bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-stimulatory signals increase the reactivity ofγδT cells towards mycobacterial antigens
Authors: González-Amaro R , Portales-Pérez D P , Baranda L , Moncada B , Toro C , López-Briones S , Espitia C , Mancilla R 
Published: March 2003

SUMMARYAlthough it has been shown that γδ T lymphocytes are able to react with different cell-associated or soluble antigens, the immune repertoire of these cells appears to be skewed to the recognition of mycobacterial antigens. We have studied the number and reactivity of γδ T cells towards several mycobacterial antigens in patients with tuberculosis and leprosy, as well as their healthy contacts and control individuals. We found an increased number of Vδ2+ cells in healthy contacts (PPD+ and lepromin+) and tuberculoid leprosy patients. The γδ T cells from lepromatous leprosy showed a decreased response to all antigens tested, but some of these patients exhibited a significant response to the 30-kD glycoprotein of Mycobacterium tuberculosis. Interestingly, the reactivity of γδ T cells against mycobacterial antigens was significantly increased by costimulatory signals generated through CD7, LFA-1, CD50 and CD69 in all groups. However, signalling through CD69 did not enhance the responsiveness of γδ lymphocytes from lepromatous patients. On the other hand, the in vitro blockade of IL-10 with a specific antibody enhanced the cell proliferation of γδ lymphocytes from lepromatous leprosy patients, whereas exogenous IL-10 had an opposite effect in most individuals studied. These results suggest the potential role of different cell membrane receptors in the regulation of γδ T cell proliferation induced by mycobacteria, as well as the possible involvement of IL-10 in this phenomenon.
Inhibition of cyclin A gene expression in human B cells by an immunosuppressant mizoribine
Authors: Hirohata S , Nakanishi K , Yanagida T 
Published: March 2003

SUMMARYMizoribine has been shown to have beneficial effects in the treatment of rheumatoid arthritis and lupus nephritis, in which abnormal B cell functions are involved. Previous studies demonstrated that mizoribine directly suppresses the function of human B cells. The current study explored in detail the mechanism of the suppression of human B cell responses by mizoribine at the molecular level. Highly purified peripheral blood B cells obtained from normal healthy individuals were stimulated with Staphylococcus aureus Cowan I (SAC) plus IL-2 in the presence or absence of mizoribine or methotrexate for 48 h to 72 h. The expression of cyclin A mRNA was determined by semiquantitative reverse transcriptase-polymerase chain reaction followed by Southern hybridization. Although at pharmacologically attainable concentrations both mizoribine and methotrexate suppressed the production of IgM of SAC-activated B cells, mizoribine, but not methotrexate, decreased the expression of cyclin A protein as well as mRNA in B cells stimulated with SAC + IL-2. Of note, mizoribine facilitated the degradation of cyclin A mRNA in the presence of actinomycin D, indicating that mizoribine shortens the stability of cyclin A mRNA. The results indicate that mizoribine suppresses the expression of cyclin A mRNA in human B cells by down-regulating its stability, and thus down-regulates their responses.
Cyclosporin A reduces expression of adhesion molecules in the kidney of rats with chronic serum sickness
Authors: Rincón J , Parra G , Quiroz Y , Benatuil L , Rodríguez-Iturbe B 
Published: March 2003

SUMMARY
Treatment with cyclosporin A (CsA) improves proteinuria and reduces renal cellular infiltration in chronic serum sickness (CSS). We examined if these effects were associated with a reduced renal expression of CD54 and its ligands, interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and MHC class II molecules. We studied two groups of rats in which CSS was induced by daily injections of ovalbumin (OVA): a group treated with CsA (OVA.CsA group, n = 11) and a group that received no treatment (OVA.CSS group, n = 11). An additional group of five rats (control group) received only phosphate buffer. Immunostaining techniques were used to follow CSS and to study the expression of CD54, CD18, CD11b/c, IFN-γ, TNF-α and MHC class molecules. Proteinuria (mg/24 h) was reduced from 248.2 ± 73.1 (OVA.CCS group) to 14.5 ± 13.1 with CsA treatment (P &lt; 0.0001). The renal expression of CD54 and its ligands (CD18 and CD11b/c) was reduced by 50% to 75%. Correspondingly, there was a 60% to 85% reduction in the number of infiltrating leucocytes. The number of cells expressing TNF-α, IFN-γ and MHC II molecules was also reduced. CsA reduces expression of CD54 and its ligands. This effect is associated with a reduction of cellular infiltration, IFN-γ, TNF-α-producing cells and with MHC II expression in the kidney. These findings suggest that expression of adhesion molecules plays a critical role in CSS and underline the importance of cellular immunity in this experimental model.
Staphylococcal toxin-induced T cell proliferation in atopic eczema correlates with increased use of superantigen-reactive Vβ-chains in cutaneous lymphocyte-associated antigen (CLA)-positive lymphocytes
Authors: Davison S , Allen M , Vaughan R , Barker J 
Published: March 2003

SUMMARYStaphylococcal superantigens have been implicated in the pathogenesis of atopic dermatitis (AD). This may occur through superantigenic activation of T lymphocytes and their subsequent induction of the skin homing receptor CLA on activated cells. We investigated the proliferative responses of peripheral blood mononuclear cells (PBMC) from 10 patients with an infective exacerbation of AD and six normal controls to the staphylococcal superantigens, staphylococcal enterotoxin A and B (SEA, SEB) and toxic shock syndrome toxin-1 (TSST-1), and the mitogens phytohaemagglutinin (PHA) and concanavalin A (Con A). We also assessed CLA and T cell receptor (TCR) Vβ-chain expression by immunofluorescence and flow cytometry before and after stimulation. PBMC from AD patients showed two-fold increased proliferation to SEA and SEB (P &lt; 0·01) compared with normals, whereas the response to mitogenic stimulation was identical. Analysis of (TCR) Vβ-chain expression demonstrated increased use of superantigen-reactive Vβ families in freshly isolated PBMC in AD patients compared with controls. This pattern of Vβ-chain expression was only observed in the CLA+ but not the total population of T cells. Furthermore, there was a positive correlation between the enhanced PBMC proliferative response and increased expression of superantigen-reactive Vβ families in atopic patients. These data support the concept that superantigens are important in the pathogenesis of this common condition, and also provide evidence that the increased use of certain Vβ families in circulating, CLA+, skin homing lymphocytes is of functional significance.
Expression of vascular endothelial growth factor by synovial fluid neutrophils in rheumatoid arthritis (RA)
Authors: Kasama T , Kobayashi K , Yajima N , Shiozawa F , Yoda Y , Takeuchi H T , Mori Y , Negishi M , Ide H , Adachi M 
Published: March 2003

SUMMARYMost of the leucocytes infiltrating rheumatoid synovial fluid (SF) are neutrophils capable of producing a variety of inflammatory mediators known to contribute significantly to the disease process during active RA. In the present study, we investigated the contribution made by SF neutrophils to the elevated levels of vascular endothelial growth factor (VEGF) seen in rheumatoid SF. Rheumatoid SF neutrophils were found to contain significantly larger amounts of both VEGF protein and its mRNA than peripheral blood neutrophils from either RA patients or healthy controls. Levels of celL-associated VEGF were well correlated with free VEGF in SF, which was significantly higher than in SF from osteoarthritis patients. Levels of SF neutrophiL-associated VEGF also correlated with RA disease activity and cell surface integrin expression. Thus, SF neutrophiL-associated VEGF may be considered an indicator of both local and systemic inflammation of RA, contributing to the neovascularization seen during RA synovitis.
Booster immunization of children with an acellular pertussis vaccine enhances Th2 cytokine production and serum IgE responses against pertussis toxin but not against common allergens
Authors: Ryan E J , Nilsson L , Kjellman N-I M , Gothefors L , Mills K H G 
Published: March 2003

SUMMARY
Acellular pertussis vaccines (Pa) protect against severe pertussis in children. However, serum antibody responses decline quickly after immunization. Studies in animal models suggest that cell-mediated immunity also contributes to protection against Bordetella pertussis, and it has already been demonstrated that Pa induce T cells that secrete type-1 and type-2 cytokines in children. In this study we examined the persistence of the T cell response and the effect of booster immunization in 4–6-year-old children. Cell-mediated immunity to B. pertussis antigens was detected in a high proportion of children more than 42 months after their last immunization. Peripheral blood mononuclear cells (PBMC) from the majority of children secreted interferon-gamma (IFN-γ) and a smaller proportion IL-5, in response to specific antigen stimulation in vitro. However, following booster immunization, significantly higher concentrations of IL-5, but not IFN-γ, were produced by PBMC in response to B. pertussis antigens. Furthermore, plasma IL-4 and IL-5 concentrations were increased, whereas IFN-γ concentrations were reduced following booster immunization. It has been suggested that childhood immunization with Th2-inducing vaccines may predispose some children to atopic disease. Although we found that pertussis toxin (PT)-specific IgE was significantly increased after booster immunization in both atopic and non-atopic children, the levels of IgE to common allergens and the prevalence of positive skin prick test were unaffected by the booster vaccination. Thus, despite the enhancement of type-2 responses to B. pertussis antigens, booster vaccination with Pa does not appear to be a risk factor for allergy.
B cell epitopes of gliadin
Authors: Osman A A , Günnel T , Dietl A , Uhlig H H , Amin M , Fleckenstein B , Richter T , Mothes T 
Published: March 2003

SUMMARYA phage displayed dodecapeptide library and synthetic octapeptides spanning the complete sequence of α- and γ-type gliadin and overlapping in six amino acids (pepscan) were screened for binding to human gliadin antibodies (AGA). Phage display experiments led to four sequences recognized with significantly higher frequency by sera with raised IgA-AGA titres than by control sera. All these peptides contained the core sequence PEQ. Pepscan experiments revealed binding of AGA to five prominent regions: (i) QXQPFP (binding to IgG and IgA, X representing P, Q, and L); (ii) IPEQ (IgG) and WQIPEQ (IgA); (iii) FFQP (IgG) and QGXFQP (IgA, X representing F and S); (iv) PQQLPQ (IgG and IgA), all in α-type gliadin; and (v) QPQQPF (IgG and IgA) in γ-type gliadin. In two of the sequences (QPQQPF and QQQPFP), substitution of Q by E resulting in QPEQPF and QEQPFP, respectively, increased significantly binding of AGA from sera of patients with biopsy-proven or suspected coeliac disease (CoD), all positive for endomysium antibodies (EmA). In contrast, binding of sera with high AGA titre from EmA-negative patients (CoD and dermatitis herpetiformis excluded) was not enhanced by this substitution. Thus, AGA directed against these modified epitopes can be regarded as specific for CoD. This is the first study demonstrating that deamidation of gliadin improves reactivity of AGA of CoD patients.
Significance of chemokines and activated platelets in patients with diabetes
Authors: Nomura S , Shouzu A , Omoto S , Nishikawa M , Fukuhara S 
Published: March 2003

SUMMARYLevels of platelet-derived microparticles (PMPs), platelet activation markers (P-selectin expressed on, or annexin V binding to, platelets (plt:P-selectin or plt:annexin V, respectively)), chemokines (IL-8, monocyte chemotactic peptide-1 (MCP-1), and regulated on activation normally T-cell expressed and secreted (RANTES)), and soluble P- and E-selectins were compared in peripheral blood from diabetic and control patients in order to develop a better understanding of their potential contribution to diabetic vascular complications. Significant increases were found for PMPs, plt:P-selectin, MCP-1, RANTES and soluble P- and E-selectins in diabetic individuals, whereas IL-8 levels were similar. Furthermore, after ticlopidine treatment, most of these factors receded to baseline levels observed in non-diabetic patients. Our findings indicate that ticlopidine might be able to prevent or reduce vascular complications in diabetic patients.
Antigen-specific T cell responses in human peripheral blood leucocyte (hu-PBL)–mouse chimera conditioned with radiation and an antibody directed against the mouse IL-2 receptorβ-chain
Authors: Cao T , Leroux-Roels G 
Published: March 2003

SUMMARYA weakness of the hu-PBL–SCID model for the study of human immune functions is the appearance of anergy and the consequent loss of T cell function. We demonstrate here that human T cells retain normal functions during the early stage of chimerism. At 1 and 2 weeks post-engraftment, T cells isolated from the peritoneal cavity of hu-PBL chimeras could be activated and proliferated upon stimulation with phytohaemagglutinin (PHA) or specific antigens to which the cell donor was known to be immune. T cells derived from hu-PBL–SCID and hu-PBL–NOD/LtSz-scid (NOD/SCID) mice not only proliferated but also produced interferon-gamma (IFN-γ) and IL-5 following in vitro stimulation with tetanus toxoid (TT) or hepatitis B surface antigen (HBsAg). These antigen-specific T cells could only be demonstrated when cognate antigen was administered together with or immediately following the PBL transfer. Without an early rechallenge with antigen in vivo, no TT- or HBsAg-specific T cell responses could be elicited, showing the vulnerability and antigen-dependence of the T cell response. Vigorous anti-TT or anti-HBs responses could be observed in all chimeras. Administration of antigen together with the PBL graft enhanced the humoral anti-TT response in SCID and NOD/SCID mice but had little effect on the anti-HBs antibody response in NOD/SCID mice. These data confirm the observation that the B cell compartment in hu-PBL–SCID chimera is largely antigen-independent and extend this to SCID/NOD.
The protective effects of omega-6 fatty acids in experimental autoimmune encephalomyelitis (EAE) in relation to transforming growth factor-beta 1 (TGF-β1) up-regulation and increased prostaglandin E2 (PGE2) production
Authors: Harbige L S , Layward L , Morris-Downes M M , Dumonde D C , Amor S 
Published: March 2003

SUMMARYPolyunsaturated fatty acids are known to affect the immune response and administration of the omega-6 fatty acid linoleic acid has been reported to be beneficial in multiple sclerosis (MS) and EAE. In this study we have investigated the effects of oral feeding of plant lipid rich in the omega-6 fatty acid gamma-linolenic acid from Borago officinalis on acute and relapse disease and the immune response in EAE using SJL mice. EAE was induced by an encephalitogenic peptide (92–106) of myelin oligodendrocyte glycoprotein (MOG), and mice were fed the plant lipid daily from 7 days after EAE induction to assess the effects on acute disease and from day 25 to assess the effects on disease relapse. The clinical incidence and histological manifestations of acute EAE, and the clinical relapse phase of chronic relapsing EAE (CREAE) were markedly inhibited by omega-6 fatty acid feeding. A significant increase in the production of TGF-β1 in response to concanavalin A (Con A) at day 13 and a significant increase in TGF-β1 and PGE2 to Con A, PPD and MOG peptide (92–106) at day 21 were detected in spleen mononuclear cells from fatty acid-fed mice. There was no difference in interferon-gamma, IL-4 and IL-2 production between the fatty acid-fed and control groups. Significantly higher TGF-β mRNA expression was found in the spleens of omega-6 fatty acid-fed mice at day 21. There were no differences in spleen cell proliferative response to Con A, PPD and MOG peptide (92–106). Biochemical analysis of spleen cell membrane fatty acids revealed significant increases in the eicosanoid precursor fatty acids dihomo-γ-linolenic acid and arachidonic acid in response to gamma-linolenic acid feeding, indicating rapid metabolism to longer chain omega-6 fatty acids. These results show that oral feeding of gamma-linolenic acid-rich plant lipid markedly affects the disease course of acute EAE and CREAE and is associated with an increase in cell membrane long chain omega-6 fatty acids, production of PGE2 and gene transcription and, on activation, secretion of TGF-β1.
Tears contain the complement regulator CD59 as well as decay-accelerating factor (DAF)
Authors: Cocuzzi E , Szczotka L B , Brodbeck W G , Bardenstein D S , Wei T , Medof M E 
Published: March 2003

SUMMARYPrevious studies have shown that DAF (or CD55), a cell surface inhibitor of autologous C3 activation, is present in tears and that &gt; 90% of the C3 convertase regulatory activity in tear fluid resides in this protein (Lass JH et al., Invest Ophth Vis Sci 1990; 31:1136–48). This study investigated whether (i) the membrane cofactor protein (MCP or CD46), an additional factor that regulates C3 activation, and (ii) the membrane inhibitor of reactive lysis (MIRL or CD59), a cell surface regulator that acts to prevent formation of the membrane attack complex, are also present in tears, and if so, are functional. Two-site immunoradiometric assays showed that MCP is present in tears at low levels (42 + 8 ng/ml, n = 8) while CD59 is present at levels (222 + 78 ng/ml, n = 14) comparable to those of DAF (325 + 289 ng/ml, n = 12). The concentrations of CD59 (i) were increased two-fold or more in closed eye tears, and (ii) were decreased in reflex tears. Western blotting showed that CD59 protein in tears migrates with an apparent mol. wt similar to membrane CD59 protein. Phenyl–Sepharose adsorption and Triton X-114 partitioning of tear CD59 as well as of tear DAF however, showed that both proteins are devoid of GPI anchors. Assays using cobra venom factor-activated human serum and guinea pig erythrocytes showed that CD59 is functionally active in inhibiting autologous C5b-9-mediated lysis and, under constitutive conditions, accounts for &gt; 85% of the C9 inhibitory activity in tear fluid.
Apoptosis signals in atopy and asthma measured with cDNA arrays
Authors: Brutsche M H , Brutsche I C , Wood P , Brass A , Morrison N , Rattay M , Mogulkoc N , Simler N , Craven M , Custovic A , Egan J J G , Woodcock A 
Published: March 2003

SUMMARYA variety of studies have stressed the importance of the control of inflammatory cell longevity and the balance of pro-survival and pro-apoptotic signalling. Recently, asthma was found to be associated with reduced apoptosis of inflammatory cells in lung tissue. The aim of the study was to investigate the systemic activation of apoptosis pathways using cDNA array technology in atopy and asthma. Eighteen atopic asthmatics (AA), eight atopic non-asthmatic (AN) and 14 healthy control subjects (C) were included in the study. Peripheral blood mononuclear cells were separated with gradient centrifugation, mRNA purified and the reverse-transcribed probes hybridized to cDNA arrays. The signals were compared by standardizing to the 100 most expressed genes and group differences assessed with the Mann–Whitney U-test. We found a concerted up-regulation of several pro-survival cytokines and growth factors in AN and AA. FAS and FASL were not differentially expressed, but FAST kinase was over-expressed in AN and AA. The tumour necrosis factor pathway was activated in AN and AA with increased cytokine and receptor levels and increased TRAF2, an intracellular signalling product. There were indications of a down-regulated p53 system. In contrast, the Bcl-2 family of genes showed a net pro-apoptotic profile in AN and AA. The group of caspases showed a constant gene expression pattern in all groups. In conclusion, significant differences in the expression of apoptosis-related genes were found in peripheral blood of atopic individuals with and without asthma. cDNA array technology proved to be useful and may be complementary to DNA-based studies in order to analyse interactive and multidimensional pathways as shown here for apoptosis.
Anti-inflammatory cytokine IL-10 and T cell cytokine profile in periodontitis granulation tissue
Authors: Lappin D F , Macleod C P , Kerr A , Mitchell T , Kinane D F 
Published: March 2003

SUMMARYTh2 cells are more abundant than Th1 cells in periodontitis lesions, but the relative importance of the Th1 and Th2 subsets in periodontal disease is not understood. In addition, the role of proinflammatory and anti-inflammatory cytokines in this disease process is unclear. Biopsies were obtained from 10 patients with early onset periodontitis (EOP) and 10 patients with adult periodontitis (AP). From all of the patients in the AP group we were able to obtain and section the gingival tissue to serve as controls. We used polyclonal monospecific antibodies to detect cells expressing IL-2, IL-4, IL-6, IL-10 and IL-15, tumour necrosis factor (TNF-α) and interferon-gamma (IFN-γ) in formalin-fixed, paraffin-embedded sections of granulation tissue from periodontitis lesions. We also employed a series of oligonucleotide probes to detect cells expressing the cytokine transcripts in the same tissue biopsies. Cells that expressed IL-4 or IL-6 were more numerous than cells expressing either IL-2 or IFN-γ. Th2 cells were more numerous in EOP and AP tissues. IL-15 substitutes for IL-2 in a number of biological activities related to the Th1 immune response, and interestingly, in periodontal lesions the IL-15-expressing cells outnumbered IL-2-expressing cells, suggesting that this is the pattern of immune regulation by T cells in the periodontium. The functional balance in the T cell subsets detected by their cytokine profiles underlies the importance of the anti-inflammatory mechanisms taking place in the diseased tissue. The numbers of inflammatory leucocytes that express the anti-inflammatory cytokine IL-10 are much more widely distributed than those that express the proinflammatory cytokines IL-6 and TNF-α. This study suggests that large numbers of infiltrating inflammatory cells as well as accessory cells are involved in the down-regulation of the inflammatory and immune response in periodontitis.
The impact of CMV on the respiratory burst of macrophages in response toPneumocystis carinii
Authors: Laursen A L , Mogensen S C , Andersen H M K , Andersen P L , Ellermann-Eriksen S 
Published: March 2003

SUMMARYInfection of human monocyte-derived macrophages with CMV decreased the respiratory burst when cells were stimulated with opsonized zymosan or Pneumocystis carinii (P. carinii). Such an effect, though smaller, was also seen with heat-inactivated CMV, but only when triggered by zymosan. The effect was most pronounced in cells obtained from CMV antibody-negative donors. Dexamethasone further reduced the respiratory burst, both in uninfected and CMV-infected cells. Interferon-γ increased the response in uninfected cells and, to a lesser extend, in cells treated with heat-inactivated CMV, whereas no effect was seen with infective CMV. No overt productive infection or cytopathology could be detected, however, the monocytes incubated with infective but also heat-inactivated CMV formed clusters, a phenomenon that was equally pronounced in cultures from CMV antibody positive and negative-donors. These results might help explain the worse prognosis of P. carinii pneumonia in patients coinfected with CMV and receiving dexamethasone.