bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming growth factor-beta 1 (TGF-β1) expression in ovine lentivirus-induced lymphoid interstitial pneumonia
Authors: Moreno B , Woodall C J , Watt N J , Harkiss G D 
Published: March 2003

SUMMARY
The aim of this study was to detect the localization of TGF-β1 protein expression in normal sheep lungs and lungs with interstitial pneumonia associated with infection with maedi-visna virus (MVV). Immunohistochemical localization of TGF-β1 was determined in 24 lungs of adult sheep naturally infected with MVV and six control lungs of seronegative sheep. The lungs of infected animals showed different lesional degrees: grade 0, no lesions; grade I, mild; grade II, moderate; grade III, severe. In normal lungs, TGF-β1 was primarily expressed in airway epithelium, bronchial cartilage and glands, endothelial cells and smooth muscle of blood vessels, alveolar macrophages and type II pneumocytes. No staining was observed in alveolar interstitium. In MVV-infected sheep an increased number of positive alveolar and interstitial macrophages and staining of alveolar interstitium was observed in grade I, grade II and some grade III lesions. In grade III lesions an inverse relationship was found between TGF-β1 staining and smooth muscle hyperplasia. Small lymphoid aggregates, in general, showed strong reactivity, whereas larger ones showed weak reactivity, mainly associated with follicular areas. No significant differences in the staining intensity of airways and blood vessels were observed between control and MVV lungs. The increased expression of TGF-β1 in early maedi lesions and its down-regulation in more advanced disease suggest the operation of a temporal regulatory mechanism whereby early expression may lead to the smooth muscle hyperplasia which develops during the disease. The striking inverse relationship between TGF-β1 expression and follicle organization is intriguing and warrants further investigation.
HIV-1 does not alterin vitroandin vivoIL-10 production by human monocytes and macrophages
Authors: Bergamini A , Bolacchi F , Faggioli E , Placido R , Vendetti S , Cappannoli L , Ventura L , Cerasari G , Uccella I , Andreoni M , Rocchi G 
Published: March 2003

SUMMARYThe present study analyses the ability of HIV-1 to modulate IL-10 production in cells of monocyte-macrophage lineage cultured in the presence of macrophage colony-stimulating factor (M-CSF). Both monocytes and macrophages spontaneously produced low amount of IL-10. Lipopolysaccharide (LPS) induced a strong IL-10 response in fresh monocytes and in M-CSF-treated macrophages. In contrast, macrophages cultured in the absence of M-CSF exhibited a marked decrease in their susceptibility to LPS stimulation. M-CSF increased the IL-10 response of macrophages to LPS by enhancing both the expression of membrane-bound CD14, the protein that serves as LPS receptor, and the sensibility of CD14-expressing cells to LPS stimulation. Neither spontaneous nor LPS-induced expression of IL-10 was modulated in monocytes and macrophages by infection with eight monocytotropic strains, as demonstrated by ELISA and cytofluorimetric analysis. In contrast, all the HIV-1 strains primed macrophages for an increased IL-6 response to LPS stimulation. To determine whether IL-10 production was associated with in vivo infection, monocytes from AIDS individuals were analysed for IL-10 production. We found that neither spontaneous nor LPS-induced IL-10 production were different between healthy controls and HIV-infected patients. Taken together, these data strongly suggest that HIV-1 infection of monocytes-macrophages does not play a significant role in the regulation of IL-10 in infected patients. This study also emphasizes the role of M-CSF activation in the regulation of the cytokine response in macrophages.
Elevated serum levels of soluble Fas/APO-1 (CD95) in patients with hepatocellular carcinoma
Authors: Jodo S , Kobayashi S , Nakajima Y , Matsunaga T , Nakayama N , Ogura N , Kayagaki N , Okumura K , Koike T 
Published: March 2003

SUMMARYFas (APO-1/CD95)-mediated apoptosis plays an important role in liver cell destruction in viral hepatitis. Using sandwich ELISA, we measured serum levels of soluble Fas (sFas) in patients with hepatocellular carcinoma (HCC) who were positive for hepatitis B surface antigen (HBsAg) or anti-hepatitis C virus (HCV) antibody. sFas levels were significantly higher in HCC patients (median 4·07 ng/ml; range 0·14–29·18 ng/ml) than levels in age-matched healthy donors (0·29 ng/ml; 0–4·90 ng/ml) (P &lt; 0·0001) and HBsAg or anti-HCV antibody-positive patients with liver cirrhosis (LC) (2·16 ng/ml; 0·24–8·39 ng/ml) (P = 0·0015). An arbitrary cut-off level of 3·03 ng/ml (mean + 3 s.d. of controls) revealed the positive frequency of sFas in each group: 1·7% in healthy subjects, 25·9% in LC, and 59·0% in HCC (sensitivity 59·0% and specificity 74·1%). All HCC sera tested contained transmembrane-deleted sFas and some contained another sFas lacking the Fas C-terminal. The positive frequency of either sFas (59·0%) or α-fetoprotein (AFP) (57·4%) in HCC patients reached 77·0%. HCC patients with multiple tumour foci (7·53 ng/ml; 1·40–29·18 ng/ml) had significantly higher sFas levels than did patients with a solitary tumour (2·70 ng/ml; 0·14–19·0 ng/ml) (P = 0·003). In all of the sFas-positive patients with a solitary tumour, surgical removal of the tumour reduced sFas levels to the negative in the first post-op week. These findings suggest that sFas may be closely linked with HCC and may be a candidate for a clinical parameter for HCC.
Decay-accelerating factor (DAF) in stool specimens as a marker of disease activity in patients with ulcerative colitis (UC)
Authors: Inaba T , Mizuno M , Ohya S , Kawada M , Uesu T , Nasu J , Takeuchi K , Nakagawa M , Okada H , Fujita T , Tsuji T 
Published: March 2003

SUMMARYColonic epithelial cells of patients with UC express DAF in relation to the severity of mucosal inflammation. The aim of this study was to determine whether this factor in stool could be used as a marker of disease activity in UC patients. Stool DAF was measured by use of an immunoassay in 181 stool specimens obtained from 55 patients with UC of various levels of disease activity. Stool DAF concentrations in patients whose UC was active (0·0–785·6 ng/g stool; median 47·1 ng/g; n = 115) were significantly higher than concentrations in patients whose disease was inactive (0·0–48·6 ng/g; median 0·0 ng/g; n = 66) (P &lt; 0·0001). Values in active UC patients also were higher than those in control patients with diarrhoea (0·0–30·0 ng/g; median 0·0 ng/g; n = 26) (P &lt; 0·0001) and in control subjects without apparent colorectal disease (0–20·4 ng/g; median 0·0 ng/g; n = 44) (P &lt; 0·0001). The elevated levels of stool DAF obtained from UC patients in relapse declined markedly in specimens collected after the disease went into remission following medical therapy. Stool DAF levels correlated with the severity of endoscopic and histological findings and the degree of DAF expression on the colonic epithelia. Our results suggest that the measurement of stool DAF is useful as a non-invasive means of monitoring intestinal disease activity in patients with UC.
Analysis of graft-versus-host disease (GVHD) and graft rejection using MHC class I-deficient mice
Authors: Shenoy S , Desch K , Duffy B , Thorson P , Mohanakumar T 
Published: March 2003

SUMMARYGVHD is a major complication in allogeneic bone marrow transplantation (BMT). MHC class I mismatching increases GVHD, but in MHC-matched BMT minor histocompatibility antigens (mH) presented by MHC class I result in significant GVHD. To examine the modification of GVHD in the absence of cell surface MHC class I molecules, β2-microglobulin-deficient mice (β2m-/-) were used as allogeneic BMT recipients in MHC- and mH-mismatched transplants. β2m-/- mice accepted MHC class I-expressing BM grafts and developed significant GVHD. MHC (H-2)-mismatched recipients developed acute lethal GVHD. In contrast, animals transplanted across mH barriers developed indolent chronic disease that was eventually fatal. Engrafted splenic T cells in all β2m-/- recipients were predominantly CD3+ αβ TCR+ CD4+ cells (15–20% of all splenocytes). In contrast, CD8+ cells engrafted in very small numbers (1–5%) irrespective of the degree of MHC mismatching. T cells proliferated against recipient strain antigens and recognized recipient strain targets in cytolytic assays. Cytolysis was blocked by anti-MHC class II but not anti-CD8 or anti-MHC class I monoclonal antibodies (MoAbs). Cytolytic CD4+ T cells induced and maintained GVHD in mH-mismatched β2m-/- mice, supporting endogenous mH presentation solely by MHC class II. Conversely, haematopoietic β2m-/- cells were unable to engraft in normal MHC-matched recipients, presumably due to natural killer (NK)-mediated rejection of class I-negative cells. Donor-derived lymphokine-activated killer cells (LAK) were unable to overcome graft rejection (GR) and support engraftment.
Deoxyspergualin preferentially inhibits the growth and maturation of anti-CD40-activated surface IgD+ B lymphocytes
Authors: Morikawa K , Nemoto K , Miyawaki T , Morikawa S 
Published: March 2003

SUMMARYDeoxyspergualin (DSG), an analogue of spermidin, is a potent immunosuppressive drug with an action quite distinct from that of cyclosporin, rapamycin, or FK506. In this study we investigated the effect of DSG and methyldeoxyspergualin (MeDSG) on the proliferation and differentiation of human B cells stimulated with anti-CD40 MoAb. Highly purified B cells obtained from tonsillar samples were used as target cells. Both agents inhibited the proliferative response of anti-CD40-stimulated B cells in the absence and presence of IL-4, IL-2 or IL-10 in a dose-dependent manner. This inhibitory effect differed markedly among cell populations based on surface IgD expression: strong inhibition of sIgD+ B cells but little inhibition of sIgD− B cells. The drugs also suppressed the production of IgG, IgM and IgA by unfractionated B cells, which suggests that DSG acts against post-switch (sIgD−) B cells. Although the drugs suppressed immunoglobulin synthesis by both sIgD+ and sIgD− B cells, the effect was more marked in the sIgD+ B cells. Analysis of the subclass of IgG secreted by slgD+ B cells revealed a decline in IgG1 and IgG3 in the presence of DSG. These results suggest that DSG preferentially inhibits the growth and maturation of sIgD+ naive B cells.
Neoplastic thymic epithelial cells of human thymoma support T cell development from CD4−CD8− cells to CD4+CD8+ cellsin vitro
Authors: Inoue M , Fujii Y , Okumura M , Takeuchi Y , Shiono H , Miyoshi S , Matsuda H , Shirakura R 
Published: March 2003

SUMMARYHuman thymoma is a thymic epithelial cell tumour which often contains a large number of immature T cells and is frequently associated with autoimmune diseases. Since thymic epithelial cells play key roles in the development and selection of T cells in the normal thymus, we hypothesized that the neoplastic thymic epithelial cells of thymoma may support T cell differentiation in the tumour. We characterized CD4−CD8− cells in thymoma and applied an in vitro reconstitution culture system using the CD4−CD8− cells and the neoplastic epithelial cells isolated from thymoma. CD34, a stem cell marker, was expressed on 29.9 ± 12.2% of CD4−CD8− cells in thymoma. TCRγδ was expressed on 27.4 ± 15.1% of CD4−CD8− cells and CD19, a B cell marker, was expressed on 14.1 ± 23.1% of CD4−CD8− cells. CD4−CD8− cells expressed both IL-7R α-chain and common γ-chain. Purified CD4−CD8− cells from thymomas were cultured with the neoplastic epithelial cells, and their differentiation into CD4+CD8+ cells via CD4 single-positive intermediates was observed within 9 days' co-culture in the presence of recombinant IL-7. Furthermore, we examined the reconstitution culture using CD34+CD4−CD8− cells purified from normal infant thymus. The CD34+CD4−CD8− cells in normal thymus also differentiated to CD4+CD8+ cells in the allogeneic co-culture with the neoplastic epithelial cells of thymoma. These results indicate that the tumour cells of thymoma retain the function of thymic epithelial cells and can induce differentiation of T cells in thymoma.
Analysis of orbital T cells in thyroid-associated ophthalmopathy
Authors: Förster G , Otto E , Hansen C , Ochs K , Kahaly G 
Published: March 2003

SUMMARYThyroid-associated ophthalmopathy (TAO) has a major effect on the two compartments of the retro-orbital (RO) space, leading to enlargement of the extraocular muscles and other RO tissues. T lymphocyte infiltration of RO tissue is a characteristic feature of TAO and there is current interest in whether these T cells are specifically and selectively reactive to RO tissue itself. We recently established 18 T cell lines (TCL) from RO adipose/connective tissue of six patients with severe TAO by using IL-2, anti-CD3 antibodies and irradiated autologous peripheral blood mononuclear cells (PBMC) to maintain the growth of T cells reactive to autologous RO tissue protein fractions. Here we report on the phenotype characteristics and cytokine gene expression profiles of these orbital TCL and on their immunoreactivity to the organ-specific thyroid antigens thyrotropin receptor (TSH-R), thyroidal peroxidase (TPO) and thyroglobulin (TG). Flow cytometry revealed that 10 TCL were predominantly of CD4+ phenotype, three being mostly CD8+ and five neither CD4+ nor CD8+. Analysis with reverse transcriptase-polymerase chain reaction (RT-PCR) of cytokine gene expression revealed both Th1- and Th2-like products in all TCL: IL-2 product (in 17 TCL), interferon-gamma (IFN-γ) (n = 10), tumour necrosis factor-beta (TNF-β) (n = 15), IL-4 (n = 12), IL-5 (n = 17), IL-6 (n = 13), TNF-α (n = 12) and IL-10 (n = 4). Reactivity to thyroid antigens was observed only in two TCL, the other 16 being uniformly unreactive. Although 10 out of 18 RO tissue-reactive TCL were predominantly CD4+ there were no significant relationships between TCL phenotype, cytokine gene profile, magnitude of reactivity to RO tissue protein or the (rare) occurrence of thyroid reactivity. The findings of both Th1- and Th2-like cytokine gene expression in all RO tissue-reactive TCL support the concept that TAO is a tissue-specific autoimmune disease, distinct immunologically from the thyroid, and involving both T cell and B cell autoimmune mechanisms in disease pathogenesis.
No evidence for abnormal immune activation in peripheral blood T cells in patients with hepatitis C virus (HCV) infection with or without cryoglobulinaemia
Authors:   MULTIVIRC GROUP, Cacoub P , Musset L , Hausfater P , Ghillani P , Fabiani F L , Charlotte F , Angevin E , Opolon P , Poynard T , Piette J-C , Autran B 
Published: March 2003

AbstractThe aim of this study was to investigate the peripheral blood lymphocyte (PBL) phenotypes and T cell repertoire in patients with HCV infection, with or without mixed cryoglobulinaemia (MC). The patients were: Group 1, 23 patients with HCV infection and MC; Group 2, 14 patients with HCV infection but without MC; Group 3, 10 patients with symptomatic essential MC. Twenty healthy blood donors were used as controls. Blood lymphocyte counts were determined, and flow cytometry was used to measure proportions of B cells (CD19+), natural killer (NK) cells (CD16+ CD56+), T cells (CD3+), CD4+ T cell subsets (memory CD4+ CD45RO+; naive CD4+ CD45RO−; Th0/Th2 CD4+ CD7−; activated CD4+ CD25+), and CD8+ T cell subsets (immunoregulatory CD8+ CD57+; cytotoxic CD8+ S6F1+, activated CD8+ CD25+). Bias in the usage of T cell receptor (TCR) Vβ chains was studied in a subgroup of 10 representative patients of Group 1 using a polymerase chain reaction (PCR) analysis of the Vβ segments with a series of 20 oligonucleotides specific for the Vβ families. The three groups were comparable for blood lymphocyte counts, and we observed no abnormal repartition of the following PBL subsets: T cells (CD3+), CD4+ and CD8+ subpopulations, B cells (CD19+), and the NK cells (CD16+ 56+). In none of the groups could we observe lymphocyte ex vivo activation as assessed by the normal expression of the activation cell markers: CD25 on CD4+ or CD8+ T cells, or CD5 on B cells. The repartition of naive and memory (CD45RO−/RO+) CD4+ T cells was normal and we did not observe any amplification of the CD4+ CD7− T cell subset differentiated in vivo in Th0/Th2 cells. There was no significant amplification of cytotoxic (SF6+) and immunoregulatory (CD57+) CD8+ T cells in HCV patients with or without MC. Finally, the usage of Vβ families in the TCR repertoire was normal in the patients tested. In patients with chronic HCV infection, with or without MC, we did not find any significant expansion or abnormal activation of T, B and NK cell subsets, dysbalance of the naive/memory subsets, or expansion of the Th0/Th2 subpopulation. These findings differ from the profound immune alterations that are observed in other chronic infections such as HIV or Epstein–Barr virus. Although this study was restricted to the peripheral blood, it suggests that in chronic HCV infection, MC is not the consequence of a chronic activation or dysregulation of the peripheral blood immune cells.
Expansion of CD56+ NK T and γδ T cells from cord blood of human neonates
Authors: Musha N , Yoshida Y , Sugahara S , Yamagiwa S , Koya T , Watanabe H , Hatakeyama K , Abo T 
Published: March 2003

SUMMARYA particular T cell population expressing NK cell markers, CD56 and CD57, exists in humans. Many CD56+ T and CD57+ T cells (i.e. NK T cells) exist in the liver and increase in number in the blood with ageing. They may be a human counterpart of extrathymic T cells, similar to NK1.1+ CD3int cells seen in mice. We investigate here the existence of such NK T cells in human cord blood and the in vitro expansion of these cells by the stimulation of human recombinant IL-2 (rIL-2). There were very small populations (&lt; 1.0%) of CD56+ T cells, CD57+ T cells, and γδ T cells in cord blood. However, all of these populations increased in number after birth and with ageing. When lymphocytes in cord blood were cultured with rIL-2 (100 U/ml) for 14 days, CD56+ T cells expanded up to 25% of T cells. CD57+ T cells were never expanded by these in vitro cultures. The expansion of γδ T cells (mainly Vγ9− non-adult type) also occurred in the in vitro culture. A considerable proportion of CD56+ T cells was found to use Vα24 (i.e. equivalent to invariant Vα14 chain used by murine NK T cells) for TCR αβ. These results suggest that neonatal blood contains only a few NK T cells but CD56+ NK T cells and γδ T cells are able to expand in vitro.
Effects of monoclonal antibodies to adhesion molecules on eosinophilic myocarditis inToxocara canis-infected CBA/J mice
Authors: Hokibara S , Takamoto M , Isobe M , Sugane K 
Published: March 2003

SUMMARYEosinophilic myocarditis followed by fibrosis of the cardiac muscle was observed in addition to peripheral blood eosinophilia in CBA/J mice infected with Toxocara canis. The infected mice were used as an experimental model of eosinophilic endomyocarditis associated with hypereosinophilic syndrome. Effects of in vivo treatment with MoAbs to adhesion molecules on eosinophilic myocarditis were examined using this experimental model. Expressions of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on endothelial cells of capillaries in myocardium were increased 1 and 2 weeks after infection. Infiltration of very late antigen (VLA)-4+ and/or CD11a+ cells into the cardiac muscles was also observed 1 and 2 weeks after infection. Infiltration of eosinophils into the heart was significantly suppressed by anti-CD18 MoAb and anti-VLA-4 MoAb, and focal fibrosis of the cardiac muscle was also significantly suppressed by combined administration of anti-CD18 and anti-ICAM-1 MoAbs. These results indicate that adhesion molecules may play important roles in eosinophilic myocarditis, and that blockade of interaction between adhesion molecules and their ligands may help to control it.
FcγRIa–γ-chain complexes trigger antibody-dependent cell-mediated cytotoxicity (ADCC) in CD5+ B cell/macrophage IIA1.6 cells
Authors: Van Vugt M J , Van Den Herik-Oudijk I E , Van De Winkel J G J 
Published: March 2003

SUMMARYMost receptors for immunoglobulins exist as multi-subunit complexes, with unique ligand binding α-chains, combined with accessory signalling (γ-, β-, or ζ-) chains. The myeloid class I receptor for IgG (FcγRIa) has been shown to be dependent on the FcR γ-chain for surface expression in vivo. In this study we assess the capacity of FcγRIa–γ-chain complexes expressed in IIA1.6 cells to trigger phagocytosis and ADCC. An intact immunoreceptor tyrosine-based activation motif (ITAM) signalling motif proved essential for triggering of biological function via the FcγRIa receptor complex. Both the FcR γ-chain and the FcγRIIa–ITAM proved active in directing phagocytosis of Staphylococcus aureus and ADCC of erythrocytes, triggered by the FcγRIa complex. The capacity of FcγRIa to trigger phagocytic and cytolytic activity by IIA1.6 cells, both considered ‘professional phagocyte’ functions, motivated us to re-evaluate the cell lineage and developmental stage of IIA1.6 cells. Although originally described as mouse B lymphocytes, the IIA1.6 cells proved positive for non-specific esterase activity and expressed the CD5 antigen. These combined characteristics place the IIA1.6 cells within a unique CD5+ B cell/macrophage lineage, optimally suited for cell biological analyses of phagocyte receptors.
Study of antigenic sites on the asialoglycoprotein receptor recognized by autoantibodies
Authors: Hajoui O , Martin S , Alvarez F 
Published: March 2003

SUMMARY
The aim of this study was to identify the epitopes recognized by antibodies to the asialoglycoprotein receptor, a specific hepatocyte protein, from sera of patients with autoimmune hepatitis. An ELISA test was used to detect anti-asialoglycoprotein receptor antibodies in the sera of patients with autoimmune hepatitis. Positive sera were tested against the same antigen by slot blot, by Western blot and by immunoprecipitation of the untreated protein and following treatment with β-mercaptoethanol (β-ME) and endoglycosidase F. The mature, unglycosylated and partially glycosylated forms of the asialoglycoprotein receptor synthesized by HepG2 cells were tested against positive patients' sera, as well as the in vitro translated unglycosylated form of the H1 subunit of the receptor. Sera from patients with autoimmune hepatitis recognized equally the native form, as well as the β-ME-modified form, but less well the deglycosylated form of the human mature receptor. No reactivity was found when these sera were tested against the denatured human protein. In addition, neither the unglycosylated H1 subunit nor any of the HepG2-synthesized asialoglycoprotein receptor forms bound to the antibodies. Altogether, these results show that anti-asialoglycoprotein receptor antibodies in the sera of patients with autoimmune hepatitis are directed against conformational structures of the mature hetero-oligomeric form of the human liver protein and that at least some epitopes were located on the extracellular domain of the antigen.