bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-MHC autoimmunity in Behçet’s disease: T cell responses to an HLA-B-derived peptide cross-reactive with retinal-S antigen in patients with uveitis
Authors: Kurhan-Yavuz S , Direskeneli H , Bozkurt N , Özyazgan Y , Bavbek T , Kazokoglu H , Eksioglu-Demiralp E , Wildner G , Diedrichs-Möhring M , Akoglu T 
Published: March 2003

SUMMARY
Immune response to retinal autoantigens plays a central role in the pathogenesis of uveitis. A synthetic peptide (B27PD) from a common sequence of various HLA-B molecules associated with uveitis, such as HLA-B27 and 51, which shares amino acid homologies with a retinal-S antigen (S-Ag)-derived peptide (PDSAg), was shown to be immunogenic in human and experimental uveitis in the rat. In this study we investigated T cell responses to B27PD and PDSAg in patients with Behçet’s disease and posterior uveitis (BD-posterior uveitis; n = 33) in comparison with non-Behçet anterior uveitis (AU, n = 14), Behçet’s patients without uveitis (BD, n = 15) and healthy controls (HC, n = 32) in a 6-day proliferation assay. Patients with BD and posterior uveitis had significantly higher responses (stimulation index (SI) 2·8 ± 1·3) than those with AU (SI 1·5 ± 0·4), BD without uveitis (SI 1·1 ± 0·4) and HC (SI 1·1 ± 0·6) for B27PD (P &lt; 0·0001). Responses to PDSAg were also higher in BD with posterior uveitis patients (SI 3·3 ± 1·6) than AU (SI 1·5 ± 0·4), BD without uveitis (SI 1·2 ± 0·3) and HC (SI 1·1 ± 0·6) (P &lt; 0·0001). A significant correlation between the responses to PDSAg and B27PD (r = 0·56, P &lt; 0·001) was observed. Elevated levels of IL-2 and tumour necrosis factor-alpha were also observed in culture supernatants obtained from peripheral blood mononuclear cells after stimulation with the peptides, but no correlation was found between the proliferative responses and cytokine levels. These results suggest that cellular immunity to cross-reactive HLA-B and S-Ag-derived peptides might play a role in the pathogenesis of posterior uveitis in BD.
The proportion of circulatingγδT cells increases after the first week of onset of tularaemia and remains elevated for more than a year
Authors: Kroca M , Tärnvik A , Sjöstedt A 
Published: March 2003

SUMMARYIn various human intracellular bacterial diseases, an increase of the proportion of circulating Vγ9Vδ2 T cells has been observed. The prevalence of the finding among infected subjects and the time course of the elevation remain to be investigated. In the present study, comprising blood samples from a large number of cases of ulceroglandular tularaemia, the percentage of Vγ9Vδ2 T cells within the first week of onset of disease (5·3 ± 0·7% (mean ± s.e.m.)) did not differ from that of control subjects (5·3 ± 0·8%). Thereafter, percentages increased rapidly and within the interval of 8–40 days mean levels were &gt; 20% (P &lt; 0·001). Of 45 individuals sampled within 3 months of onset, 42 showed a percentage of Vγ9Vδ2 T cells of &gt; 10%. Significantly increased levels were still recorded at 18 months (13·8 ± 2·4%; P &lt; 0·05) but not at 24 months (10·2 ± 2·1%; P &gt; 0·10). Thus, a consistent increase of circulating Vγ9Vδ2 T cells was demonstrated in tularaemia. The initial delay and the prolonged course of elevation may suggest a role in immunoregulation and/or immunological memory. Furthermore, the percentage of γδ T cells expressing tumour necrosis factor-alpha in response to phorbol myristate acetate was decreased during the first week and up to 40 days after onset, possibly reflecting the modulation of an inflammatory response.
Elevated humoral immune response to heat shock protein 60 (hsp60) family in periodontitis patients
Authors: Tabeta K , Yamazaki K , Hotokezaka H , Yoshie H , Hara K 
Published: March 2003

SUMMARYThe presence of antibodies to the 60-kD human and Porphyromonas gingivalis GroEL hsp60 in the sera and inflamed gingival tissues of periodontitis patients was examined. In order to obtain the antigens, recombinant plasmids carrying human hsp60 and P. gingivalis GroEL genes were constructed and expressed as histidine-tagged recombinant proteins. Immunoreactivities of these proteins were confirmed by MoAbs specific to mammalian hsp60 and cross-reactive with both mammalian and bacterial hsp60. Western blot analysis clearly demonstrated that the number of periodontitis patients showing a positive response to P. gingivalis GroEL was higher than the number of periodontally healthy subjects. Furthermore, anti-P. gingivalis GroEL antibody was detected in all samples of gingival tissue extracts. For human hsp60, a higher frequency of seropositivity was found in the periodontitis patients than in the healthy subjects. In addition, the periodontitis patients demonstrated stronger reactivity compared with the healthy subjects. Quantitative analysis of serum antibodies by ELISA also demonstrated that the levels of antibodies in the sera of patients were significantly higher than those of control subjects. In the gingival tissue extracts, seven out of 10 patients demonstrated a positive response to human hsp60 and tso of these demonstrated strong positivity. Affinity-purified serum antibodies to human hsp60 and P. gingivalis GroEL from selected patients reacted with P. gingivalis GroEL and human hsp60, respectively, suggesting cross-reactivity of antibodies. These results suggest that molecular mimicry between GroEL of the periodontopathic bacterium P. gingivalis and autologous human hsp60 may play some role in immune mechanisms in periodontitis.
Intra-articular IL-10 gene transfer regulates the expression of collagen-induced arthritis (CIA) in the knee and ipsilateral paw
Authors: Lubberts E , Joosten L A B , Van Den Bersselaar L , Helsen M M A , Bakker A C , Xing Z , Richards C D , Van Den Berg W B 
Published: March 2003

SUMMARYWe studied the effects of local IL-10 application, introduced by a recombinant human type 5 adenovirus vector, in the mouse knee joint during the early phase of CIA. One intra-articular injection with the IL-10-expressing virus (Ad5E1mIL-10) caused substantial over-expression of IL-10 in the mouse knee joint, using virus dosages which did not induce distracting inflammation. High expression of IL-10 was noted for a few days, being maximal at day 1. One intra-articular injection of Ad5E1mIL-10 in the knee joints of collagen type II (CII)-immunized mice, before onset of CIA was noted, reduced the incidence of collagen arthritis in that knee. Of high interest, the protective effect of local IL-10 expression by Ad5E1mIL-10 was not restricted to the knee joint alone. The arthritis incidence in the ipsilateral paw was highly suppressed. In contrast, local IL-10 over-expression was not effective when treatment was started after onset of CIA. Further analysis in the acute streptococcal cell wall-induced arthritis model revealed that local IL-10 over-expression markedly suppressed the production of tumour necrosis factor-alpha (TNF-α) and IL-1α, but had no significant effect on IL-1β and IL-12 production in the inflamed synovium. These data indicate that local over-expression of IL-10 in the knee joint of mice regulates the expression of collagen arthritis, probably through down-regulation of TNF-α.
IVIG-bound IgG and IgM cloned by phage display from a healthy individual reveal the same restricted germ-line gene origin as in autoimmune thrombocytopenia
Authors: Hoffmann M , Uttenreuther-Fischer M M , Lerch H , Gaedicke G , Fischer P 
Published: March 2003

SUMMARYIntravenous immunoglobulin preparations (IVIG) have shown positive effects in the treatment of immune defects and autoimmune diseases. It is not clear how IVIG interacts with the components of the immune system. To investigate this, we cloned previously a large number of phage displayed IgG Fab fragments derived from three patients with autoimmune thrombocytopenia (AITP) that were specifically bound by IVIG molecules. Many of these Fabs reacted with platelets. Sequencing revealed that the most frequently used germ-line gene segments of all IVIG-bound Fabs were identical to those observed for many other autoantibodies. Particularly, the loci 3–30 or 3–30/3–30.5, 3–23 and 3r, 3l, and 2a2 represented the most abundant genes used for the heavy (VH) and light chain V region (VL), respectively. This suggested a specific interaction of IVIG molecules with B cells that present B cell receptors derived from these germ-line genes. In the current study we determined the genetic origin of IVIG-reactive IgG and IgM cloned from a healthy person. A favoured selection of antibodies derived from the same germ-line origins as in AITP was observed. Because 3–30 and 3–23 are the most frequently rearranged VH germ-line gene segments among human B cells, our results suggest that this favoured anti-idiotypic interaction may have an important role for the development and control of the normal B cell repertoire.
Cytokine dysregulation in activated cystic fibrosis (CF) peripheral lymphocytes
Authors: Moss R B , Hsu Y-P , Olds L 
Published: March 2003

SUMMARYRecent studies demonstrate in vivo and in vitro cytokine dysregulation in CF epithelial cells. To see if these abnormalities may be generalized to other cells expressing cystic fibrosis transmembrane conductance regulator (CFTR) but not directly exposed to local inflammation, we studied mRNA transcription, intracellular protein production and extracellular secretion of IL-2, IL-4, IL-5, IL-10 and interferon-gamma (IFN-γ) from freshly isolated blood mononuclear and CD4+ T cells from CF patients and controls. Cells were activated by phorbol myristate acetate (PMA) and anti-CD3, PMA–ionomycin, or lipopolysaccharide (LPS) and assessed for cytokine mRNA transcription by semiquantitative reverse transcriptase-polymerase chain reaction, intracellular protein production by flow cytometry, and secretion by supernatant ELISA. Cytokine expression was highly stimulus-dependent. CF cells showed higher IL-10 transcription than control cells after maximal activation by LPS (P = 0·01); despite this, cytokine production and secretion were equivalent to controls. CF cells showed lower cellular IL-10 production after PMA-anti-CD3 activation (P = 0·002). CF cells secreted less IFN-γ than control cells after maximal activation by PMA-anti-CD3 (1836 ± 273 pg/ml versus 9635 ± 3437 pg/ml, P = 0·04). IL-2, IL-4 and IL-5 regulation was similar to controls. We conclude that CF mononuclear cells show selective cytokine dysregulation after maximal activation, namely reduced IFN-γ secretion and increased IL-10 mRNA without increased production or secretion. These findings extend defects described in respiratory epithelial cells to circulating immunoregulatory cells, suggesting a link between CF genotype and cytokine dysregulation.
The endothelium is an extrahepatic site of synthesis of the seventh component of the complement system
Authors: Langeggen H , Pausa M , Johnson E , Casarsa C , Tedesco F 
Published: March 2003

SUMMARYThe level of the terminal complement components secreted by human umbilical vein endothelial cells (HUVEC) was measured by a sensitive ELISA which allows the detection of 30–50 pg/ml of these components. C7 was the only terminal component detected in measurable amounts in the cell supernatant. The mean value was 11 ng/106 cells at 96 h and was slightly higher than that of C3 (9 ng/106 cells). HUVEC and serum C7 analysed by SDS–PAGE and immunoblot exhibited the same electrophoretic mobility. A proportion of C7 secreted by HUVEC was incorporated into the terminal complement complex (TCC) assembled spontaneously in the supernatant of cells cultured in C7-deficient human serum, and was not detected by the standard ELISA for C7 measurement. By adding the amount of C7 present in the TCC to that of free C7, the total amount of the component released by HUVEC was calculated to be approximately 35 ng/106 cells. Further TCC was produced following complement activation of the cell supernatant through the alternative pathway. Synthesis of C7 by HUVEC was confirmed by inhibition experiments in the presence of cycloheximide and by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of C7 mRNA expression. Addition of IL-1α and tumour necrosis factor-alpha to the cell culture stimulated the secretion of C3, but had no effect on the synthesis of C7. By contrast, interferon-gamma had only a marginal effect on the production of C3, but markedly down-regulated the synthesis of C7 as assessed both by ELISA and RT-PCR.
Effects of secretory leucocyte protease inhibitor on the production of the anti-inflammatory cytokines, IL-10 and transforming growth factor-beta (TGF-β), by lipopolysaccharide-stimulated macrophages
Authors: Sano C , Shimizu T , Sato K , Kawauchi H , Tomioka H 
Published: March 2003

SUMMARYWe studied the effects of secretory leucocyte protease inhibitor (SLPI) on the production of the anti-inflammatory cytokines, IL-10 and TGF-β, by lipopolysaccharide (LPS)-stimulated macrophages, using half-sized SLPI (1/2 SLPI) containing the C-terminal domain (Arg58-Ala107). ELISA testing of macrophage culture fluids showed a temporary production of IL-10 by the macrophages in the early phase (24 h) after LPS stimulation at low (1 ng/ml) or high (10 μg/ml) concentrations. On the other hand, TGF-β production was initiated after day 3 and progressively increased. 1/2 SLPI significantly increased IL-10 and TGF-β production by macrophages in response to a low dose as well as a high dose of LPS. Reverse transcription-polymerase chain reaction analysis showed that 1/2 SLPI caused a significant increase in the expression of both IL-10 and TGF-β mRNAs by LPS-stimulated macrophages. Thus, although the profile of macrophage TGF-β production by LPS-stimulated macrophages is markedly different from that of their IL-10 production, SLPI causes an up-regulation of the production of these anti-inflammatory cytokines by LPS-stimulated macrophages.
Expression of MHC class II in T cells is associated with increased HIV-1 expression
Authors: Saifuddin M , Spear G T , Chang C-H , Roebuck K A 
Published: March 2003

SUMMARYHIV-1 replicates in activated T cells at significantly higher levels than in resting cells. Thus, certain molecules up-regulated during T cell activation appear to be important for HIV-1 replication. In this study, we present evidence suggesting that expression of MHC class II (class II) molecules on CD4+ T cells facilitate HIV-1 replication. T cells that expressed class II supported greater virus replication than T cells lacking class II. The class II+ cells, when either infected with HIV-1 or transfected with an env-minus HIV-1 provirus plasmid, produced 10–20-fold greater virus expression than class II− cells. Anti-class II antibody markedly inhibited virus expression in class II+ cells (but not class II− cells) and also decreased the nuclear binding activity of AP-1, an inducible transcription factor important in T cell activation and HIV-1 expression. Most importantly, the induction of class II expression by transfection of the MHC class II transactivator (CIITA) stimulated HIV-1 replication in Jurkat T cells. Taken together, these data suggest that expression of MHC class II molecules and/or CIITA in T cells enhances HIV-1 transcription.
Changed colonic profile of P-selectin, platelet-endothelial cell adhesion molecule-1 (PECAM-1), intercellular adhesion molecule-1 (ICAM-1), ICAM-2, and ICAM-3 in inflammatory bowel disease
Authors: Vainer B , Nielsen O H 
Published: March 2003

SUMMARY
Cell adhesion molecules (CAM) are essential for the capture and migration of leucocytes. Ulcerative colitis (UC) and Crohn's disease (CD) are characterized by a continuous infiltration of leucocytes into intestinal tissue, and the colonic contents of P-selectin, PECAM-1, ICAM-1, ICAM-2, and ICAM-3 were therefore studied. Concentrations of these cell adhesion molecules were measured by an ELISA technique in sonicated colonic tissue from patients with UC and CD and controls with non-inflammatory disease and compared with the diagnosis and disease activity. P-selectin, PECAM-1, and ICAM-1 concentrations were elevated in UC patients compared with controls (P = 0.034, P = 0.014, P = 0.017, respectively), whereas that of ICAM-2 was not. The concentrations of these CAM did not differ in CD. In contrast, higher concentrations of ICAM-3 were found in the CD patients than in either UC (P = 0.001) or controls (P = 0.004). The CAM concentrations increased with disease activity, although only ICAM-1 was significantly elevated (P = 0.017). As considerable differences were found between UC and CD with comparable stages of inflammation, the mere presence of inflammation cannot solely explain the results. The observed differences in the CAM concentrations in UC and CD support the hypothesis that UC and CD are two distinct disease entities with separate pathogenic mechanisms.
Angiogenesis in inflammatory joint disease: a target for therapeutic intervention
Authors: Brenchley P E C 
Published: March 2003

SUMMARYThe evidence reviewed here clearly supports the concept that pathological angiogenesis is an important component in inflammatory joint erosion. Of the primary angiogenic factors, VEGF-A is clearly a key participant in this mechanism and a range of anti-VEGF strategies is being developed to neutralize its biological function [54,55]. Currently available drugs are also being screened for VEGF antagonistic effects. In a study of the effects of existing disease-modifying anti-rheumatic drugs on cultured synovial cells, bucillamine and dexamethasone showed significant inhibition of VEGF production [56]. In addition, COX-1 and COX-2 non-steroidal anti-inflammatory drugs have been shown to inhibit angiogenesis by blocking VEGF-induced signal transduction [57]. Modulation of the immune network in RA using TNF-α antagonists is producing promising results, but as outlined in this review, this treatment on its own is unlikely to control joint angiogenesis. It is possible that combination therapy, e.g. TNF-α antagonist and a VEGF signal transduction inhibitor, will be more effective by using antagonists that block different but key control points in the disease pathology.
Distribution of age-related thymulin titres in normal subjects through the course of life
Authors: Consolini R , Legitimo A , Calleri A , Milani M 
Published: March 2003

SUMMARYThe thymus has a dominant immunological role in utero and in early childhood, being a primary source of T lymphopoiesis, and its investigation may be particularly relevant for the immunological study of paediatric patients. Thymulin, a nonapeptide secreted by the thymus, is an essential hormone for T lymphocyte differentiation and function. As thymulin values in the normal population have not been well documented, especially for children under the age of 1 year, we detail thymic endocrine function by presenting age-related plasma thymulin levels in a large series (n = 93) of healthy individuals, ranging from birth to old age. We demonstrate that thymulin is already detectable at birth; it then gradually increases with age, reaching the highest level in children aged 5–10 years. Starting at adolescence, thymulin titres gradually start to fall, reaching the lowest value at 36 years of age and remaining steady until 80 years (the oldest person tested).
The effect of testosterone replacement treatment on immunological features of patients with Klinefelter's syndrome
Authors: Koçar I H , Yesilova Z , Özata M , Turan M , Sengül A , Özdemir I Ç 
Published: March 2003

SUMMARYAlthough the effects of androgen deficiency in the immune system have long been appreciated, little is known about the immunological features of patients with Klinefelter's syndrome (KS). On the other hand, interest in androgens as a possible treatment for some autoimmune diseases is growing. In the present study, some immunological parameters were evaluated in 26 patients with KS prior to androgen replacement treatment (ART) and the results were compared with those in 19 healthy control subjects. Patients were then treated with testosterone for 6 months and the pre- and post-treatment findings were compared. Serum levels of IgG, IgA, IgM, C3c and C4 were measured by nephelometry and lymphocyte subsets and CD4+/CD8+ ratios were examined by flow cytometry. IL-2 and IL-4 levels were measured by ELISA. Pretreatment levels of the serum IgA, IgG, IgM, IL-2 and IL-4 of the patients were higher than those of the controls and were all decreased significantly following ART. The pretreatment absolute numbers and percentages of CD3+, CD4+, CD19+ cells and CD4+/CD8+ ratios of patients with KS were higher than those of the controls and were all decreased with ART. Percentages of CD8+ cells were increased significantly, while C3 and C4 levels were both significantly decreased after ART. It is concluded that the lack of testosterone in patients with KS enhances cellular and humoral immunity and that ART may suppress this.
TNFA promoter polymorphism and susceptibility to brucellosis
Authors: Caballero A , Bravo M J , Nieto A , Colmenero J D , Alonso A , Martín J 
Published: March 2003

SUMMARYThe aim of this study was to investigate the possible influence of the tumor necrosis factor alpha (TNFA) gene promoter polymorphisms and HLA class II genes on the susceptibility to or development of human brucellosis. TNFA genotypes (at positions −308 and −238) were determined in 59 patients with brucellosis and 160 healthy controls by polymerase chain reaction-restriction fragment length polymorphism. There were no significant differences between the patients and the controls for the TNFA-238 genotypes. However, when the overall TNFA-308 genotype distribution of the brucella patients was compared with that of the control subjects, a significant skewing was observed (P = 0·02). The TNFA-308.1/2 genotype was present at significantly higher frequency in the total patient as a whole compared with control subjects (30% versus 15%; P = 0·01, odds ratio (OR) 2·49, 95% confidence interval (CI) 1·16–5·33). No statistically significant differences in the distribution of HLA-DRB1 or DQB1 alleles were observed between brucella patients and control subjects. Stratification to correct for interdependence of TNFA-308.2 and HLA-DR3 alleles confirmed that, in spite of their strong linkage disequilibrium, the association of TNFA-308.2 with brucellosis was independent of HLA-DR3.
Macrophage inflammatory protein-1α(MIP-1α), MIP-1β, and RANTES mRNA semiquantification and protein expression in active demyelinating multiple sclerosis (MS) lesions
Authors: Boven L A , Montagne L , Nottet H S L M , De Groot C J A 
Published: March 2003

SUMMARYMS is a demyelinating disease characterized by infiltration of monocytes and lymphocytes into the brain parenchyma, destruction of oligodendrocytes and loss of myelin. Since chemokines play a major role in the migration of monocytes and T cells, we here investigated the expression of the CC chemokines MIP-1α, MIP-1β, and RANTES in brain tissue from MS patients using reverse transcriptase-polymerase chain reaction techniques. Both MIP-1β as well as RANTES were found to be significantly elevated in brain tissue of MS patients. In addition, MIP-1α was also increased, although not significantly. Immunohistochemistry revealed that, whereas RANTES was mainly localized in reactive astrocytes, MIP-1α and MIP-1β immunoreactivity was predominantly found in perivascular and parenchymal macrophages, containing myelin degradation products. Thus, chemokines appear to be associated with MS and an increased chemokine expression may further enhance disease progression by attracting more leucocytes into the brain parenchyma and by activation of effector functions of astrocytes and microglial cells.