bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fine specificity of human T cell lines towards myelin basic protein peptides in southern italian multiple sclerosis patients
Authors: Montanaro D , Sanna V , Matarese G , Larby B B , Racioppi L , Carrieri P B , Bruno R , Davey N J , Zappacosta S , Fontana S 
Published: March 2003

SUMMARYWe studied the relationship between the HLA specificities associated with multiple sclerosis (MS) susceptibility in southern Italy and the reactivity of the human myelin basic protein (hMBP) immunogenic peptides 84–98 and 143–168, using short-term T-cell lines established from 9 MS patients and from 8 healthy individuals. In our population, DR15 was significantly associated with MS (34·9% in MS versus 13·7% in healthy controls, P &lt; 0·05). This result is in agreement with the association found in northern Europe, but not with data obtained in a population from the island of Sardinia (Italy). In MS patients the frequency of reactive T-cell lines (TCL), tested for fine specificity against the immunodominant hMBP peptides 84–98 and 143–168, was increased for the hMBP 143–168 peptide (P &lt; 0·05) but not for the 84–98 peptide. Although this reactivity was higher in DR15+ MS patients than in DR 15− MS patients, it seemed not to be associated with DR15 specificity in the MS population. Furthermore, there were no significant differences in frequency of reactive TCL to hMBP peptide 84–98 in DR15-positive or DR15-negative MS patients. Consequently, it appears that peptide 84–98, considered as a relevant autoantigen, is not implicated in the pathogenesis of MS in our population from southern Italy.
Polarized secretion of CXC chemokines by human intestinal epithelial cells in response toBacteroides fragilisenterotoxin: NF-κB plays a major role in the regulation of IL-8 expression
Authors: Kim J M , Oh Y K , Kim Y J , Oh H B , Cho Y J 
Published: March 2003

SummaryEnterotoxigenic B. fragilis, which produces a ∼20 kD heat-labile toxin (BFT), has been associated with diarrhoeal diseases and mucosal inflammation. To determine if epithelial cells can contribute to BFT-induced inflammation, we assessed the expression of CXC chemokines by BFT-stimulated human intestinal epithelial cells. BFT stimulation increased expression of the neutrophil chemoattractant and activators ENA-78, GRO-α, and IL-8. Up-regulated chemokine mRNA expression was paralleled by increased protein levels. Activation of the IL-8 and NF-κB transcriptional reporters was inhibited in cells cotransfected with the IκB kinase β and IkBα superrepressor plasmids. Whereas lactate dehydrogenase, which was used to monitor cell lysis, was released predominantly from the apical surface, CXC chemokines were predominantly secreted from the basolateral surface of BFT-treated epithelial cells. The basolateral secretion of CXC chemokines from BFT-stimulated colon epithelial cells suggests that these chemokines can contribute to the inflammatory cell infiltrate in the underlying intestinal mucosa.
Effect of oestrogen onMycobacterium aviumcomplex pulmonary infection in mice
Authors: Tsuyuguchi K , Suzuki K , Matsumoto H , Tanaka E , Amitani R , Kuze F 
Published: March 2003

SummaryThe purpose of the present study was to elucidate the role of oestrogen in the pathogenesis of Mycobacterium avium complex (MAC) pulmonary disease, which occurs most frequently in postmenopausal women. The study was carried out in a murine infectious model using ovariectomized DBA/2 female mice. Infection with MAC was established by intratracheal administration of bacilli. In some experiments, ovariectomized mice were treated with exogenous 17β-estradiol (E2). The number of bacilli in the lungs of infected mice which received ovariectomy was significantly larger than that in the lungs of sham-operated control mice, and treatment of ovariectomized mice with exogenous E2 restored the burden of bacilli to the same level as that in the sham-operated control mice. We next examined the effect of E2 in vitro using bone marrow-derived macrophages obtained from DBA/2 female mice. The macrophages showed bacteriostatic activity against MAC after treatment with interferon-gamma (IFN-γ) and this activity was further enhanced by the exogenous addition of E2 to the culture medium. In parallel with these findings, E2 augmented the production of reactive nitrogen intermediates (RNI) by macrophages pretreated with IFN-γ and stimulated with MAC, as shown by evaluating nitrite production and inducible nitric oxide synthase mRNA expression. These findings taken together suggest that absence of endogenous oestrogen appears to be responsible for the development of MAC pulmonary disease in this mouse model and that the enhancement by E2 of anti-MAC activity of murine macrophages induced through increased RNI production may play some role in resistance to MAC infection.
Gender-dependent specific immune response during chronic humanSchistosomiasis haematobia
Authors: Remoué F , To Van D , Schacht A-M , Picquet M , Garraud O , Vercruysse J , Ly A , Capron A , Riveau G 
Published: March 2003

SUMMARYThe cellular and humoral acquired immune responses to Schistosoma haematobium 28 kD gluthathione S-Transferase (Sh28GST) antigen were evaluated in a Senegalese population chronically infected with S. haematobium parasite. We show a gender-dependent immune response in adult individuals presenting similar intensities of infection. Indeed, the specific IgA response and production of TGF-β and IL-10 were found significantly higher in females compared to males. In addition, we showed that this profile was combined with a weak production of Th1-related cytokines (TNFα and IFNγ) and was associated with an absence of proliferation to the antigen. A significantly higher Nuclear Matrix Protein 41/7 secretion, an apoptosis marker, was specifically observed in mononuclear blood cell cultures of females suggesting that a specific cell death process was engaged in a gender-dependent manner. This specific profile could be associated with the so-called T helper type-3 (Th3) immune response specifically promoting the production of IgA and would be developed upon the down-regulation of the specific Type-1 response by a probable cell death mechanism. This gender-dependent immune regulation, which may be under the influence of nonimmunological factors like sexual hormones, may be related to the chronicity of the infection.
Molecular mapping of epitopes on melanocyte-specific protein Pmel17 which are recognized by autoantibodies in patients with vitiligo
Authors: Kemp E H , Waterman E A , Gawkrodger D J , Watson P F , Weetman A P 
Published: March 2003

SUMMARYPreviously, we reported the identification of Pmel17 autoantibodies in some patients with vitiligo. Here, we have determined the B cell epitopes on Pmel17 which are recognized by these autoantibodies. Deletion derivatives of Pmel17 cDNA were constructed using either subcloning of specific cDNA fragments or polymerase chain reaction amplification. Full-length Pmel17 cDNA and its truncated derivatives were then translated in vitro to produce [35S]-labelled proteins. The radiolabelled ligands were used subsequently in radiobinding assays to investigate the reactivity of sera from vitiligo patients. Two epitope regions were identified: one located at the C-terminal end of Pmel17 between amino acids 634–644 and one in a central region of the protein between amino acids 326–341. Computer analysis of the potential B cell epitopes on Pmel17 revealed that the epitope domain encompassing amino acids 326–341 was located in an area of the protein which was predicted to be highly antigenic. In contrast, the epitope identified at the C-terminal of Pmel17 (amino acids 634–644) was located in a region of the protein predicted to have low antigenicity. The amino acid sequences of the identified Pmel17 epitopes were compared to the amino acid sequences of the related melanogenic enzymes tyrosinase, tyrosinase-related protein-1 and tyrosinase-related protein-2. However, no sequence homology was found between either of the Pmel17 epitopes and the aforementioned proteins. This finding is consistent with our previous study in which we were unable to show the presence of Pmel17 antibodies which were cross-reactive with either tyrosinase, tyrosinase-related protein-1 or tyrosinase-related protein-2. It also suggests that the IgG response to Pmel17 is distinct from the antibody response to the other melanocyte-specific antigens.
Complete arrest from pro- to pre-B cells in a case of B cell-negative severe combined immunodeficiency (SCID) without recombinase activating gene (RAG) mutations
Authors: Agematsu K , Nagumo H , Hokibara S , Mori T , Wada T , Yachie A , Kanegane H , Miyawaki T , Sugita K , Karasuyama H , Komiyama A 
Published: March 2003

SUMMARYThe B-cell lineage in a patient with B-cell-negative severe combined immunodeficiency (SCID) was analysed by using antisurrogate light chain (SL) MoAbs. Peripheral CD3+ T cells and CD19+ B cells were absent in the patient. The common gamma (γc) chain was expressed normally on the patient's peripheral NK cells and his peripheral mononuclear cells did not possess any mutations in recombinase activating gene (RAG)-1, 2. Normal levels of expression of Ku70 and Ku80 protein were found by Western blot analysis. The patient did, however, display an increase in fibroblast sensitivity to irradiation. Furthermore, flow cytometric analyses of bone marrow cells showed that surface IgM and cytoplasmic µ positive cells were absent and that CD19+ B cells were composed of only CD34+ terminal deoxynucleotidyl transferase (TdT)+ SL+ pro-B cells. The complete arrest of pro- to pre-B cell development in the SCID patient's bone marrow suggests that some genes involved in V(D)J recombination, excepting the RAG gene, may play a causative role in the immunodeficiency.
Plasma cytokine response to surgical stress in schizophrenic patients
Authors: Kudoh A , Sakai T , Ishihara H , Matsuki A 
Published: March 2003

SummarySchizophrenic patients are reported to have immunological dysfunction, however, the immune response to surgery in schizophrenic patients remains unclear. We measured plasma interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α) before, during and after colectomy, hemicolectomy and sigmoidectomy in 25 chronic schizophrenic patients (Group S) and 25 control patients (Group C) using ELISA assays. We could find no significant difference in the baseline plasma concentrations of IL-6, IL-8 and TNF-α between Group S and Group C. Plasma IL-6 concentrations (32·1 (30·3) and 15·8 (9·6) pg/ml) in Group S at the end of the operation and 24 h after surgery were significantly lower than 76·9 (37·1) and 35·1 (21·5) pg/ml of Group C. Plasma IL-8 concentration (6·1 (2·8)) in Group S at the end of the operation was significantly lower than 8·7 (4·2) pg/ml of Group C. There were no significant changes in plasma TNF-α concentration throughout the study period in either group. Plasma cortisol concentrations of schizophrenic patients during surgery were significantly lower than those of control patients. The plasma IL-6 concentrations correlated with plasma cortisol concentrations in either group. We conclude that proinflammatory cytokine response to abdominal surgery is inhibited in schizophrenic patients.
Novel immunosuppressive effect of FK506 by augmentation of T cell apoptosis
Authors: Hashimoto Y , Matsuoka N , Kawakami A , Tsuboi M , Nakashima T , Eguchi K , Tomioka T , Kanematsu T 
Published: March 2003

SummaryWe have recently reported the accumulation of oligoclonal activated T cells in the spontaneously developed autoimmune pancreatitis in aly/aly mouse. In this study, we examined the effects of FK506 in this mouse model in preventing autoimmune pancreatitis and investigated its action on calcium signalling apoptosis of alymphoplasia (aly) lymphocytes in vitro. Mice were treated with FK506 from 8 to 25 weeks of age. At the age of 15 weeks, minimal mononuclear cell infiltration was observed in the pancreas in both the FK506 treated group and the control group. Furthermore, a marked cell infiltration associated with destruction of acini and partial fatty changes were observed in 25-week-old control mice. In contrast, FK506 treated mice showed almost no tissue destruction or mononuclear cell infiltration at the age of 25 weeks. Furthermore, at 15 weeks of age, most mononuclear cells in FK506-treated mice were TUNEL positive, whereas only a few were positive in control mice. This augmentation of T cell apoptosis by FK506 was confirmed using naive splenocytes activated by PMA and ionomycin in vitro. Finally, a suppressive effect of FK506 on Bcl-2 production but not on Bax production was confirmed by Western blotting. This unique effect of FK506 on the augmentation of T cell apoptosis is probably one of the mechanisms explaining its beneficial effect on aly autoimmune pancreatitis.
Changes in thymic function in HIV-positive patients treated with highly active antiretroviral therapy and interleukin-2
Authors: De Paoli P , Bortolin M T , Zanussi S , Monzoni A , Pratesi C , Giacca M 
Published: March 2003

SummaryDespite its potent antiviral activity, highly active antiretroviral therapy (HAART) only exerts a marginal effect on CD4+ T-cell regeneration in HIV-infected subjects. Combination therapies aimed at boosting T-cell activity and maturation may provide an important contribution to the restoration of immune function. Here, we report the results obtained by a two-year follow-up of a cohort of HIV-infected patients treated with a combination of HAART and interleukin-2 (IL-2). In these patients, in addition to a series of quantitative virological and immunological parameters, we investigated T-cell regeneration by an immunophenotypic assay monitoring CD4+ naïve T cells, and by analysis of thymic function, through the quantification of the excision DNA products of T-cell receptor rearrangement (TRECs) in lymphocytes. Compared with HAART alone, we found that the IL-2 combination therapy was equally effective in reducing the levels of viremia and marginally more effective in decreasing proviral DNA load. Strikingly, the IL-2 combination produced a marked increase in the number of CD4+ T cells bearing a naïve phenotype (CD45RA+, CD62L+), which was apparent for over 96 weeks after therapy. To assess whether these cells were the product of improved T-cell generation, we exploited a competitive quantitative molecular assay to quantify TRECs in peripheral blood lymphocytes. Surprisingly, we found that the levels of these molecules were unchanged in these patients. These findings indicate that improved thymic function does not account for the early rise of CD4 naïve cells in HIV-positive patients treated with IL-2, and suggest that alternative mechanisms of T-cell maturation and differentiation are responsible for this event.
Granule-dependent cytolysis ofMycobacterium tuberculosis-infected macrophages by humanγδ+ T cells has no effect on intracellular mycobacterial viability
Authors: Passmore J S , Glashoff R H , Lukey P T , Ress S R 
Published: March 2003

SummaryOne of the most important effector functions of activated γδ+ T cells in tuberculosis is their strong cytolytic activity against a variety of target cells, including M. tuberculosis-infected macrophages. In the present study, we investigated the relationship between the mechanism of cytolysis utilized by γδ+ CTL and intracellular M. tuberculosis survival using a panel of cytolytic human M. tuberculosis-specific γδ+ CTL clones. Cytolysis mediated by the γδ+ T-cell clones was found to be Ca2+-dependent, sensitive to Cyclosporin A, and was completely abrogated following Sr2+-induced de-granulation of the γδ+ T cell effectors. These data demonstrate that γδ+ T-cell-mediated cytoxicity was mediated via the granule exocytosis/perforin pathway. Despite significant cytolytic activity against mycobacteria infected U937 cells, the γδ+ CTL clones had no impact on the survival of intracellular M. tuberculosis.
Heightened ability of monocytes from sarcoidosis patients to form multi-nucleated giant cellsin vitroby supernatants of concanavalin A-stimulated mononuclear cells
Authors: Mizuno K , Okamoto H , Horio T 
Published: March 2003

SummaryThe main immunocompetent cells in sarcoidal lesions are epithelioid cells and multi-nucleated giant cells (MGC), both of which are derived from monocyte-macrophage lineage cells. To understand further the relevance of monocytes in sarcoidosis, we examined in vitro MGC formation using monocytes from sarcoidosis patients, patients with other granulomatous diseases (OGD) and healthy control subjects. The supernatant of concanavalin A-stimulated peripheral blood mononuclear cells (conditioned medium) generated Langhans type-MGC and foreign body type-MGC from monocytes. Conditioned medium from any three groups had the same ability to form MGC from normal monocytes. On the other hand, MGC were more highly formed using monocytes from sarcoidosis patients than from other groups. When macrophages induced by treatment of monocytes with macrophage colony-stimulating factor (M-CSF) were used, the rate of MGC formation in sarcoidosis patients was about threefold or fourfold as much as that in OGD patients or healthy controls, respectively. Oxidized ATP inhibited MGC formation in all groups. The susceptibility of monocytes cultured in conditioned medium for 24 h to 2′- and 3′-o-(4-benzoyl-benzoyl)ATP-mediated cytolysis was significantly higher in sarcoidosis patients than other groups. These findings suggest that the ability of monocytes to form MGC through P2×7 receptors is enhanced in sarcoidosis patients.
The effects of iron deficiency on lymphocyte cytokine production and activation: preservation of hepatic iron but not at all cost
Authors: Jason J , Archibald L K , Nwanyanwu O C , Bell M , Jensen R J , Gunter E , Buchanan I , Larned J , Kazembe P N , Dobbie H , Jarvis W R 
Published: March 2003

SummaryWorldwide, over 40% of children have iron deficiency anaemia, frequently associated with infections. Certain cytokines are involved in both immune activation/response to infection and iron transport/metabolism. We therefore assessed the relations among iron deficiency, cytokine production and lymphocyte activation markers in 142 hospitalized Malawian children. We examined peripheral blood lymphocyte antigens/cytokine production using four- colour flow cytometry and serum transferrin receptor (TfR) levels, an inverse measure of iron status unaffected by acute illness or infection, with an enzyme-linked immunosorbent assay. Wilcoxon rank sum tests and logistic regression analyses (LRA) were performed. Iron deficiency (TfR ≥ 10 μg/ml) versus TfR &lt; 10 μg/ml, was associated with higher percentages of lymphocytes producing: (a) induced or spontaneous IL-6 (medians: induced, 15·9% for iron-deficient children versus 8·8% for iron-replete children, P= 0·002; spontaneous, 24·4% versus 13·0%, P &lt; 0·001) and (b) induced IFN-γ (medians:18·4% versus 12·4%, P= 0·006). The percentages of CD8+ T cells spontaneously producing IL-6 and of all lymphocytes producing induced TNF-α and IFN-γ in the same cell had the strongest relationships to iron deficiency (b = + 0·0211, P= 0·005 and b =+ 0·1158, P= 0·012, respectively, LRA) and were also positively related to the co-expression of the T cell activation markers HLA DR and CD38. Severe iron deficiency (TfR ≥ 30 μg/ml) was associated with the percentage of lymphocytes producing induced IL-4 (medians: 0·5% versus 1·6%, P &lt; 0·010).The cytokine patterns associated with iron deficiency in our study would preserve iron stores but also preferentially retain the activation capabilities of T cells, albeit not necessarily other immune cells, until a critical level of iron depletion is reached.
Activated macrophages for treating skin ulceration: gene expression in human monocytes after hypo-osmotic shock
Authors: FRENKEL O , SHANI E , BEN-BASSAT I , BROK-SIMONI F , ROZENFELD-GRANOT G , KAJAKARO G , RECHAVI G , AMARIGLIO N , SHINAR E , DANON D 
Published: March 2003

SUMMARY
Macrophages play a major role in almost all stages of the complex process of wound healing. It has been previously shown that the incorporation of a hypo-osmotic shock step, in the process of monocyte-concentrate preparation from a blood unit, induces monocyte/macrophage activation. As the macrophages are produced using a unique, closed and sterile system, they are suitable for local application on ulcers in elderly and paraplegic patients. Enhanced phagocytosis by the activated cells, as well as increased secretion of cytokines such as IL-1, IL-6, were detected in a recent study which are in accord with the very encouraging clinical results. In the present study, we used DNA microarrays to analyse the differential gene expressions of the hypo-osmotic shock-activated monocytes/macrophages and compare them to non-treated cells. Of the genes that exhibited differences of expression in the activated cell population, 94% (68/72) displayed increased activity. The mRNA levels of 43/68 of these genes (63%) were found to be 1·5-fold or higher (1·5–7·98) in the activated macrophages cell population as compared to the non-treated cells. Only four genes were found to have lower mRNA levels in the activated cells, with ratios of expression of 0·62–0·8, which may suggest that the changes are insignificant. A significant number of the genes that showed increased levels of expression is known to be directly involved in macrophage function and wound healing. This may correlate with the increased secretion of different cytokines by the activated macrophages depicted previously. Other groups of genes expressed are known to be involved in important pathways such as neuronal growth and function, developmental defects and cancer. The hypo-osmotic shock induces a gene expression profile of cytokines and receptors in the activated cells. These may evoke potential abilities to produce a variety of protein products needed in the wound healing process and may bring to light possibilities for other therapeutic applications of these cells.
IFN-gamma and IL-12 but not IL-10 are required for local tumour surveillance in a syngeneic model of orthotopic bladder cancer
Authors: Riemensberger J , Böhle A , Brandau S 
Published: March 2003

SummaryIn recent studies, a crucial role for IFN-γ in immunosurveillance of tumours and in IL-12 immunotherapy has been suggested. Nevertheless, little is known about the relevance of IFN-γ and IL-12 for tumour surveillance in noncytokine immunotherapy. Adjuvant immunotherapy with viable BCG (Bacillus Calmette–Guérin) is considered to be the most powerful clinical treatment regimen of bladder cancer and is known to induce a variety of proinflammatory cytokines. Consequently, we analysed the antitumour response of IFN-γ knockout (KO), IL-12 KO and IL-10 KO mice in the absence and presence of BCG immunotherapy in a syngeneic orthotopic model of bladder cancer. IFN-γ KO and IL-12 KO mice died much earlier and by far smaller tumour inocula compared to wildtype mice, while this intrinsic antitumour response was not altered in IL-10 KO mice. BCG immunotherapy was effective in wildtype mice, but totally ineffective in IFN-γ KO and IL-12 KO mice. BCG induced a massive local immune response in the bladder of treated animals. This response was markedly increased in IL-10 KO mice, which coincides with increased therapeutic efficacy in this mouse strain compared with wildtype mice. Our data establish a crucial role for a Th1 type immune response in the intrinsic and immunotherapeutic control of local orthotopic bladder cancer.