bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of circulating soluble CD28 in patients with systemic lupus erythematosus, primary Sjögren's syndrome and systemic sclerosis
Authors: HEBBAR M , JEANNIN P , MAGISTRELLI G , HATRON P-Y , HACHULLA E , DEVULDER B , BONNEFOY J-Y , DELNESTE Y 
Published: April 2004

SUMMARYThe aim of this study was to evaluate the presence and the role of the serum soluble costimulatory molecule CD28 in patients with systemic lupus erythematosus (SLE), primary Sjögren's syndrome (SS), and systemic sclerosis (SSc). Soluble CD28 concentration was determined by ELISA in 45 patients with SLE, 45 patients with primary SS, 30 patients with SSc, and 45 healthy subjects. We also evaluated CD28 mRNA expression by semiquantitative RT-PCR, and the biological activity of recombinant soluble CD28 on T lymphocyte activity. Concentrations of soluble CD28 were significantly higher in patients with SLE, primary SS and SSc than in healthy subjects. Soluble CD28 concentrations were higher in patients with systemic primary SS than in patients with glandular-limited primary SS. PCR analysis suggested that soluble CD28 resulted from the shedding of the membrane form. In vitro assay revealed that soluble CD28 inhibits the anti-CD3 mAb induced T cell proliferation. Soluble CD28, which modulates the proliferation of T lymphocytes, could be associated with disease severity in patients with autoimmune disease, especially primary SS. These results suggest that soluble CD28 could play an important role in the regulation of autoimmune diseases.
Neutrophils migrate across intestinal epithelium usingβ2 integrin (CD11b/CD18)-independent mechanisms
Authors: BLAKE K M , CARRIGAN S O , ISSEKUTZ A C , STADNYK A W 
Published: April 2004

SUMMARYRecruitment of polymorphonuclear leucocytes (PMN) across the intestinal epithelium is dependent on specific adhesion molecules and chemoattractants diffusing from the intestinal lumen. The present understanding is that in response to fMLP, PMN migration across a T84 colon carcinoma monolayer is dependent on the β2 integrin, Mac-1 (CD11b/CD18). To further understand PMN transepithelial migration, we sought to determine whether migration to C5a, IL-8 and LTB4 was similarly Mac-1-, or even CD18-dependent. T84 epithelial cell monolayers growing on Transwell filters were used in combination with radiolabelled peripheral blood PMN. The number of migrated PMN was established by the amount of radioactivity recovered from the well after the migration period. Monoclonal antibodies were used to block integrin function. Whereas essentially all migration to fMLP across T84 monolayers was prevented by anti-CD18 antibody, significant migration to C5a, IL-8 or LTB4 persisted despite anti-CD18 antibody, indicating PMN are capable of β2 integrin-independent transepithelial migration. An antibody to CD11b but not CD11a blocked migration to an extent similar as with anti-CD18. CD18-independent PMN migration to C5a occurred only in the basolateral-to-apical direction across epithelial cells. Co-stimulation of PMN with C5a and fMLP or IL-8 plus LTB4 and fMLP still resulted in CD18-independent migration. Thus CD18 use during PMN migration across this model epithelium is a function of the chemoattractant inducing migration. The finding of CD18-independent migration mechanisms needs to be considered when developing antiadhesion molecule strategies to reduce or reverse intestinal inflammation.
The nuclear pore complex protein Tpr is a common autoantigen in sera that demonstrate nuclear envelope staining by indirect immunofluorescence
Authors: OU Y , ENARSON P , RATTNER J B , BARR S G , FRITZLER M J 
Published: April 2004

SUMMARY
We studied the autoantigen targets of 75 human sera that had antibodies to the nuclear envelope (NE) as identified by indirect immunofluorescence (IIF) on HEp-2 cells. Several different IIF staining patterns could be identified when antibodies to different components of the nuclear membrane (NM) and nuclear pore complexes (NuPC) were identified: a smooth membrane pattern characteristic of antibodies to nuclear lamins, a punctate pattern typical of antibodies to the nuclear pore complex and more complex patterns that included antibodies to nuclear and cytoplasmic organelles. Western immunoblotting of isolated nuclear and NE proteins and immunoprecipitation of radiolabelled recombinant proteins prepared by using the full-length cDNAs of the Translocated promoter region (Tpr), gp210 and p62 were used to identify specific autoantibody targets. Fifty-two of the 75 (70%) sera bound to Tpr, 25 (33%) bound to lamins A, B or C, 15 (20%) reacted with gp210 and none reacted with p62. Sixteen (21%) did not react with any of the NE components tested in our assays. The clinical features of 37 patients with anti-NE showed that there were 34 females and three males with an age range of 16–88 years (mean 59 years). The most frequent clinical diagnosis (9/37 = 24%) was autoimmune liver disease (ALD; two with primary biliary cirrhosis), followed by seven (19%) with systemic lupus erythematosus (SLE), four (11%) with a motor and/or sensory neuropathy, three (8%) with anti-phospholipid syndrome (APS), two with systemic sclerosis (SSc), two with Sjögren's syndrome (SjS), and others with a variety of diagnoses. This report indicates that Tpr, a component of the NuPC, is a common target of human autoantibodies that react with the NE.
Differential expression of Toll-like receptor (TLR)-2 and TLR-4 on monocytes in human sepsis
Authors: ARMSTRONG L , MEDFORD A R L , HUNTER K J , UPPINGTON K M , MILLAR A B 
Published: April 2004

SUMMARYToll-like receptors (TLRs) are a recently described family of immune receptors involved in the recognition of pathogen-associated molecular patterns (PAMPs). The central role of TLR-2 and TLR-4 in microbial responses suggests they may be implicated in the pathogenesis of human sepsis. We hypothesized that the incidence and outcome of sepsis would be influenced by the expression of TLR-2 and TLR-4 on monocytes. We have examined the expression of TLR-2 and TLR-4 mRNA and protein and their response to pro- and anti-inflammatory agents on monocytes from subjects in the intensive therapy unit (ITU) with and without Gram-negative, Gram-positive or polymicrobial sepsis. We compared these data to ITU and healthy control subjects. TLR-2 mRNA was significantly up-regulated on monocytes from subjects with both Gram-positive and Gram-negative sepsis. Similarly, we detected increased levels of TLR-2 protein on the surface of monocytes from sepsis subjects relative to ITU controls. TLR-4 mRNA was increased in Gram-positive subjects; however, there was no corresponding increase in TLR-4 protein. Although TLR-4 mRNA expression in healthy control monocytes could be modulated in vitro by culture with lipopolysaccharide or interleukin-10, this was not observed in monocytes obtained from sepsis and ITU control subjects, suggesting that septic and ITU control milieus may alter the immunoregulation of TLR-4 mRNA expression on monocytes. TLR-2 mRNA was not modulated in culture by any stimulus in any group. We suggest that expression and regulatory response of monocyte TLR-2, and to a lesser extent TLR-4 may be abnormal in human sepsis.
The influence of partial or total thymectomy during open heart surgery in infants on the immune function later in life
Authors: EYSTEINSDOTTIR J H , FREYSDOTTIR J , HARALDSSON A , STEFANSDOTTIR J , SKAFTADOTTIR I , HELGASON H , OGMUNDSDOTTIR H M 
Published: April 2004

SUMMARY
Infants undergoing open heart surgery often have all or part of their thymus removed. The activity of the immune system has not been investigated thoroughly in these children, and only shortly after the operation. Therefore, it was decided to investigate the activity of the immune system in more detail in children several years after their operation. Peripheral blood samples from 19 children who had undergone open heart surgery during their first months of life was collected (study group) and from 19 age- and gender-matched children (control group). The activity of the immune system was evaluated by measuring the number of different cell types in peripheral blood, the phenotype of lymphocytes and the response of T cells following in vitro stimulation by mitogen, tetanus toxoid and measles antigen. The study group had significantly lower counts of total lymphocytes, which was reflected in a lower number of T cells but not B cells. Furthermore, the study group had significantly lower proportion of T cells (CD3+) and helper T cells (CD4+), but not cytotoxic T cells (CD8+). The level of neutrophils in peripheral blood was significantly higher in the study group. This may indicate enhanced innate immunity when the acquired immunity is defective. The results indicate a shift to extrathymic T cell maturation, which is less efficient for CD4+ helper cells than for CD8+ cytotoxic cells.
Development of an anti-Salmonella typhi ViELISA: assessment of immunocompetence in healthy donors
Authors: FERRY B L , MISBAH S A , STEPHENS P , SHERRELL Z , LYTHGOE H , BATEMAN E , BANNER C , JONES J , GROOME N , CHAPEL H M 
Published: April 2004

SUMMARYWe have developed a solid-phase enzyme-linked immunosorbent assay (ELISA) to study the vaccination responses to Vi capsular polysaccharide of Salmonella typhi (S. typhi Vi) vaccine. Purified S. typhi Vi polysaccharide was biotinylated and bound to streptavidin coated microtitre plates. Reproducibility was determined across a range of IgG antibody levels: mean interassay coefficients of variation (CVs) were &lt;11·9% for non-vaccinated sera with low levels and &lt;11·1% for sera with very high levels of anti-S. typhi Vi IgG. Specificity was assessed by inhibition studies using salmonella antigen. We have developed the ELISA based on normal adult serum responses to test immunization with S. typhi Vi vaccine. We also report here anti-S. typhi Vi IgG levels in a group of healthy preschool children. In non-vaccinated adult sera (n = 104), the median value of anti-S. typhi Vi IgG, expressed in S. typhi Vi arbitrary units (AU/ml), was 5·3 AU/ml and in non-vaccinated sera from children (n = 44) the median value was 1·4 AU/ml. The data from immunization of healthy volunteers (n = 23) show that geometric mean levels of anti-S. typhi Vi IgG were significantly higher (P &lt; 0·0001) for post-vaccination subjects (39·2 AU/ml) compared to paired prevaccination (3·9 AU/ml) values. A total of 21/23 vaccine recipients had &lt;8 AU/ml S. typhi Vi IgG in their sera prior to vaccination and of these 20/21 (95%) exhibited threefold increases and 14/21 (67%) fourfold increases in their S. typhi Vi IgG following vaccination. Based on the data in this study, we propose a threefold increase in anti-S. typhi Vi IgG post-vaccination to be considered a positive vaccination response. The ability to demonstrate clearly an antibody rise in response to immunization with S. typhi Vi capsular polysaccharide vaccine suggests that this is likely to be a useful vaccine for the assessment of B cell function in patients with suspected immune deficiency.
Phenotypic characterization of regulatory T cells in the human decidua
Authors: HEIKKINEN J , MÖTTÖNEN M , ALANEN A , LASSILA O 
Published: April 2004

SUMMARYPregnancy is a unique situation for the maternal immune system. We have studied and identified a CD4+CD25+ regulatory T (Treg) cell population isolated from the human decidua. This mucosal surface in the uterus is in direct contact with semiallogenic fetal cells. We observed that about 14% of the decidual CD4+ T cells have the CD4+CD25+ phenotype. The decidual CD4+CD25+ T cells expressed high frequency of intracellular CTLA-4 (CTLA-4i). The majority of CD4+CD25+CTLA-4i+ cells were also positive for GITR and OX40, typical markers for human Treg cells. The frequency of CD4+CD25+ T cells in the peripheral blood from pregnant women was found to be increased during the first and second trimester of gestation when compared to nonpregnant controls. Being an important molecule for Treg cells, the role of CTLA-4 in the regulation of indoleamine 2,3-dioxygenase (IDO) expression was also examined. The stimulation with CTLA-4Ig did not increase IDO mRNA expression in CD14+ cells from pregnant women, while IFN-γ was observed to up-regulate IDO expression. The presence of Treg cells in the human decidua suggests that these cells are important in protecting the fetus from alloreactive immune responses at the maternal–fetal interface.
A dominant linear B-cell epitope of ricin A-chain is the target of a neutralizing antibody response in Hodgkin's lymphoma patients treated with an anti-CD25 immunotoxin
Authors: CASTELLETTI D , FRACASSO G , RIGHETTI S , TRIDENTE G , SCHNELL R , ENGERT A , COLOMBATTI M 
Published: April 2004

SUMMARYHodgkin's lymphoma patients treated with an anti-CD25 Ricin toxin A-chain (RTA)-based Immunotoxin (RFT5.dgA) develop an immune response against the toxic moiety of the immunoconjugate. The anti-RTA antibody response of 15 patients showing different clinical features and receiving different total amounts of RFT5.dgA was therefore studied in detail, considering antibody titre, IgG and IgM content, average binding efficacy and ability to inhibit in vitro the cytotoxicity of a RTA-based Immunotoxin. No correlations were found between these parameters and the clinical features of the patients or the total amount of Immunotoxin administered. However, using a peptide scan approach we have identified a continuous epitope recognized by all patients studied, located within the stretch L161-I175 of the RTA primary sequence, close to a previously identified T-cell epitope. The ability of anti-L161-I175 antibodies to recognize folded RTA and to affect the biological activity of RTA by inhibiting RTA-IT cytotoxicity in vitro revealed that they may exert an important role in IT neutralization in vivo. Discovery of RTA immunodominant epitopes which are the target of anti-RTA immune response may lead to the development of immunomodulating strategies and to more successful treatment schedules.
Induction of iNOS expression and antimicrobial activity by interferon (IFN)-β is distinct from IFN-γ in Burkholderia pseudomallei-infected mouse macrophages
Authors: UTAISINCHAROEN P , ANUNTAGOOL N , ARJCHAROEN S , LIMPOSUWAN K , CHAISURIYA P , SIRISINHA S 
Published: April 2004

SUMMARY
Burkholderia pseudomallei is a causative agent of melioidosis. This Gram-negative bacterium is able to survive and multiple inside both phagocytic and nonphagocytic cells. We previously reported that exogenous interferons (both type I and type II) enhanced antimicrobial activity of the macrophages infected with B. pseudomallei by up-regulating inducible nitric oxide synthase (iNOS). This enzyme thus plays an essential role in controlling intracellular growth of bacteria. In the present study we extended our investigation, analysing the mechanism(s) by which the two types of interferons (IFNs) regulate antimicrobial activity in the B. pseudomallei-infected macrophages. Mouse macrophage cell line (RAW 264·7) that was exposed simultaneously to B. pseudomallei and type I IFN (IFN-β) expressed high levels of iNOS, leading to enhanced intracellular killing of the bacteria. However, neither enhanced iNOS expression nor intracellular bacterial killing was observed when the macrophages were preactivated with IFN-β prior to being infected with B. pseudomallei. On the contrary, the timing of exposure was not critical for the type II IFN (IFN-γ) because when the cells were either prestimulated or co-stimulated with IFN-γ, both iNOS expression and intracellular killing capacity were enhanced. The differences by which these two IFNs regulate antimicrobial activity may be related to the fact that IFN-γ was able to induce more sustained interferon regulatory factor-1 (IRF-1) expression compared with the cells activated with IFN-β.
Mannan-binding lectin insufficiency in children with recurrent infections of the respiratory system
Authors: CEDZYNSKI M , SZEMRAJ J , SWIERZKO A S T , BAK-ROMANISZYN L , BANASIK M , ZEMAN K , KILPATRICK D C 
Published: April 2004

SUMMARYBlood samples were collected over a 4-year period from 335 children (aged 1–16 years) suffering from recurrent respiratory infections and 78 controls. The patients were subdivided into four groups: I, children with no immune system defects detected (n = 101); II, children with allergies (n = 94); III, children with humoral response defects (n = 93); and IV, children with disturbances of cellular immunity (n = 66). Nineteen patients had both humoral and cellular abnormalities. All patients and controls were investigated to determine the exon 1 and promoter region variants of the mbl-2 gene. MBL serum concentrations were also determined in samples from 291 patients and 75 controls. The proportion of O (B, D or C) alleles was significantly higher in the patient group compared to controls, and this association was strongest for subgroup III. The promoter LX variant frequency was also commoner in the patients as a whole, and significantly so in subgroups II and IV. Genotypes markedly influenced MBL concentrations in all groups, and correlated with ability to activate the lectin pathway of complement activation. The strongest and most significant inverse correlations between serum MBL and respiratory disease were found in patient group III and in 17 patients with multiple humoral and/or cellular abnormalities. Among nine patients with unexpectedly low LP activity in view of their MBL concentrations, one person was found to be MASP-2 deficient. Our results indicate that mannan-binding lectin insufficiency, with or without a coexisting immune defect, is associated with the occurrence of recurrent respiratory infections in childhood, and this relationship is particularly strong and statistically significant in children with concomitant impairments of humoral immunity.
Corneal stromal cells selectively inhibit production of anti-inflammatory cytokines by activated T cells
Authors: HOLÁŇ V , VÍTOVÁ A , PINDJÁKOVÁ J , KRULOVÁ M , ZAJÍCOVÁ A , FILIPEC M 
Published: April 2004

SUMMARYThe eye has been described as an immunologically privileged site where immunity is purely expressed. It has been demonstrated that administration of antigen into the eye induces only a weak immune response. However, the anterior part of the eye represents an important protective barrier against pathogens and other harmful invaders from the outer environment. Therefore, effective immune mechanisms, which operate locally, need to be present there. Because the cornea has been shown to be a potent producer of various cytokines and other molecules with immunomodulatory properties, we investigated a possible regulatory role for the individual corneal cell types on cytokine production by activated T cells. Mouse spleen cells were stimulated with the T cell mitogen concanavalin A in the presence of either corneal explants or cells of corneal epithelial or endothelial cell lines and the production of T helper 1 (Th1) or Th2 cytokines was determined by enzyme-linked immunosorbent assay (ELISA) or reverse transcription–polymerase chain reaction (RT-PCR). We found that the cornea possesses the ability to inhibit, in a dose-dependent manner, production of the inhibitory and anti-inflammatory cytokines interleukin (IL)-4 and IL-10 by activated T cells. The production of cytokines associated with protective immunity [IL-2, IL-1β, interferon (IFN)-γ] was not inhibited under the same conditions. Corneal explants deprived of epithelial and endothelial cells retained the ability to suppress production of anti-inflammatory cytokines. This suppression was mediated by a factor produced by corneal stromal cells and occurred at the level of cytokine gene expression. We suggest that by this mechanism the cornea can potentiate a local expression of protective immune reactions in the anterior segment of the eye.
Susceptibility of T cell receptor-αchain knock-out mice to ultraviolet B light and fluorouracil: a novel model for drug-induced cutaneous lupus erythematosus
Authors: YOSHIMASU T , NISHIDE T , SEO N , HIROI A , OHTANI T , UEDE K , FURUKAWA F 
Published: April 2004

SUMMARYThe anticancer agent 5-fluorouracil (FU) frequently induces cutaneous lupus erythematosus (LE) lesions on sun exposed sites. Based on this observation, we have tried to establish a cutaneous LE model of C57BL/6 J (B6) mice, B6 T cell receptor (TCR)-α–/– mice and B6 TCR-δ–/– mice treated with FU and/or ultraviolet B light (UVBL) in order to clarify the role of T cells and the cytokine profile of cutaneous lupus lesions. Cutaneous LE-like skin lesions could be induced in TCR-α–/– mice with low FU (0·2 mg) plus UVBL, and in B6 mice treated with a high dose of FU (2·0 mg) plus UVBL. In contrast, low FU plus UVBL induced such skin lesions in TCR-δ–/– mice at a very low incidence. Specifically, the skin lesions of TCR-α–/– mice with low FU plus UVBL appeared more rapidly and were more severe than lesions in B6 mice. The former had the common characteristic features of human chronic cutaneous LE such as typical histology, positive IgG at the dermoepidermal junction, low antinuclear antibody and low mortality. Furthermore, a Th1 response was induced in the development of drug-induced cutaneous LE. FU and UVBL-induced cutaneous LE-like eruption is an excellent model for better understanding the pathomechanisms of skin lesion development in LE.
Protective effect of exogenous recombinant mouse interferon-gamma and tumour necrosis factor-alpha on ectromelia virus infection in susceptible BALB/c mice
Authors: ATRASHEUSKAYA A V , BUKIN E K , FREDEKING T M , IGNATYEV G M 
Published: April 2004

SUMMARY
The resistance to mousepox is correlated with the production of type I cytokines: interleukin (IL)-2, IL-12, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. We intend to describe the modulation of generalized ectromelia virus (EV) infection with exogenous administration of mrIFN-γ and mrTNF-α separately and in combination using susceptible BALB/c mice. The treatment schemes presented resulted in the localization of the generalized EV infection and its development into non-fatal sloughing of the infected limb. This was accompanied by low virus titres in the treated mice due to control of systemic virus replication and virus clearance. The balance of type I versus type II cytokines was dominated by a type I response in the treated groups. The group treated with the combination of IFN-γ and TNF-α exhibited the best survival with Th1-dominant (IFN-γ and IL-12) cytokine profiles, whereas the TNF-α-treated group of mice was less successful in clearance of virus and demonstrated the lowest survival rate. The successful cytokine treatment schemes in this orthopoxvirus model system may have important implications in the treatment of viral diseases in humans and, in particular, of variola virus infection.