10) suggesting neutralizing antibodies were better induced by the regimen incorporating a rest period before the final immunization in group 1 volunteers. Both accelerated immunization schedules induced immune responses at levels similar to or better than those achieved by four rgp160 vaccine injections given over 12-18 months in other studies.