bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decreased T-bet expression and changes in chemokine levels in adults with asthma
Authors: Ko F W S , Lun S W M , Wong C K , Szeto C C , Lam C W K , Leung T F , Hui D S C 
Published: October 2008

SummaryT-bet is a novel transcription factor regulating lineage commitment of T helper (Th) lymphocytes to a predominant Th1 phenotype. Previous studies on T-bet and asthma focused mainly on bronchial biopsy specimens. This study assessed the relationship between T-bet expression and levels of selected chemokines in the peripheral blood of asthmatics. Blood was collected from 24 steroid-naive asthmatics, 39 asthmatics on inhaled corticosteroid and 32 age- and sex-matched controls for assay of T-bet expression, specific IgE and chemokines (interferon-gamma inducible protein-10 (IP-10/CXCL10), monokines induced by interferon-gamma (MIG/CXCL9), monocyte chemotactic protein-1 (MCP-1/CCL2), regulated upon activation normal T cell expressed and secreted (RANTES/CCL5) and interleukin-8 (IL-8/CXCL8) levels. T-bet mRNA expression was assessed by real-time quantitative reverse transcription–polymerase chain reaction (RT–PCR). Chemokine levels were assessed by immunofluorescence flow cytometry. The mean (s.d.) age and forced expiratory volume in 1 s (FEV1)% predicted of the asthmatics were 43·6 (14·6) years and 85·9 (20·0)%, respectively. The median (IQR) T-bet expression after normalization with β-actin was suppressed in asthmatics versus controls [asthmatics 0·71 (0·59) versus controls 1·07 (1·14), P = 0·03]. The median (IQR) of plasma RANTES was elevated, whereas IP-10 was suppressed in asthmatics versus controls (RANTES: 13 658·0 (13673·3) versus 6299·5 (19 407·8) pg/ml, P = 0·03; IP-10: 1047·6 (589·8) versus 1306·4 (759·9) pg/ml, P = 0·001). There was a weak and negative correlation between T-bet expression and RANTES level in the asthmatics (r = –0·29, P = 0·032). T-bet could be measured in peripheral blood and its expression was suppressed in asthmatics. This is in keeping with asthma being a predominantly Th2 disease and T-bet probably plays a role in the pathogenesis of asthma. Further studies are needed to explore the potential application of peripheral blood monitoring of T-bet.
Infection of mice with respiratory syncytial virus during neonatal life primes for enhanced antibody and T cell responses on secondary challenge
Authors: Tasker L , Lindsay R W B , Clarke B T , Cochrane D W R , Hou S 
Published: October 2008

SummaryPrimary neonatal immune responses to infection or vaccines are weak when compared with those of adults. In addition, memory responses of neonatally primed animals may be absent, weak or T helper type 2 (Th2)-biased. Respiratory syncytial virus (RSV) is an important pathogen of human infants and infection during the neonatal period has been linked to the development of asthma in later life. Here we report that acute intranasal infection of neonatal mice with RSV induces significant RSV-specific antibody and CD8 T cell responses. These responses were boosted after RSV rechallenge during adulthood, demonstrating the establishment of memory after neonatal priming. Primary infection during neonatal life was associated, following rechallenge, with limited viral replication in the lung. Recall responses of both spleen and lymph node cells from neonatally primed and adult-primed mice were associated with interferon-γ secretion, indicative of a Th1-type response. However, interleukin (IL)-4 and IL-5 secretion were enhanced only in spleen and lymph node cells from neonatally primed mice. Rechallenge of neonatally primed mice was also associated with increased concentrations of chemokines monocyte chemoattractant protein-1, macrophage inflammatory protein-1α and regulated upon activation normal T cell expressed and secreted in the lung. These may play a role in the enhanced inflammatory cell recruitment and immunopathology induced following RSV reinfection. Our results demonstrate therefore that immunity to RSV can be established during neonatal life and, importantly, that the quality of the subsequent response is dependent upon the age of first infection.
Regulatory T cell-associated activity in photopheresis-induced immune tolerance in recent onset type 1 diabetes children
Authors: Jonson C-O , Pihl M , Nyholm C , Cilio C M , Ludvigsson J , Faresjö M 
Published: October 2008

SummaryExtracorporeal photochemotherapy (ECP) has demonstrated immunological effects. The proposed cytotoxic lymphocyte antigen 4 (CTLA-4) involvement, together with forkhead box P3 (FoxP3) and transforming growth factor (TGF)-β are associated with regulatory T cell activity. The aim of the study was to evaluate the regulatory T cell-associated effect of ECP in recent onset type 1 diabetic (T1D) children. Children (n = 20) with T1D received photopheresis 8-methoxypsoralen + ECP or placebo + shampheresis. Peripheral blood mononuclear cells (PBMC) collected pretreatment (day 1) and post-treatment (day 90) were stimulated with phytohaemagglutinin (PHA) and T1D-associated glutamic acid decarboxylase 65 (GAD65) peptide a.a. 247–279. CTLA-4, sCTLA-4, FoxP3 and TGF-β mRNA transcription was quantified. Photopheresis-treated individuals' relative mRNA expression was generally maintained during the course of the study. Placebo individuals increased in spontaneous CTLA-4 mRNA (P &lt; 0·05) but decreased in expression after stimulation with GAD65-peptide (P &lt; 0·05) and PHA (P &lt; 0·05). Spontaneous TGF-β (P &lt; 0·05) increased whereas PHA- (P &lt; 0·01) and GAD65-peptide (P &lt; 0·01)-induced TGF-β expression decreased in the placebo group, whereas it was maintained in the treated group. Without intervention, expression of CTLA-4 and TGF-β, stimulated with PHA and GAD65 peptide, decreased with time, with a parallel reduction of GAD65-peptide and PHA-stimulated TGF-β expression. These parameters were counteracted by ECP. In conclusion, our results indicate that ECP maintains regulatory T cell-associated activity in recent-onset T1D.
Salivary human immunodeficiency virus (HIV)-1-specific immunoglobulin A in HIV-1-exposed infants in Kenya
Authors: Farquhar C , VanCott T , Bosire R , Bermudez C , Mbori-Ngacha D , Lohman-Payne B , Nduati R , Otieno P , John-Stewart G 
Published: October 2008

Summary
Humoral immunity, and specifically immunoglobulin A (IgA) that is directed against human immunodeficiency virus (HIV)-1, may contribute to protection against HIV-1 acquisition at mucosal surfaces. HIV-1-specific IgA has been detected in genital tract secretions of HIV-1-uninfected commercial sex workers with HIV-1 exposure, and may be produced in parotid saliva by infants exposed orally to HIV-1 during delivery and breastfeeding. To explore this hypothesis, we collected saliva from 145 infants aged ≤ 6 months enrolled in a perinatal HIV-1 transmission study in Nairobi and from 55 control infants without HIV-1 exposure who were born to HIV-1-seronegative mothers. Among the 145 infants, 115 (79%) remained uninfected during the 12-month study period and 30 (21%) became HIV-1-infected during follow-up. Nine (8%) of the 115 HIV-1-exposed, uninfected infants had detectable levels of HIV-1 gp160-specific IgA compared with four (13%) of 30 infected infants and none of 55 control infants (P = 0·47 and P = 0·03 respectively). Among the nine HIV-1-exposed, uninfected infants with positive assays, median age was 1 month and none acquired HIV-1 during follow-up. We conclude that HIV-1-specific salivary IgA responses may be generated by very young infants exposed perinatally to maternal HIV-1. Mucosal responses would be an appropriate target for paediatric vaccines against breast milk HIV-1 transmission.
CD26 expression on CD4+ T cells in patients with cutaneous leishmaniasis
Authors: Jafari-Shakib R , Ajdary S , Amiri Z Mohtasham , Mohammadi A M , Nourijelyani K , Mortazavi H , Shokrgozar M A , Nikbin B , Khamesipour A 
Published: October 2008

SummarySurrogate marker(s) of protection in human leishmaniasis is not well defined. In this study, T helper 1 (Th1) and Th2 cytokine profiles and CD26 expression on CD4+ T cells in peripheral blood mononuclear cells of patients with healing or non-healing forms of cutaneous leishmaniasis (CL) stimulated with Leishmania antigens were assessed. The level of interferon (IFN)-γ production was significantly higher in patients with healing or non-healing forms of CL than in healthy controls, but it was not significantly different between the two patient groups. The level of interleukin-5 production was significantly higher in patients with the non-healing form of CL than in the two other groups. There was a significant increase in the level of CD26 expression on CD4+ T cells in patients with healing (P &lt; 0·001) or non-healing (P = 0·025) forms of CL compared with the control group, but no significant difference was seen between the two patient groups. A weak positive correlation was seen between IFN-γ production and CD26 expression on CD4+ T cells of patients with the healing form of lesion (r = 0·54, P = 0·008), but this correlation was not observed in patients with the non-healing form of CL (r = 0·53, P = 0·078). Surface CD26 is not correlated with the clinical manifestation of CL or IFN-γ production. Therefore, CD26 is not a surrogate marker for IFN-γ production in CL.
Effect of tumour necrosis factor-α receptor 1 genetic deletion on carrageenan-induced acute inflammation: a comparison with etanercept
Authors: Mazzon E , Esposito E , Di Paola R , Muià C , Crisafulli C , Genovese T , Caminiti R , Meli R , Bramanti P , Cuzzocrea S 
Published: October 2008

SummaryIn the present study, we used tumour necrosis factor-α receptor 1 knock-out mice (TNF-αR1KO) to evaluate an in vivo role of TNF-αR1 on the pathogenesis of inflammatory diseases. We used a murine model of carrageenan-induced acute inflammation (pleurisy), a preclinical model of airway inflammation. The data proved that TNF-αR1KO were resistant to carrageenan-induced acute inflammation compared with TNF-α wild-type mice. TNF-αR1KO showed a significant reduction in accumulation of pleural exudate and in the number of inflammatory cells, in lung infiltration of polymorphonuclear leucocytes and lipid peroxidation and showed a decreased production of nitrite/nitrate in pleural exudates. Furthermore, the intensity and degree of the adhesion molecule intercellular adhesion molecule-1 and P-selectin, Fas ligand (FasL), inducible nitric oxide sythase and nitrotyrosine determined by immunohistochemical analysis were reduced markedly in lung tissues from TNF-αR1KO at 4 h and 24 h after carrageenan injection. Moreover, TNF-α and interleukin-1β concentrations were reduced in inflamed areas and in pleural exudates from TNF-αR1KO. To support the results generated using pleural inflammation, carrageenan-induced paw oedema models were also performed. In order to elucidate whether the observed anti-inflammatory effects were related to the inhibition of TNF-α, we also investigated the effect of etanercept, a TNF-α soluble receptor construct, on carrageenan-induced pleurisy. The treatment with etanercept (5 mg/kg subcutaneously 2 h before the carrageenan injection) reduces markedly both laboratory and histological signs of carrageenan-induced pleurisy. Our results showed that administration of etanercept resulted in the same outcome as that of deletion of the TNF-αR1 receptor, adding a new insight to TNF-α as an excellent target by therapeutic applications.
Autoantibodies against complement C1q correlate with the thyroid function in patients with autoimmune thyroid disease
Authors: Potlukova E , Jiskra J , Limanova Z , Kralikova P , Smutek D , Mareckova H , Antosova M , Trendelenburg M 
Published: October 2008

Summary
Autoantibodies against complement C1q (anti-C1q) have been well described in patients with systemic lupus erythematosus, where they correlate with the occurrence of severe lupus nephritis. However, data on anti-C1q in organ-specific autoimmune diseases are scarce. In order to determine the prevalence of anti-C1q in patients with autoimmune thyroid disorders (AITD) and a possible association with thyroid function, we measured prospectively anti-C1q in 23 patients with Graves' disease (GD) and 52 patients with Hashimoto's thyroiditis (HT). Anti-C1q levels were correlated with parameters of thyroid function and autoantibodies against thyroperoxidase, thyroglobulin and thyroid stimulating hormone (TSH) receptor. Twenty-one patients with multi-nodular goitre and 72 normal blood donors served as controls. We found elevated concentrations of anti-C1q more frequently in patients with AITD than in controls: seven of 23 (30%) patients with GD and 11 of 52 (21%) patients with HT, compared with one of 21 (5%) patients with multi-nodular goitre and six of 72 (8%) normal controls. Anti-C1q levels did not correlate with thyroid autoantibodies. However, in GD absolute levels of anti-C1q correlated negatively with TSH and positively with free thyroxine (FT4) and triiodothyronine (FT3). In contrast, in HT, anti-C1q correlated positively with TSH levels. No correlation between TSH and thyroid autoantibodies was found. In conclusion, we found an increased prevalence of anti-C1q in patients with AITD and their levels correlated with the thyroid function in both GD and HT. This correlation seems to be independent of thyroid autoantibodies. Therefore, anti-C1q might point to a pathogenic mechanism involved in the development of AITD that is independent of classical thyroid autoantibodies.
Depressed activation of the lectin pathway of complement in hereditary angioedema
Authors: Varga L , Széplaki G , Laki J , Kocsis A , Kristóf K , Gál P , Bajtay Z , Wieslander J , Daha M R , Garred P , Madsen H O , Füst G , Farkas H 
Published: October 2008

Summary
The possibility of simultaneous measurement of the classical pathway (CP), mannan-binding lectin (MBL)–lectin pathway (LP) and alternative pathway (AP) of complement activation by the recently developed Wielisa method allowed us to investigate the in vivo significance of the C1-inhibitor (C1INH) in three complement activation pathways. Functional activity of the CP, LP and AP were measured in the sera of 68 adult patients with hereditary angioedema (HAE) and 64 healthy controls. In addition, the level of C1q, MBL, MBL-associated serine protease-2 (MASP-2), C4-, C3- and C1INH was measured by standard laboratory methods. MBL-2 genotypes were determined by polymerase chain reaction. Besides the complement alterations (low CP and C1INH activity, low C4-, C1INH concentrations), which characterize HAE, the level of MASP-2 was also lower (P = 0·0001) in patients compared with controls. Depressed LP activity was found in patients compared with controls (P = 0·0008) in homozygous carriers of the normal MBL genotype (A/A), but not in carriers of variant genotypes (A/O, O/O). Activity of CP correlated with LP in patients (Spearman's r = 0·64; P &lt; 0·0001), but no significant correlation was found in the control group and no correlation with AP was observed. In contrast, the activity of CP and AP correlated (Spearman's r = 0·47; P &lt; 0·0001) in healthy controls, but there was no significant correlation in the HAE patients. We conclude that the activation of LP might also occur in subjects with C1INH deficiency, which is reflected by the low MASP-2 and C4 levels.
Differential patterns of endothelial and leucocyte activation in ‘typhus-like’ illnesses in Laos and Thailand
Authors: Paris D H , Jenjaroen K , Blacksell S D , Phetsouvanh R , Wuthiekanun V , Newton P N , Day N P J , Turner G D H 
Published: October 2008

SummaryScrub typhus is responsible for a large proportion of undifferentiated fevers in south-east Asia. The cellular tropism and pathophysiology of the causative agent, Orientia tsutsugamushi, remain poorly understood. We measured endothelial and leucocyte activation by soluble cell adhesion molecule enzyme-linked immunosorbent assays in 242 Lao and Thai patients with scrub or murine typhus, leptospirosis, dengue, typhoid and uncomplicated falciparum malaria on admission to hospital. Soluble E-selectin (sE-selectin) levels were lowest in dengue, sL-selectin highest in scrub typhus with a high sE-selectin to sL-selectin ratio in leptospirosis patients. In scrub typhus patients elevated sL-selectin levels correlated with the duration of skin rash (P = 0·03) and the presence of eschar (P = 0·03), elevated white blood cell (WBC) count (P = 0·007), elevated lymphocyte (P = 0·007) and neutrophil counts (P = 0·015) and elevated levels of sE-selectin correlated with the duration of illness before admission (P = 0·03), the presence of lymphadenopathy (P = 0·033) and eschar (P = 0·03), elevated WBC (P = 0·005) and neutrophil counts (P = 0·0003). In comparison, soluble selectin levels in murine typhus patients correlated only with elevated WBC counts (P = 0·03 for sE-selectin and sL-selectin). Soluble intercellular adhesion molecule-1 and soluble vascular adhesion molecule-1 levels were not associated significantly with any clinical parameters in scrub or murine typhus patients. The data presented suggest mononuclear cell activation in scrub typhus. As adhesion molecules direct leucocyte migration and induce inflammatory and immune responses, this may represent O. tsutsugamushi tropism during early dissemination, or local immune activation within the eschar.
(GT)n Dinucleotide repeat polymorphism of haem oxygenase-1 promotor region is not associated with inflammatory bowel disease risk or disease course
Authors: Hausmann M , Paul G , Kellermeier S , Frey I , Schölmerich J , Falk W , Menzel K , Fried M , Herfarth H , Rogler G 
Published: October 2008

Summary
Haem oxygenase-1 (HO-1) up-regulation was suggested to reduce mucosal tissue damage in inflammatory bowel disease (IBD) and an up-regulation of HO-1 expression in patients with Crohn's disease (CD) and ulcerative colitis (UC) was demonstrated. A HO-1 gene promoter microsatellite (GT)n dinucleotide repeat polymorphism was associated with regulation of HO-1 in response to inflammatory stimuli. We therefore hypothesized that IBD patients might segregate into phenotypes with high or low HO-1 inducibility. Ethylenediamine tetraacetic acid blood samples were obtained from 179 CD patients, 110 UC patients and 56 control patients without inflammation. Genomic DNA was purified and the 5′-flanking region of the HO-1 gene containing the (GT)n dinucleotide repeat was amplified. Polymerase chain reaction (PCR) products were purified and the length of the PCR fragments was analysed. The number of (GT)n repeats in the population studied ranged from 13 to 42. The distribution of the allele frequencies was comparable in patients and controls for both the short and the long alleles. The frequencies of short-, middle- and long-sized alleles were not changed among the groups studied. No correlation was found between IBD and microsatellite instability detected in five individals. Our data indicate that (GT)n dinucleotide repeats of the HO-1 promotor region have no significance for the pathophysiology and disease course of IBD.
Intracellular calcium signalling patterns reflect the differentiation status of human T cells
Authors: Arrol H P , Church L D , Bacon P A , Young S P 
Published: October 2008

SummaryStimulation of T lymphocytes results in the calcium-dependent activation and repression of a large number of genes. However, the functional response made by different T cell subsets is heterogeneous, as their differentiation results in alterations in their sensitivity to activation and in the secretion of cytokines. Here we have investigated the patterns of calcium responses in CD4 and CD8 T cell subsets to help explain their different responses to activation. CD4+ CD45RA+ T cells isolated freshly from human blood gave a sustained calcium signal after stimulation, but this was smaller than elicited in CD4+ CD45RO+ cells. On in vitro differentiation of CD4+ CD45RA+ cells to CD45RO+, the level of the cytoplasmic calcium response rose initially, but then declined steadily during further rounds of differentiation. The proportion producing an oscillatory calcium response or not responding was increased and differentiation was accompanied by a shift in the calcium between intracellular pools. CD8+ T cells gave a smaller calcium response than paired CD4+ T cells and showed a difference in the numbers of cells giving a transient, rather than sustained, calcium signal. The increase in oscillating cells in the CD4+ CD45RO+ population may reflect the heterogeneity of this population, particularly in terms of cytokine production. The changing patterns of calcium responses in T cells as they differentiate may explain variation in the cellular response to activation at different stages in their lifespan and emphasize the importance of the both the quantity and the quality of the calcium signal in determining the outcome of T cell activation.
Pharmacological targeting of C5a receptors during organ preservation improves kidney graft survival
Authors: Lewis A G , Köhl G , Ma Q , Devarajan P , Köhl J 
Published: October 2008

SummaryCadaveric renal transplants suffer frequently from delayed graft function, which is associated with increased risk for long-term graft survival loss. One-third of kidney grafts that are stored in current organ preservation solutions experience delayed graft function, demonstrating the urgent need for improvement. Although ischaemic graft injury is complex in nature, complement activation is considered important to the process. Here we show that pharmacological targeting of the complement 5a receptor (C5aR) during cold ischaemia has a protective effect on early kidney graft survival, inflammation and apoptosis in a mouse model of syngeneic kidney transplantation. Graft survival of kidneys that were stored in University of Wisconsin solution in the presence of a C5aR antagonist increased from 29% to 57%. Increased graft survival was associated with less tubular damage and apoptosis, protection from sustained C5aR expression and decreased production of tumour necrosis factor-α and macrophage inflammatory protein-2. In a translational approach, we determined C5aR expression in paediatric living-related and cadaveric allografts. C5aR expression was significantly higher in all compartments of kidneys from cadaveric compared with kidneys from living-related donors. C5aR expression in cadaveric kidneys correlated positively with cold ischaemia time, renal dysfunction and the frequency of apoptotic tubular cells, suggesting a novel role for C5a in delayed graft function pathogenesis. Supplementing organ preservation solutions with C5aR inhibitors may improve early graft function following cadaveric kidney transplantation.