bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ketotifen therapy in chronic graft-versus-host disease (cGVHD): effect on mast cells and fibroblasts
Authors: NAGLER A , SEGAL V , SLAVIN S , LEVI-SCHAFFER F 
Published: July 2010

SUMMARYCurrent treatment options for cGVHD are limited. Mast cells (MC) and fibroblasts have been shown to play a role in the murine model of cGVHD. Ketotifen is an anti-H-1 antihistamine with MC-stabilizing properties. We therefore treated eight patients with cGVHD with ketotifen (6μg/ day for 3 months). Three additional age- and sex-matched cGVHD patients served as controls. MC count and activation state in cGVHD skin biopsies and the in vitro effect of peripheral blood mononuclear cell (PBMC) supernatants on (i) histamine release by MC; (ii) 3T3-fibroblast proliferation; and (iii) prostaglandin E2 (PGE2) production, were evaluated. Ketotifen therapy resulted in clinical improvement in 4/8 patients, stabilization of the disease in 2/8, while in 2/8 patients the cGVHD progressed and they died of bacterial sepsis. Side effects were minimal. In the skin biopsies the number of MC was found to be 0.58±0.17 (n= 8) (field ± 400) and the MC looked degranulated (toluidine blue staining). Following ketotifen therapy MC number was increased to 1.2±0.28 (n= 8) (P &lt; 0.05). PBMC supernatants of cGVHD patients stimulated histamine release from cultured rat MC(n= 8)(2.7±0.5 μg/ml; normal values are 2±1.0±4 μg/ml, n = 5). Ketotifen therapy reduced the histamine release level to the normal range (2.0±0.5 μg/ml, P &lt; 0.05) (n= 8). Ketotifen therapy had no significant effect on; (i) 3T3 fibroblast proliferation which was suppressed by cGVHD PBMC supernatants; (ii) the elevated PGE2 production which we observed when fibroblasts were incubated with the PBMC supernatants. These results indicate that ketotifen may play a therapeutic role in cGVHD.
Dengue virus-induced human cytotoxic factor: production by peripheral blood leucocytesin vitro
Authors: Mukerjee R , Chaturvedi U C , Dhawan R 
Published: July 2010

SUMMARYDuring dengue type 2 virus (DV) infection of mice a unique cytokine, the cytotoxic factor (CF), is produced which reproduces the pathological lesions seen in patients of dengue haemorrhagic fever (DHF). Recently we have observed a CF-like protein in the sera of DHF cases. The present study was undertaken to investigate whether DV can stimulate human peripheral blood mononuclear cells (PBMC) in vitro to produce human CF (hCF). Cultures prepared from PBMC or its enriched subpopulations were inoculated with 1000 LD50 of DV and controls with normal mouse brain suspension (NMB). Aliquots of cultures were harvested daily from 24 h to 96 h and their supernatant (CS) and cells were separated. CS were screened for viral titres and for the presence of hCF by cytotoxicity assay, inhibition ELISA, dot blot and Western blot tests using anti-mouse-CF antibodies. The RNA from the cells was screened in Northern blot and dot blot tests for the presence of mRNA for CF. It was observed that hCF appeared in the CS of DV-infected culture of PBMC and T-enriched cells at 48 h and was present until 96 h; no CF was detected in CS of B cells or monocyte cultures. The production of hCF was abrogated by pretreatment of the T cells with anti-CD4 antibodies but not with anti-CDS antibodies, indicating that hCF was produced by CD4 T cells. The Northern blot analysis using oligonucleotide probes prepared on the basis of amino-terminal sequence of mouse CF, showed presence of mRNA for hCF in PBMC and T cell cultures. DV replicated in PBMC cultures with peak titres at 48 h. The findings of the present study demonstrate that DV-induced hCF is produced by human T cells.
Insulin-like growth factor-1 (IGF-1) protects NOD mice from insulitis and diabetes
Authors: Bergerot I , Fabien N , Maguer V , Thivolet C 
Published: July 2010

SUMMARYTo evaluate the effect of IGF-1 on the autoimmune process of d cell destruction, permissive non-obese diabetic (NOD) recipients were adoptively transferred with 7 × 106 autoreactive T cells from diabetic NOD mice and were administered subcutaneously 10μ;g rhIGF-1, twice daily for 3 weeks. Administration of rhIGF-1 reduced the final incidence of successful transfers of diabetes observed in only 6/24 mice (25%) versus 12/21 (57%) in control mice. A marked reduction of insulitis during histological analysis of pancreatic glands was also observed. Mice treated with rhIGF-1 had a higher percentage of intact islets (486 ± 12% versus 16 ± 1·1%. P= 0·001) and a lower percentage of infiltrated islets. Islets from rhIGF-1-treated mice had a more intense insulin staining reflecting a higher β cell mass, but no difference was observed in the amount of insulin content of pancreatic extracts and in the amounts of mRNA transcripts for proinsulin. No difference was also observed in the titres of three islet cell antibody (ICA)-positive sera and in the pattern of A2B5 staining. Some mice developed diabetes and severe islet cell infiltration despite rhIGF-1, thus indicating that some committed T cells were still able to invade the islets and cause β cell destruction. The percentages of CD4+ and CD8+ T cells in the spleen of experimental mice were similar. To evaluate the effects of rhIGF-1 on cell trafficking in recipient mice, T cells from diabetic NOD Thy-1,2 mice injected into congenic NOD-N Thy-1,1 mice were monitored 3 weeks after adoptive cell transfer. The percentage of Thy-1,2+ T cells was significantly reduced in the spleen (10·8 ± 1·3%versus 17·2 ± 3·9%, P= 0·004) of rhIGF-1 treated mice in contrast to the thymus (68·4 ± 7·9%versus 72·87 ± 6·2%, P= 0·306), suggesting that rhIGF-1 could influence T cell trafficking to the lymphoid organs. The findings that rhIGF-1 has protective effects in autoimmune diabetes opens new perspectives for future experiments as well as for preventive strategies in human type I diabetes.
Allelic polymorphism in IL-1β and IL-1 receptor antagonist (IL-1Ra) genes in inflammatory bowel disease
Authors: Bioque G , Crusius J B A , Koutroubakis I , Bouma G , Kostense P J , Meuwissen S G M , PeÑA AS 
Published: July 2010

SUMMARY
Recent reports have shown that allele 2 of the IL-1 receptor antagonist (IL-1Ra) gene is over-represented in ulcerative colitis (UC). Healthy individuals carrying allele 2 of this gene have increased production of IL-1Ra protein. Since the final outcome of the biological effects of IL-1β may depend on the relative proportion of these two cytokines, we have studied if a TaqI polymorphism in the IL-1β gene, which is relevant to IL-1β protein production, may be involved in the genetic susceptibility to UC and Crohn's disease (CD), in association with the established IL-1Ra gene polymorphism. Polymorphisms in the closely linked genes for IL-1β and IL-1Ra were typed in 100 unrelated Dutch patients with UC, 79 with CD, and 71 healthy controls. The polymorphic regions in exon 5 of the IL-1β gene and in intron 2 of the IL-1Ra gene, were studied by polymerase chain reaction (PCR)-based methods. The IL-1β allele frequencies in UC and CD patients did not differ from those in healthy controls. In order to study if the IL-1β gene polymorphism might participate synergistically with the IL-1Ra gene polymorphism in susceptibility to UC and CD, individuals were distributed into carriers and non-carriers of allele 2 of the genes encoding IL-1β and IL-1Ra, in each of the patient groups and controls. Results indicated a significant association of this pair of genes, estimated by the odds ratio (OR) after performing Fisher's exact test, in the UC group (P= 0·023, OR = 2·81), as well as in the CD group (P= 0·01, OR = 3·79). Thus, non-carriers of IL-1β allele 2 were more often present in the subgroup of patients carrying the IL-1Ra allele 2. By contrast, no association of these alleles was detected in the group of healthy controls (P= 1·00, OR = 0·92). These results suggest that the IL-1β/IL-1Ra allelic cluster may participate in defining the biological basis of predisposition to chronic inflammatory bowel diseases.
Dual action of IL-4 on mite antigen-induced IgE synthesis in lymphocytes from individuals with bronchial asthma
Authors: Kawano Y , Noma T 
Published: July 2010

SUMMARYPolyclonal IgE synthesis was efficiently induced by Dermatophagoides farinae (Df) antigen in freshly derived peripheral blood lymphocytes from mite-sensitive individuals with bronchial asthma. The in vitro IgE production was significantly correlated with total serum IgE values. The induced IgE synthesis was inhibited in a dose-dependent manner by antibodies to IL-4, indicating a role for endogenous IL-4. Although IL-4 alone increased IgE production, high concentrations (1–100 U/ml) of the cytokine inhibited Df antigen-stimulated production of IgE. However, low concentrations (0·001-0·01 U/ml) of IL-4 significantly enhanced Df antigen-induced IgE production, as did high doses of IL-4 when endogenous IL-4 was neutralized by antibodies to IL-4. Two other cytokines, IL-10 and interferon-gamma (IFN-γ), showed contrasting actions, as judged from experiments with exogenous cytokine and anti-cytokine antibodies: IL-10 enhanced and IFN-γ inhibited Df antigen-induced IgE synthesis. Thus, mite-stimulated IgE production in lymphocytes from individuals with bronchial asthma appears to be regulated by at least three cytokines; TL-4, IL-10, and IFN-γ.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) reduces toxoplasmastatic activity of human monocytes via induction of prostaglandin E2 (PGE2)
Authors: Delemarre F G A , Stevenhagen A , Van Furth R 
Published: July 2010

SUMMARYIn this study we investigated the effect of human GM-CSF on the toxoplasmastatic activity and release of H2O2 and PGE2 by human monocytes. Incubation of monocytes from healthy controls with GM-CSF resulted in a dose-dependent reduction of toxoplasmastatic activity and a decrease in H2O2 production. Furthermore GM-CSF-treated monocytes released more PGE2 than untreated cells. To investigate the role of PGE2 in the reduced toxoplasmastatic activity of GM-CSF-treated monocytes, these cells were incubated with indomethacin. This resulted in a reduction of PGE2 release and restoration of toxoplasmastatic activity of monocytes treated with GM-CSF. GM-CSF reduces the toxoplasmastatic activity of monocytes via production of PGE2.
Lipopolysaccharide (LPS) down-regulates CD4 expression in primary human macrophages through induction of endogenous tumour necrosis factor (TNF) and IL-1β
Authors: Herbein G , Doyle A G , Montaner L J , Gordon S 
Published: July 2010

SUMMARYThe regulation of CD4 expression on macrophages and its role in immune cell interactions remain obscure. In contrast with primary lymphocytes, primary macrophages express only low amounts of surface CD4, which is regulated differentially for example by adherence in vitro. We report that addition of LPS for 1–5 days to human blood monocyte tissue culture-derived macrophages (TCDM) down-regulates both surface CD4 expression and total cellular CD4 antigen content as measured by flow cytometry and Western blot analysis. TNF-α and IL-1β, proinflammatory cytokines which are both induced by LPS. also down-regulate surface and total CD4 expression in TCDM, This down-regulation of CD4 expression by LPS, TNF-α, and IL-1β occurs at the level of transcription. The decreased macrophage CD4 expression induced by LPS was blocked by MoAbs directed against human TNF-α and IL-1β, demonstrating that LPS acts on CD4 expression through induction of endogenous TNF-α and IL-1β. Conversely, neither LPS nor TNF-α and IL-1β were able to modulate surface CD4 expression on quiescent or phytohaemagglutinin (PHA)-activated lymphocytes. Of other cytokines and growth factors tested, Th2 cytokines (IL-4. IL-10, IL-13), chemokines (MCP-1, MIP-1α, RANTES), and macrophage colony-stimulating factor did not alter CD4 expression in primary macrophages, granulocyte-monocyte colony-stimulating factor and the prototypal Th1 cytokine interferon-gamma (IFN-γ) modulated surface CD4 expression only after prolonged treatment (5 days). Our results show that LPS. TNF-α and IL-1β selectively down-regulate CD4 expression in primary human macrophages, and that decreased CD4 expression induced by LPS results from endogenous secretion of TNF-α and IL-1β by the macrophages.
T cell activation byTheileria annulata-infected macrophages correlates with cytokine production
Authors: Brown D J , Campbell J D M , Russell G C , Hopkins J , Glass E J 
Published: July 2010

SUMMARYA major feature of the pathology induced by Theileria annulata is acute lymphocytic proliferation, and this study investigates the mechanisms underlying the intrinsic ability of T. annulata-infected monocytes to induce naive autologous T cells to proliferate. Different T. annulata-infected clones expressed different but constant levels of MHC class II, varying from &lt; 1.0 × 105 to 1.5 × 106 molecules/cell, as measured by saturation binding. However, no correlation was found between the level of MHC class II expression and levels of induced T cell proliferation. Theileria anmulata infected cell lines and clones were assayed for cytokine mRNA expression by reverse transcriptionpolymerase chain reaction (RT-PCR). The infected cells assayed produced mRNA specific forIL-lα, IL-1β, lL-6, IL-10 and tumour necrosis factor-alpha (TNF-a). but not IL-2 or lL-4. One clone (clone G)did not produce mRNA for TNF-α. The degree of T cell proliferation induced by infected cells was directly correlated with the amount of mRNA produced for the T cell stimulatory cytokines IL-lα and IL-6, as assessed by a semiquantitative technique. In contrast, cells infected with the related parasite T. parva produced mRNA for IL-lα, IL-2, IL-4, IL-10 and interferon-gamma (IFN-γ). Since T. parva-infected cells also induce naive autologous T cell proliferation, it seems likely that the production of lL-1α by cells infected with either parasite is a major signal for the induction of non-specific T cell proliferation.
Phenotypic characterization of two cell populations involved in the acquisition of suppressor activity by cultured spleen cells fromMycobacterium lepraemurium-infected mice
Authors: Gosselin D , Turcotte R , Lemieux S 
Published: July 2010

SUMMARYThe impairment of cellular immunity in mice infected with Mycobacterium lepraemurium was shown to correlate with the development of suppressor cells. We have previously reported that before suppressor activity is detectable in freshly harvested cell suspensions, suppressor cell precursors accumulate in the spleen of infected mice. Upon overnight culture in the presence of a regulatory cell subset, these precursor cells acquire the capacity to impair the concanavalin A (Con A)-induced proliferation of normal spleen cells. The purpose of this study was to determine the phenotype of the cells involved in this phenomenon. This was done by following the development of suppressor activity in spleen cell suspensions depleted of defined cell subsets of the adherent or the non-adherent cell fractions with selected MoAbs and immunomagnetic beads or by in vivo treatment. Our results indicate that the acquisition of suppressor activity requires the interaction of Ia+CD11b+FcγR+IgG- asialo GMI- adherent cells with Thyl 1-CD4-CD8-lgG- Ia- asialo GMl -FcγR+CD1 lb+ non-adherent cells. It is also shown that the development of suppressor activity is impaired by preventing cell-cell contact between these two cell subsets through coculture in ‘Transwell chambers’. These observations support the conclusion that the in vitro acquisition of suppressor activity is a consequence of the maturation of suppressor cell precursors of the monocytic lineage induced by a receptor-ligand type interaction with a non-adherent cell subset that is clearly distinct from mature T, B and natural killer (NK) cells.
Serum soluble markers in the evaluation of treatment in human visceral leishmaniasis
Authors: Schriefer A , Barral A , Carvalho E M , Barral-Netto M 
Published: July 2010

SUMMARYVisceral leishmaniasis (VL) has a fatal course if not properly treated. Recovery from VL is linked to cellular immune response. Unresponsiveness to antimonial therapy reinforces the importance of determining parameters for treatment assessment. We analysed the pre- and post-treatment serum levels of solubleCD4(sCD4).sCD8. SI L-2R, soluble intercellular adhesion molecule-1 (sICAM-1) and neopterin in groups of VL patients either responsive or not to standard antimonial therapy. Pretreatment serum levels of all markers except for sICAM-1 were significantly higher in VL patients than in healthy subjects from the same area (P &lt; 0 05). sICAM-1 levels were similar in healthy controls and in VL patients refractory to antimonial therapy (p = 0 25), but significantly higher in patients responsive to treatment (p = 0.02). The comparison of pre- and post-treatment concentrations showed that all markers, except sCD4 and sICAM-1, presented a significant fall (p &lt; 0. 05) in patients responsive to antimonial therapy. However, only neopterin presented with levels compatible with those of healthy subjects at the end of treatment (p = 0. 30). In refractory patients sICAM-1 presented with post-treatment levels significantly higher than the pretreatment determinations (p = 0.03). while sCD4 experienced a significant drop (p = 0. 01) All markers displayed clearly distinct behaviour according to the patient's response to therapy. This makes all soluble molecules studied suitable for use as indicators of antimonial therapy response. Additionally the comparison of pretreatment levels of the markers between responders and refractory patients to antimonial therapy showed that serum concentrations of sIL-2R and sICAM-1 significantly differed among these two groups (p=0.02 in each case), suggesting that they may be used in future as predictors of antimonial therapy response.
Changes in the phenotype of monocytes/macrophages and expression of cytokine mRNA in peripheral blood and synovial fluid of patients with rheumatoid arthritis
Authors: Highton J , Carlisle B , Palmer D G 
Published: July 2010

SUMMARYData from a previous study suggested that peripheral blood monocytes in patients with rheumatoid arthritis (RA) may be activated. Therefore, in this study we sought further evidence of ‘presynovial’ activation of monocytes. Our results show that phenotypic changes are demonstrable in peripheral blood monocytes in patients with RA, including increased expression of CR3 (CDllb/CD18) and FcRI (CD64). However, changes are most extensive in synovial monocytes/macrophages and especially for HLA-DR and intercellular adhesion molecule-1 (ICAM-1) (CD54). We conclude that monocyte/macrophage activation is most evident within the joint, and that ‘presynovial’ changes occur but are of limited extent.
Differential effects of methotrexate and liposomally conjugated methotrexate in rat adjuvant-induced arthritis
Authors: Williams A S , Camilleri J P , Amos N , Williams B D 
Published: July 2010

SUMMARYIn this study we evaluated the comparative efficacy of free and liposomally conjugated methotrexate on both disease indtiction and suppression of acute inflammation in rat adjuvant-induced arthritis. Rats were given either empty liposomes (E-LIPO), free methotrexate (MTX) or the liposomally conjugated methotrexate (MTX-LIPO) at a dose of 100/μg/day for 7 consecutive days by the intravenous route. When MTX treatment was initiated on the day of arthritis induction the drug suppressed bul did not abolish the development of joint inflammation. Free MTX had no significant anti-inliammatory effect upon an established arthritis when dosing was commenced on day 11 post-adjuvant induction. Conversely, MTX-LIPO did not affect the progression of the arthritis when dosing was started on day 0, but exerted a significant anti-inflammatory effect on an established arthritis. MTX-LIPO treatment was significantly less haematotoxic than free MTX.
Comparison of activation marker and TCR Vβ gene product expression by CD4+ and CD8+ T cells in peripheral blood and lymph nodes from HIV-infected patients
Authors: Ramzaoui S , Jouen-Beades F , Michot F , Borsa-Lebas F , Humbert G , Tron F 
Published: July 2010

SUMMARY
Since lymphoid organs constitute the site of active and progressive HIV disease, analysis of their lymphocytes may provide more accurate information on T cell abnormalities than that obtained from studying peripheral blood lymphocytes. The objective of this study was to compare the expressions of activation markers and T cell receptor (TCR) Vβ gene products by CD4+ and CD8+ T cells in lymph nodes (LN) and peripheral blood (PB) from healthy individuals and asymptomatic HIV-infected patients to determine whether anomalies that could be identified at the HIV replication site could support the hypothesis of T cell activation by HIV-encoded antigens or superantigens. CD4+ and CD8+ T cells in paired LN and PB obtained from six healthy controls and five asymptomatic HIV-infected individuals were analysed by flow cytometry, using anti-CD38, anti-HLA-DR and 13 anti-Vβ MoAbs that cover, approximately, 45% of the T cell repertoire. Analysis of T cell activation marker expression indicated that the percentages of CD4+ and CD8+ T cells bearing CD38 or CD38 and HLA-DR molecules were higher in patients than in controls and, in patients, higher in LN than in PB. Comparison between the Vβ repertoires of CD4+ and CD8+ T cells in LN and PB showed that, in each healthy individual, a limited number of Vβ families expressed by CD4+ or CDS+ T cells had different repartition in LN and PB, whereas in each HIV+ patient, more Vβ families exhibited different distributions and these differences recurred among certain Vβ segments, such as Vβ5.3 and Vβ21 in the CD4+ T cell population and Vβ5.2/5.3, Vβ12 and Vβ12 in the CD8+ T cell population. Taken together, these data argue for a skewed TCR repertoire in HIV infection and sustained activation of T cells by HIV-encoded antigens at the site of HIV replication, and further demonstrate that a high proportion of CD4+ T cells are in an activation state that may, indirectly, participate in their functional abnormalities.
Theileria annulatainduces abberrant T cell activationin vitroandin vivo
Authors: Campbell J D M , Howie S E M , Odling K A , Glass E J 
Published: July 2010

SUMMARYThe protozoan parasite of cattle, Theileria annulata, causes a severe lymphoproliferative disease, developing initially in the draining lymph node, which is often fatal in naive animals. Infection of macrophages with T. annulata leads to an augmentation of their antigen-presenting capability in vitro and infected cells can induce proliferation of autologous resting T cells from naive animals. This inappropriate activation of T cells may play an important role in the failure of the host to mount an effective immune response in vivo. To investigate this hypothesis we characterized further the response of T cells from naive cattle to infected cells in vitro, and also examined the development of the immune response in lymph nodes draining the sites of T. annulata infection. Both CD4+ and CD8+ T cells from naive peripheral blood mononuclear cells (PBMC) were induced to proliferate and express the activation markers IL-2R and MHC class II when cultured with infected cells. This effect was seen in both ‘naive’ and ‘memory’ T cells, and was dependent upon contact with infected cells. In vitro, infected cells are therefore capable of activating T cells irrespective of their antigen specificity or memory status. In draining lymph nodes, although large numbers of IL-2R+ cells developed following infection, these activated cells were only associated with areas of parasite-induced proliferating cells, and subsequently disappeared from the node. Cells expressing IL-2R were not present in recognized sites for T cell development. Germinal centres were severely affected, losing T cell-dependent zones followed by a total destruction of morphology. T cell function is therefore severely disrupted within draining nodes. This study has shown that parasitized cells supply sufficient signals in vitro to activate T cells irrespective of specificity. T cells also are not stimulated in a conventional manner in vivo, and this may play an important role in preventing an effective immune response from being generated.