bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell proliferation, MHC class II restriction and cytokine products of gliadin-stimulated peripheral blood mononuclear cells (PBMC)
Authors: O'keeffe J , Mills K , Jackson J , Feighery C 
Published: March 2003

SUMMARYThe immune response of PBMC to gliadin was investigated in patients with coeliac disease (CoD) by examining proliferation, MHC restriction and cytokine production. Gliadin induced low levels of proliferation in 63% of eight untreated patients, 32% of 28 treated patients and 35% of 31 healthy control subjects. In MHC restriction studies, the proliferative response to gliadin was inhibited (range 47–98% inhibition) in the presence of a MoAb to HLA-DR in each of three coeliac and three control donors studied. Using flow cytometry, increased expression of activation markers (HLA-DR and IL-2R) was demonstrated on gliadin-stimulated T cells from four of nine coeliac patients and three of seven healthy control donors. Cytokines were studied in culture supernatants using ELISA. Gliadin was a potent inducer of IL-6 and IL-10 in 100% of coeliac patients and controls, whereas IL-4 was not produced in either subject group. Gliadin induced IL-2 production in 40% of untreated patients, 42% of treated patients and 35% of healthy control donors. Interferon-gamma (IFN-γ) in gliadin-stimulated cultures was found only in coeliac patients, observed in 33% of untreated patients and 25% of treated patients. Spontaneous secretion of both IL-2 and IFN-γ was found more frequently in patients with untreated disease (87% of cases versus 21% of controls for IFN-γ and 40% versus 0% for IL-2). These results suggest, as manifest by IFN-γ production, that gliadin stimulates a Th1/Th0-like response in coeliac patients and a Th0-like response in healthy controls.
Suppressive effect of Chinese medicinal herb,Acanthopanax gracilistylus, extract on human lymphocytesin vitro
Authors: Shan B E , Yoshita Y , Sugiura T , Yamashita U 
Published: March 2003

SUMMARYWe studied the effect of a Chinese medicinal herb, Acanthopanax gracilistylus, extract (AGE), on human lymphocytes in vitro. AGE markedly suppressed the proliferative responses of human peripheral blood lymphocytes stimulated with mitogens concanavalin A (Con A) and Staphylococcus aureus Cowan I (SAC). Both T cell and B cell activities—production of interferon-gamma and immunoglobulin—were suppressed by AGE. The mechanism of AGE-induced suppression of lymphocytes is to arrest the cell cycle at the G0/G1 stage without a direct cytotoxic effect. AGE also suppressed the alloantigen-specific cytotoxic T lymphocyte response. However, natural killer cell activity was less sensitive to the suppressive activity of AGE. In contrast, AGE markedly enhanced monocyte function to produce cytokines. These activities of AGE were associated with a 60-kD protein which was sensitive to treatment with pronase E, but not with NaIO4. These results suggest that AGE has an immunomodulating activity on human lymphocytes and its properties could be clinically applied in the treatment of several diseases such as autoimmune and allergic diseases.
A lack of evidence for down-modulation of CD3ζ expression in colorectal carcinoma and pregnancy using multiple detection methods
Authors: Deakin A M , Singh K , Crowe J S , Ellis J H , Dalgleish A , Leicester R J , Finlayson C J , Miles W F A , Life P F 
Published: March 2003

SUMMARYLoss of the T cell receptor-associated CD3 ζ chain has been proposed as a possible mechanism of the acquired immunosuppression in both tumour-bearing hosts, and in symptomatic patients with HIV infection. However, other reports suggest that the ζ-chain loss may in part be caused by protease activity of contaminating phagocytes ex vivo. Using flow cytometry and Western blot analysis on highly purified T cells, and ensuring adequate addition of protease inhibitors, we have studied the expression of CD3ζ on peripheral blood T cells from patients with colorectal carcinoma, and compared these with normal controls, and pregnant donors, as a further example of an immunocompromised state. Immunohistochemistry was performed on tumour sections from patients with colorectal carcinoma to measure CD3ζ expression in tumour infiltrating T cells, and compared with normal mucosa and tonsil. Using these three approaches, our data provide no evidence for downregulation of CD3ζ chain expression either in colorectal carcinoma or pregnancy and suggest that this explanation is unlikely to fully account for the reduced T cell function associated with these conditions in all patients.
Apoptosis of CD4+ T cells occurs in experimental autoimmune anterior uveitis (EAAU)
Authors: Yu H G , Chung H , Lee W J 
Published: March 2003

SUMMARYTo investigate the spontaneous turning off mechanism of endogenous uveitis, EAAU was induced in Lewis rats. Immunohistochemical and terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) stains revealed that CD4+ T cells were predominant in the uveal tissue of EAAU and that the apoptosis of these cells had occurred and progressed throughout the inflammatory period in EAAU eyes. The immunohistochemistry and in situ hybridization for Fas ligand (FasL) expression showed that the expression of Fas ligand was increased in the EAAU eyes compared with control eyes. These results suggest that the apoptosis of CD4+ T cells may play a key role in the spontaneous turning off mechanism of intra-ocular inflammation and that the induction of apoptosis may be mediated by the Fas–FasL system in EAAU.
Increased serum levels of solublel-selectin (CD62L) in patients with active systemic lupus erythematosus (SLE)
Authors: Font J , Pizcueta P , Ramos-Casals M , Cervera R , García-Carrasco M , Navarro M , Ingelmo M , Engel P 
Published: March 2003

SUMMARYThe adhesion molecule l-selectin (CD62L) mediates lymphocyte recirculation and leucocyte rolling on vascular endothelium at sites of inflammation. Serum levels of soluble l-selectin (sl-selectin) were measured in patients with SLE in order to relate these levels to clinical activity and immunological parameters. An ELISA was used to detect the soluble form of human l-selectin (CD62L) in 42 patients with SLE and in 33 healthy individuals. The mean ± s.e.m. values of sl-selectin were 1285 ± 121 ng/ml for patients with SLE and 986 ± 180 ng/ml for healthy blood donors, but there was no significant difference. When patients with active SLE were analysed, higher levels of circulating sl-selectin were found when compared with patients without activity (1497 ± 167 ng/ml versus 941 ± 150 ng/ml; P = 0.028). We found a significant correlation between the levels of sl-selectin and of dsDNA antibodies (r = 0.36, P = 0.044) and between levels of sl-selectin and SLE Disease Activity Index (SLEDAI) score (r = 0.42, P = 0.003). Patients with active SLE studied cross-sectionally showed significant elevations of sl-selectin (CD62L) compared with controls. Thus, the levels of this soluble adhesion molecule correlated with active disease and levels of anti-dsDNA antibodies.
Inhibition of Epstein–Barr virus (EBV)-specific CD8+ cytotoxic T lymphocyte (CTL) activity by soluble HLA class Iin vitro
Authors: Gansuvd B , Hagihara M , Munkhbat B , Kanai N , Morita N , Munkhtuvshin N , Chargui J , Kato S , Hotta T , Tsuji K 
Published: March 2003

SUMMARYIn the present study, the effects of soluble HLA (sHLA) class I molecules against EBV-specific CTL were examined. Two different sources of sHLA class I, either bioengineered spliced form of HLA-B7 (sB7) or natural production from EBV-transformed B cells (natural sHLA), were added during the induction of CTL or incubated with MHC-restricted CD8+ CTL, which were selected by immunobeads just before testing for their cytotoxic activity. Both sB7 and natural sHLA class I blocked the generation of CD8+ CTL and also inhibited the cytotoxic activity of established CTL in a dose-dependent manner. In both ways, natural sHLA class I was effective in 10-fold lower concentrations compared with sB7. The inhibitory effect did not require a sharing of the HLA allotypes between sHLA and the CTL. CTL, after being treated with sHLA, underwent apoptosis, which was considered here as the main mechanism.
The role of IL-12 in inflammatory activity of patients with rheumatoid arthritis (RA)
Authors: Kim W-U , Min S-Y , Cho M-L , Youn J , Min J-K , Lee S-H , Park S-H , Cho C-S , Kim H-Y 
Published: March 2003

SUMMARYThe aim of this study was to investigate the role of IL-12 in patients with RA. IL-12 (p70) and its associated cytokines were measured in sera and synovial fluid (SF) using an enzyme-linked immunosorbent method. Seven American College of Rheumatology (ACR) core set measures as well as IL-12 levels were sequentially monitored at the commencement and 4 months after treatment with a low-dose steroid and disease-modifying anti-rheumatic drugs (DMARDs). In sera, 64 (42.2%) of 152 RA patients had detectable concentrations of IL-12 (p70), whereas one (1.4%) of 69 osteoarthritis (OA) patients and five (10%) of 50 healthy controls had detectable IL-12 (P &lt; 0.001). The median level of circulating IL-12 was also higher in RA patients (P &lt; 0.001). In SF, the number of patients with detectable IL-12 and the median IL-12 levels were significantly higher in RA patients (n = 53) than in OA patients (n = 22). In paired samples (n = 53) of sera and SF from RA patients, IL-12 levels were higher in the SF than in sera (P &lt; 0.001). Patients with detectable IL-12 (n = 51) in sera had higher tender joint scores (P = 0.003), swollen joint scores (P &lt; 0.001) and C-reactive protein (CRP; P = 0.036), than those without (n = 55). Four months after treatment with DMARDs, the improved group showed a larger IL-12 decrease than the non-improved group (P = 0.017). The levels of IL-12 correlated positively with those of IL-2, interferon-gamma, IL-6, and tumour necrosis factor-alpha, but were correlated inversely with those of IL-10. Our results demonstrate that IL-12 levels reflect RA disease activity and that IL-12 is involved in the production of proinflammatory cytokines. An IL-12 blockade could be useful for the treatment of RA.
Pretreatment of mice with lipopolysaccharide (LPS) or IL-1β exerts dose-dependent opposite effects on Shiga toxin-2 lethality
Authors: Palermo M , Alves-Rosa F , Rubel C , Fernández G C , Fernández-Alonso G , Alberto F , Rivas M , Isturiz M 
Published: March 2003

SUMMARY
Haemolytic uraemic syndrome (HUS) has been closely associated with infection with a group of Shiga toxin-producing enterohaemorrhagic Eschericchia coli in young children. Shiga toxins (Stx) have been implicated as pathogenic agents of HUS by binding to the surface receptor of endothelial cells. LPS is a central product of the Gram-negative bacteria and several reports have documented that both LPS and Stx are important for disease development. In this study the reciprocal interactions between LPS and Stx2 are analysed in a mouse model. The results demonstrated that LPS was able to reduce or enhance Stx2 toxicity, depending on the dose and the timing of the injection. The involvement of the main early cytokines induced by LPS, tumour necrosis factor alpha (TNF-α) and IL-1β, in those LPS opposite effects on Stx2 toxicity was evaluated. Stx2 toxicity was enhanced by in vivo injection of murine TNF-α and low doses of murine IL-1β. However, at higher doses of IL-1β which induced corticosteroid increase in serum, Stx2 lethality was decreased. Considering that dexamethasone and IL-1β reproduce the LPS protective effects, it is suggested that endogenous corticosteroids secondary to the inflammatory response induced by LPS, mediate the protection against Stx2. It can be concluded that the fine equilibrium between proinflammatory and anti-inflammatory activities strongly influences Stx2 toxicity.
Changes in the cytokine profile of lupus-prone mice (NZB/NZW)F1 induced byPlasmodium chabaudiand their implications in the reversal of clinical symptoms
Authors: Sato M N , Minoprio P , Avrameas S , Ternynck T 
Published: March 2003

SUMMARYWe have previously observed that aged lupus-prone (NZB/NZW)Fl (BWF1) mice when infected with Plasmodium chabaudi show an improvement in their clinical lupus-like symptoms. In order to study the mechanisms involved in the long-lasting protective effect of the P. chabaudi infection in lupus-prone mice we analysed specific aspects of the cellular response, namely the profiles of cytokine mRNA expression and cytokine secretion levels in old BWF1 mice, in comparison with uninfected age-matched BWF1 mice and infected or uninfected BALB/c mice. Two months after infection, cells from BWF1 mice were stimulated with concanavalin A (Con A) and demonstrated a recovery of T cell responsiveness that reached the levels obtained with BALB/c cells. Old BWF1 mice showed high levels of interferon-gamma (IFN-γ) and IL-5 production and correspondingly low levels of IL-2 and IL-4 secretion before infection with P. chabaudi. Infection did not modify the IFN-γ levels of BWF1 T cells, whereas it considerably increased the secretion of the Th2-related cytokines IL-4, IL-5 and IL-10. In addition, only BWF1 T cells showed increased mRNA expression of tumour necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β). This counter-regulatory cytokine network of infected BWF1 mice may be involved in the improvement of their lupus symptoms. The results of our investigations using the complex model of P. chabaudi infection can be extended and, by using more restricted approaches, it may be possible to explain the multiple regulatory defects of lupus-prone mice.
Comparison of the suppressive effects of soluble CR1 and C5a receptor antagonist in acute arthritis induced in rats by blocking of CD59
Authors: Mizuno M , Nishikawa K , Morgan B P , Matsuo S 
Published: March 2003

SUMMARYWe investigated the effects of suppression of complement activation at C3 level and inhibition of C5a on acute synovitis in rats. Acute synovitis was induced in Wistar rats by intra-articular (i.a.) injection into one knee of 0.3 mg of MoAb 6D1 (anti-rat CD59 antibody). In the treatment groups, soluble CR1 (sCR1) or C5a receptor (C5aR) antagonist was administered intra-articularly or intravenously and effects on the course of the acute synovitis were monitored. Synovitis induced by 6D1 was characterized by joint swelling, thickening of synovial tissue, cellular infiltration and deposition of membrane attack complex (MAC) on the synovial surface. Neither inflammatory change nor MAC deposition was found in rats which received an i.a. injection of sCR1 to suppress complement activity in the joint. Intra-articular injection of sCR1 did not reduce plasma complement activity. Intravenous administration of sCR1 suppressed plasma complement activity but had no effect on the course of the arthritis and synovitis with MAC deposition was observed. Neither i.a. nor i.v. injection of C5aR antagonist had any suppressive effects on inflammatory change or MAC deposition in synovium. The data show that inflammatory change induced by 6D1 was mediated by local complement activation and was not accompanied by systemic complement activation. C5a generation was not responsible for the observed inflammation, suggesting that other complement activation products, possibly MAC, mediate the inflammatory change observed in this model of acute synovitis in rats.
Clinical significance of serum soluble IL-2R levels in patients with adult T cell leukaemia (ATL) and HTLV-1 carriers
Authors: Araki K , Harada K , Nakamoto K , Shiroma M , Miyakuni T 
Published: March 2003

SUMMARYThe levels of soluble IL-2Rα (sIL-2Rα) in serum were measured in HTLV-1 carriers and ATL patients in order to evaluate their possible correlation with clinical status. Mean sIL-2R levels in ATL patients were found to be 9704 U/ml for the acute/lymphoma type, 1961 U/ml for the chronic type and 788 U/ml for the smouldering type. The level for asymptomatic HTLV-1 carriers was 475 U/ml, and 165 U/ml for healthy young adult HTLV-1− controls. The serial measurement of sIL-2R in ATL patients, healthy HTLV-1 carriers, and HTLV-1 carriers with diseases other than ATL showed a good correlation between serum levels of sIL-2R and the pathophysiological status of disease. Furthermore, an increase in the sIL-2Rα level in serum indicated the exacerbation of HTLV-1 infection and autoimmune diseases. The measurement of sIL-2Rα levels is therefore a very useful parameter for determining disease status.
Thromboxane A2 (TXA2) receptor blockade suppresses monocyte chemoattractant protein-1 (MCP-1) expression by stimulated vascular endothelial cells
Authors: Ishizuka T , Sawada S , Sugama K , Kurita A 
Published: March 2003

SUMMARYIn a previous study, it was reported that stimulation with a TXA2 receptor agonist, U46619, augments the expression of adhesion molecules by human umbilical vein endothelial cells (HUVEC). In the present study we showed that U46619 augments the expression of MCP-1 in HUVEC, both at the protein and mRNA levels. Pretreatment with TXA2 receptor antagonists greatly diminishes the extent of tumour necrosis factor-alpha (TNF-α)-, platelet-activating factor (PAF)-, or U46619-induced mRNA accumulation and production of MCP-1. Protein kinase C (PKC) inhibitors diminish U46619-induced mRNA accumulation and production of MCP-1. NAC, which inhibits nuclear factor κB (NF-κB) activation and activating protein 1 (AP-1) binding activity, inhibits the expression of MCP-1 at the protein and mRNA levels. These results indicate that in HUVEC stimulation via the TXA2 receptors augments MCP-1 production by induction of the NF-κB and AP-1 binding activity through the PKC system.
Multiple sclerosis is associated with an imbalance between tumour necrosis factor-alpha (TNF-α)- and IL-10-secreting blood cells that is corrected by interferon-beta (IFN-β) treatment
Authors: Özenci V , Kouwenhoven M , Huang Y-M , Kivisäkk P , Link H 
Published: March 2003

SUMMARYThe up-regulated B cell responses detectable in cerebrospinal fluid (CSF) and the augmented myelin antigen-specific T cell responses observed in the CSF as well as systematically in patients with multiple sclerosis (MS) suggest the involvement of cytokines in disease development and perpetuation. Here we report on the parallel involvement of TNF-α, IL-6, IFN-γ and IL-10 in MS and controls, using enzyme-linked immunospot (ELISPOT) assays to detect and enumerate cytokine-secreting mononuclear cells (MNC) prepared from blood and, for IL-6 and IL-10, from CSF without in vitro stimulation. MS is associated with elevated levels of TNF-α-secreting blood MNC when compared with levels in groups of control patients with myasthenia gravis (MG) and other neurological diseases (OND) or healthy subjects. This elevation was confined to patients with untreated MS and not present in those examined during ongoing treatment with IFN-β. Untreated patients with MS had lower numbers of IL-10-secreting blood MNC compared with the three control groups. In patients undergoing treatment with IFN-β, numbers of IL-10-secreting cells were in the same range as in controls. Normalization of TNF-α from elevated, and of IL-10 from decreased levels could be one reason for the beneficial effects of IFN-β in MS, although it remains to be shown whether these changes reflect phenomena primarily involved in MS pathogenesis or secondary changes. In CSF, levels of IL-10-secreting cells were higher than in blood in both MS and OND, with no difference between these groups. Systemic aberrations of IL-6 and IFN-γ and of IL-6 in CSF in MS versus controls were only minor, irrespective of treatment with IFN-β.
Autoepitopes on autoantigen centromere protein-A (CENP-A) are restricted to the N-terminal region, which has no homology with histone H3
Authors: Muro Y , Azuma N , Onouchi H , Kunimatsu M , Tomita Y , Sasaki M , Sugimoto K 
Published: March 2003

SUMMARYAnti-centromere autoantibodies (ACA) are commonly found in the serum of patients with a limited type of scleroderma and other systemic autoimmune diseases. CENP-A is one of the major antigens against ACA and a histone H3-like protein. To analyse the autoantigenic epitopes of CENP-A, a series of truncated peptides of human CENP-A were expressed in Escherichia coli and immunoblotting analysis was performed with 91 ACA+ sera. Eighty sera (88%) with the ACA reacted to the 52-amino acids N-terminal region which is not homologous to H3, while no sera reacted to the C-terminus which has a sequence similarity with H3. Moreover, ELISA was also employed in this study using two synthetic peptides corresponding to the amino acid sequences 3–17 (peptide A) and 25–38 (peptide B). Peptides A and B were reactive to 78 (86%) and 79 (87%) of ACA, respectively. Core antigens of hepatitis B virus (HBV) and hepatitis C virus (HCV) have similar sequences to peptide A and/or peptide B, but three sera containing HBV without ACA and five sera containing HCV without ACA were found to be reactive to neither peptide. Centromere localization of CENP-A is dependent on the H3-like C-terminal domain which is not autoantigenic, while the antigenic N-terminal domain, which might play unidentified functional roles, should be an important region for the induction of ACA.
Possible role of L-selectin in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis
Authors: Kaseda M , Kadota J , Mukae H , Kawamoto S , Shukuwa T , Iwashita T , Matsubara Y , Ishimatsu Y , Yoshinaga M , Abe K , Kohno S 
Published: March 2003

SUMMARYA number of adhesion molecules participate in the recruitment of inflammatory cells to the site of inflammation, and selectins together with their ligands are important in the early transient adhesion phase. In this study, we evaluated the role of L-selectin in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis. We measured serum and bronchoalveolar lavage fluid (BALF) concentrations of soluble (s) L-selectin using an ELISA. Serum and BALF concentrations of s L-selectin were significantly elevated in patients with sarcoidosis compared with control healthy subjects and idiopathic pulmonary fibrosis (IPF) patients (P &lt; 0.05 and P &lt; 0.01, respectively). The lymphocyte surface marker was also examined in peripheral blood and BALF by flow cytometric analysis. The percentage of CD3+CD62L+ cells ( L-selectin-bearing T lymphocytes) was significantly lower in peripheral blood of sarcoidosis than in that of healthy subjects (P &lt; 0.01). In contrast, the percentage of CD3+CD62L− cells ( L-selectin-negative T lymphocytes) in BALF of patients with sarcoidosis was significantly higher than in healthy subjects (P &lt; 0.05) and IPF patients (P &lt; 0.01). Furthermore, there was a significant correlation between serum concentrations of s L-selectin and the number of L-selectin-negative T lymphocytes in BALF (r = 0.535, P &lt; 0.01). Our results suggest that L-selectin may be involved in T lymphocyte alveolitis in patients with active pulmonary sarcoidosis.