bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial cell-binding activity of anti-U1-ribonucleoprotein antibodies in patients with connective tissue diseases
Authors: Okawa-Takatsuji M , Aotsuka S , Uwatoko S , Takaono M , Iwasaki K , Kinoshita M , Sumiya M 
Published: March 2003

SummaryIn order to elucidate the immunological properties of anti-U1-ribonucleoprotein (RNP) antibody, one of the autoantibodies detected in patients with connective tissue diseases (CTDs), we tested the endothelial cell-binding by anti-U1-RNP antibodies and epitopes on human pulmonary artery endothelial cells (HPAECs) to which the autoantibody bound. IgG fractions positive for anti-U1-RNP from patients with CTDs bound to the HPAECs. Furthermore, intact and F(ab′)2 IgG anti-U1-RNP purified by affinity chromatography also bound to endothelial cells. The binding activity of IgG fractions positive for anti-U1-RNP to the endothelial cells could be effectively absorbed by U1-RNP-Sepharose. An immunoblotting assay of purified IgG anti-U1-RNP antibodies showed that these antibodies could bind to various membrane proteins of NP40-treated HPAECs such as 68, 48, 43, 38, 33, 29, 28 and 24 kDa. Some bands, 68, 33, 28 and 24 kDa, seemed to correspond to components of U1-RNP, i.e. 68 kDa, A, B′ and C peptides, respectively. We confirmed that the anti-U1-RNP antibody from patients with CTDs can directly recognize a variety of antigens on the endothelial surface of the pulmonary artery, including the components of U1-RNP or other unknown polypeptides. These results suggest that binding to pulmonary artery endothelial cells of this autoantibody may be one of the triggers of endothelial cell inflammation in CTDs.
CD4 T cell recovery is slower in patients experiencing viral load rebounds during HAART
Authors: Scott-Algara D , Aboulker J-P , Durier C , Badell E , Marcellin F , PRUD'Homme M , Jouanne C , Meiffredy V , Brun-Vezinet F , Pialoux G , Raffi F 
Published: March 2003

SummaryTo determine whether viral load rebounds during HAART impact on CD4+ T cell recovery and immune reconstitution, we studied a prospective cohort of 355 antiretroviral naive patients enrolled to be randomized in a trial of three strategies of induction/maintenance HAART. The extent of immune reconstitution in blood through 72 weeks of antiretroviral treatment was evaluated. Lymphocyte subset markers (CD4, CD8, CD45RA, CD62L, CD16, CD19), activation markers (HLA-DR, CD38, CD25) were performed by cytometry analysis. Our results showed that plasma HIV-1 RNA was suppressed to below 500 copies per ml through week 72 in 240 patients (group 1) while the remaining 115 patients experienced at least one viral rebound (group 2). At baseline, CD4 cell count was higher and HIV-1 RNA was lower in group 1 than in group 2. Over 72 weeks, mean increase in CD4+ T cell count was 0·32 cell/mm3/day in group 1 and only 0·14 cell/mm3/day in group 2 (P &lt; 0·0001). However, the patterns of changes in CD4+ and CD8+ T cell subsets during therapy were very similar across the two groups with only subtle and very limited differences. We conclude that permanent control of HIV replication could be necessary for faster immune reconstitution.
Accelerating the induction of Fas-mediated T cell apoptosis: a strategy for transplant tolerance?
Authors: Carroll H P , Ali S , Kirby J A 
Published: March 2003

SummaryAcute allograft rejection is primarily a consequence of clonal expansion of donor-specific T cells with specificity for donor antigen. Immunosuppression current involves the administration of toxic drugs that limit lymphoproliferation, but this treatment is not antigen-specific and allows opportunistic infection. An ideal strategy would be production of donor-specific T cell tolerance in the presence of an otherwise intact and functional T cell repertoire. Methods to enhance normal apoptotic clearance of activated T cells might contribute to development of this state. This study focuses on manipulation in vitro of Fas-mediated T cell apoptosis and compares two methods to enhance the extent and kinetics for clearance of activated T cells. First, the CD4 coreceptor was cross-linked in the presence and absence of Fas-stimulation. It was found that CD4 cross-linking potently induced apoptosis, even in the absence of Fas stimulation. Resting and activated T cells were susceptible to this treatment, precluding the development of antigen-specific tolerance after T cell activation. In a second system, T cells were treated with two staurosporine analogues, Bisindolylmaleimide (Bis) III and VIII and apoptosis was induced by stimulation of Fas. Resting T cells remained resistant to Fas-mediated apoptosis, but treatment of mitogen or alloantigen-activated cells with either Bis III or VIII caused a synergistic increase in apoptosis. These agents also reduced the period of resistance to Fas-mediated apoptosis after T cell activation, possibly by reducing expression of c-FLIP, allowing early activation of caspase 8 in alloreactive T cells. Development of this strategy might provide a route to the induction of specific tolerance after organ transplantation.
Recognition of the 60 kilodalton cysteine-rich outer membrane protein OMP2 by CD4+ T cells from humans infected withChlamydia trachomatis
Authors: Goodall J C , Beacock-Sharp H , Deane K H O , Gaston J S H 
Published: March 2003

SummaryT cell-mediated immunity is important in the control of chlamydia infection but chlamydia-specific T cells are also implicated in the inflammation and tissue damage which characterize chlamydia associated diseases. To investigate target antigens of the T cell-mediated immune response to chlamydia infection, Chlamydia trachomatis-specific CD4+ T cell clones were isolated from a patient with chlamydia-induced reactive arthritis. T cell immunoblotting indicated that an antigen of ∼60 kilodaltons molecular mass was recognized, and recombinant 60 kilodalton cysteine-rich outer membrane 2 (OMP2) proved to be stimulatory. By using deletion constructs and synthetic peptides an epitope presented by HLA-DRB1*0401 was defined and proved to contain the nonamer peptide within the OMP2 sequence predicted to have the greatest binding affinity for DRB1*0401 The sequence of the epitope is conserved in all C. trachomatis strains but not in C. pneumoniae. Investigation of patients with acute urethritis and additional patients with sexually acquired reactive arthritis showed that OMP2-reactive T cells were readily detectable in peripheral blood and synovial fluid. Thus OMP2 is a target antigen of the T cell-mediated immune response to CT infection.
Proliferation of T-cell subsets that contact tumour cells in colorectal cancer
Authors: Golby S J C , Chinyama C , Spencer J 
Published: March 2003

SummaryWe have investigated the proliferation rates of T-cell subsets in colorectal carcinomas using immunohistochemistry. It was found that the tumour-infiltrating T cells in contact with the tumour cells have a significantly higher frequency of proliferation than those in the stroma. In particular, the CD8+ intraepithelial lymphocytes (T-IEL) within the tumours have a significantly higher frequency of proliferation in comparison with CD8+ T cells in the stromal compartment or in any normal mucosal lymphoid tissues. It is possible that the proliferation of the CD8+ T-IEL may be driven by self-antigens expressed on the tumour cells. The proportion of CD3+ CD7– T cells is increased within carcinomas compared with the normal colon, and a population of CD57+ T cells was observed which is absent from the normal colon. It is possible that these phenotypes are acquired in situ due to repeated stimulation of the T cells by tumour antigens. Intact colorectal carcinoma explants were cultured, and the presence of tumour-infiltrating T cells analysed after 3 days of culture in isolation from the systemic compartments. CD3+ T cells were proliferating (at a low rate) within the explants after 3 days of culture, indicating that they may be sustained by factors present in the tumour microenvironment.
Is ageing associated with a shift in the balance between Type 1 and Type 2 cytokines in humans?
Authors: Sandmand M , Bruunsgaard H , Kemp K , Andersen-Ranberg K , Pedersen A N , Skinhøj P 
Published: March 2003

SummaryThe balance between Type 1 and Type 2 cytokines is important for the outcome of several infectious diseases. As elderly humans show increased morbidity and mortality from infectious diseases, this study tests if ageing is associated with a change towards Type 2 dominance in T cells. Expression of IFN-γ, and IL-4 was measured in CD4+ and CD8+ T cells by flow cytometry in three groups: young controls (n = 28), 81-year-olds (n = 22), and centenarians (n = 25). The major findings were that the percentage of IFN-γ+ as well as IL-4+ T cells was increased in aged subjects. Furthermore, after adjusting for decreased lymphocyte counts in the elderly, the concentration in the blood of IFN-γ+ and IL-4+ CD8+ T cells was still increased in the 81-year-olds. In centenarians, a shift towards a relative dominance of Type 2 cytokine expression was found within CD8+ T cells. Furthermore, the percentage of T cells with cytokine expression was closely correlated to the in vivo expression of CD95 and CD45RO. In conclusion, we found some evidence for an age-related shift towards a Type 2 cytokine profile.
Expression of eotaxin, an eosinophil-selective chemokine, parallels eosinophil accumulation in the vesiculobullous stage of incontinentia pigmenti
Authors: JEAN-BAPTISTE S , O'TOOLE E A , CHEN M , GUITART J , PALLER A , CHAN L S 
Published: March 2003

SUMMARYIncontinentia pigmenti (IP) is an X-linked dominant genodermatosis primarily affecting female children. The initial vesiculobullous stage of IP is characterized clinically by inflammatory papules, blisters, and pustules, and histopathologically by acanthosis, keratinocyte necrosis, epidermal spongiosis and massive epidermal eosinophil infiltration. The cause of this multisystem disease is attributed to the mutations of an X-linked regulatory gene, termed nuclear factor-κB essential modulator (NEMO). The exact mechanism of epidermal eosinophil accumulation has not yet been determined. We explored the possible role of an eosinophil-selective, nuclear factor-κB-activated chemokine, eotaxin, in the accumulation of eosinophils in the initial stage of the disease. Monoclonal antibody (6H9) specific for human eotaxin strongly labelled the suprabasal epidermis of IP skin, paralleling the upper epidermal accumulation of eosinophils, but did not label the epidermis of normal skin or lesional skin from patients with other inflammatory skin diseases not characterized by prominent eosinophil accumulation, namely dermatitis herpetiformis and selected cases of atopic dermatitis lacking significant numbers of eosinophils. In addition, endothelial cells in lesional skin of IP also exhibited strong expression of eotaxin, which correlated with perivascular and intravascular eosinophil infiltration. We also examined the in vitro effects on epidermally derived eotaxin of several cytokines that were nuclear factor-κB-activated and/or known to induce eotaxin expression. In normal human keratinocytes, proinflammatory cytokines either independently (IL-1α) or synergistically (tumour necrosis factor-alpha (TNF-α)/ interferon-gamma (IFN-γ) and TNF-α/IL-4) up-regulated eotaxin expression. These studies suggest that release of cytokines during the initial inflammatory stage of IP induces epidermal expression of eotaxin, which may play a role in the epidermal accumulation of eosinophils.
Local immunostimulation induced by intravesical administration of autologous interferon-gamma-activated macrophages in patients with superficial bladder cancer
Authors: PAGÈS F , LEBEL-BINAY S , VIEILLEFOND A , DENEUX L , CAMBILLAU M , SOUBRANE O , DEBRÉ B , TARDY D , LEMONNE J-L ROMET , ABASTADO J-P , FRIDMAN W-H , THIOUNN N 
Published: March 2003

Summary
We conducted a phase I/II clinical trial of the safety and efficacy of intravesical administration of autologous IFN-γ-activated macrophages (MAK) in patients with superficial bladder cancer. Monocyte-derived MAK cells were prepared in vitro and patients received six instillations of 1·4 × 108 to 2·5 × 108 cells, once a week, for five consecutive weeks. Treatment was well tolerated, with seven grade 1 and five Grade 2 protocol-related adverse effects. Nine out of 17 included patients had no recurrences during the year following the first instillation of MAK. The aim of the present study was to search for immune parameters related to local immunostimulation induced by MAK. Monitoring of the patients showed that urinary IL-8, GM-CSF and, to a lesser extent, IL-18 were increased following MAK instillations, with inter-individual differences. The urinary IL-8 level was about 10-fold higher than that observed for other cytokines, and its biological activity was reflected by a concomitant increase of urinary elastase, indicating neutrophil activation and degranulation. We also showed that nine out of 12 patients investigated presented an increase of urinary neopterin, a marker of IFN-γ-activated macrophages, 7 days after MAK instillation, while serum neopterin levels were almost stable. These results are in line with persistence of activated macrophages in the bladder wall after infusions. Moreover, there was evidence of macrophages in urine smears 2 months after the sixth MAK instillation, and the score of macrophages correlated with the quantity of neutrophils in the urine. Overall, this study provides evidence of a local immunostimulation induced by this novel and safe immunotherapeutic approach of MAK instillations in patients with superficial bladder cancer.
Expression and functional activity of CXCR-4 and CCR-5 chemokine receptors in human thymocytes
Authors: ZAMARCHI R , ALLAVENA P , BORSETTI A , STIEVANO L , TOSELLO V , MARCATO N , ESPOSITO G , RONI V , PAGANIN C , BIANCHI G , TITTI F , VERANI P , GEROSA G , AMADORI A 
Published: March 2003

SummaryIn this paper we addressed the expression of the HIV co-receptors CXCR-4 and CCR-5 in human thymocytes by phenotypic, molecular and functional approaches. Cytofluorimetric analysis disclosed that CXCR-4 was constitutively expressed by freshly isolated thymocytes (~10 000 molecules/cell in about 30% of thymocytes); the receptor was endowed with functional activity, as it mediated polarization, migration and intracellular Ca2+ increase in response to its ligand, SDF-1. On the contrary, CCR-5 expression in freshly isolated thymocytes was significantly lower (&lt;4000 molecules/cell in less than 5% of the cells), and no functional response to CCR-5 agonists could be documented. Northern blot analysis of freshly isolated thymocytes showed high CXCR-4 mRNA levels, whereas the message for CCR-5 was barely detectable. On the other hand, a modest increase in the expression of CCR-5 was associated with in vitro thymocyte stimulation, and CCR-5 density at the cell surface attained CXCR-4 figures in most cases. None the less, no functional response to CCR-5 agonists could be documented in in vitro stimulated thymocytes. In vitro infection of thymocytes by CAT-expressing recombinant HIV bearing the envelope glycoproteins from different isolates showed that T-tropic strains, which use CXCR-4 as a co-receptor, were more efficient in infecting thymocytes than M-tropic strains, which preferentially use CCR-5. Altogether, these data indicate that expression of the major co-receptors involved in infection by M-tropic HIV strains is very poor in human thymocytes, and would suggest that thymocyte infection by M-tropic HIV strains may be a rare event in vivo.
Feeding NOD mice with pig splenocytes induces transferable mechanisms that modulate cellular and humoral xenogeneic reactions against pig spleen or islet cells
Authors: YOU S , GOUIN E , SAÏ P 
Published: March 2003

SUMMARYWe have reported previously that oral administration of pig cells to NOD mice modified xenogeneic cellular response against pig islet cells (PICs), and hypothesized that it may have induced active suppression. This preliminary report evaluated only the effect of feeding pig cells by ‘primary’ proliferation, i.e. when splenocytes from fed mice are confronted with pig cells in vitro. The present study also considered ‘secondary’ proliferation and cytokine production after feeding and subsequent in vivo graft of pig cells. Additionally, serum IgM and IgG isotypes were quantified by ELISA using pig target cells. Induction of active mechanism by feeding was hypothetical, which led us here to transfer splenocytes from mice fed pig spleen cells (PSC) and evaluate ‘primary’ (after transfer) and ‘secondary’ (after transfer and subsequent graft of pig cells) proliferations and cytokine secretions in recipient mice. We also determined whether the effects of feeding pig cells persisted after depression of suppressor mechanisms by cyclophosphamide. Mice fed with PSC displayed increased ‘primary’ splenocyte proliferation to PSC or PIC (P &lt; 0·0001), while ‘secondary’ responses were decreased (P &lt; 0·03) in those fed PSC and subsequently grafted with PSC. The increased ‘primary’ and decreased ‘secondary’ proliferations were reduced (P &lt; 0·04) by pretreatment with cyclophosphamide. The IL-10/ and IL-4/IFNγ ratios produced in response to PSC increased (P &lt; 0·04) in mice fed and grafted with PSC compared to those grafted only with PSC. IgM and IgG levels against pig cells were, respectively, increased (P &lt; 0·04) and decreased (P &lt; 0·04) in mice fed and grafted with PSC. IgG2a and IgG2b, but not IgG1, levels were lower (P &lt; 0·01). These effects of feeding PSC on ‘secondary’ proliferation, cytokine and antibody productions, were not detected when mice were fed PSC only after graft with PSC. Transfer with splenocytes from mice fed PSC increased ‘primary’ proliferation of splenocytes from recipient mice in response to PSC (P &lt; 0·02) or PIC (P &lt; 0·05). After transfer with splenocytes from PSC-fed mice and graft with PSC, ‘secondary’ proliferation to pig cells were reduced (P &lt; 0·04), and the IL-10/IFNγ ratio produced in response to PSC was increased fourfold. Thus, oral administration of PSC induces active transferable mechanisms, characterized by a biphasic pattern with early increased ‘primary’ xenogeneic cellular reactions to both PSC and PIC, followed by decreased ‘secondary’ responsiveness and a concomitant shift of the Th1/Th2 balance towards greater Th2 influence. Decreased responsiveness may be due to active suppression, even though induction of anergy or deletion cannot be excluded.
High levels of inflammatory cytokines are associated with poor clinical response to steroid treatment and recurrent episodes of type 1 reactions in leprosy
Authors: MANANDHAR R , SHRESTHA N , BUTLIN C R , ROCHE P W 
Published: March 2003

SUMMARYLevels of leprosy antigen-induced interferon-gamma (IFN-γ), tumour necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) were measured in 96 leprosy patients with type 1 reactions (T1R) before, during and after a standard 12-week course of steroids. Peripheral blood mononuclear cells (PBMC) from leprosy patients with untreated T1R produced significantly more TNF-α than leprosy patients without T1R. Median levels of IFN-γ and TNF-α in T1R patients fell during treatment with steroids; however, TNF-α levels increased as the steroid dose was reduced. Median IL-10 levels increased throughout the steroid treatment period and were associated strongly with TNF-α levels. Patients with high cytokine levels had a poorer recovery of sensory or voluntary muscle nerve function, a higher risk of reactivation of symptoms during steroid treatment, and a higher risk of another episode of T1R within 2 months of completing the steroid regimen. Rapid and effective reversal of the inflammatory process in T1R is critical to prevent permanent nerve damage from T1R and monitoring cytokine levels during treatment may be useful.
Ganglioside expression in tissues of mice lackingβ2-microglobulin
Authors: MARKOTIC´ A , MARUSˇIC´ A , TOMAC J , MUüTHING J 
Published: March 2003

SUMMARYThis study presents a comparative analysis of gangliosides from lymphoid (spleen and thymus) and other (brain, liver, lungs and muscle) tissues of C57BL/6 mice lacking the gene for β2-microglobulin (β2M), a constitutive component of the MHC class I molecule. Ganglioside fractions in the tissues of mice homozygous (β2M−/−) and heterozygous (β2M−/+) for the gene deletion were determined by high performance thin-layer chromatography (HPTLC), followed by immunostaining with specific polyclonal antibodies. Ubiquitous gangliosides GM3(Neu5Ac) and GM3(Neu5Gc) were the dominant gangliosides in the lungs of the control β2M−/+ mice, whereas the homozygous knockout mice had substantially decreased expression of these structures. The lungs of the β2M−/− mice also had reduced expression of T-lymphocyte-specific GM1b-type gangliosides (GM1b and GalNAc-GM1b). β2M-deficient mice also had more GM1a and GD1a gangliosides in the liver, and several neolacto-series gangliosides were increased in the brain and lungs. This study provides in vivo evidence that the β2M molecule can influence the acquisition of a distinct ganglioside assembly in different mouse organs, implicating its non-immunological functions.
IgA autoreactivity: a feature common to inflammatory bowel and connective tissue diseases
Authors: KAZEMI-SHIRAZI L , GASCHE C H , NATTER S , GANGL A , SMOLEN J , SPITZAUER S , VALENT P , KRAFT D , VALENTA R 
Published: March 2003

SUMMARYThe immunopathogenic mechanisms in inflammatory bowel disease (IBD) are not yet fully established. The aim of this study was to determine the profile and magnitude of IgA and IgG autoantibodies in IBD patients. The autoantigen profile defined by IgA and IgG antibodies from 24 IBD (14 Crohn's disease CD], 10 ulcerative colitis UC]), three coeliac, 12 connective tissue disease (CTD) patients and 10 healthy individuals was studied in human cellular extracts by Western blotting. The magnitude of the IgA and IgG1-4 subclass responses was measured by ELISA. IBD patients could not be distinguished from healthy individuals on the basis of IgG autoantibodies to Western blotted proteins. IgG subclass analysis indicated no clear bias towards Th1 or Th2 immune responses in IBD or CTD. In accordance with previous work, we found that IgA autoreactivity was strongest in coeliac disease patients. Unexpectedly, IBD as well as CTD patients exhibited strong IgA autoantibody reactivities to components of similar molecular weights (16–80 kD) in intestinal and non-intestinal epithelial cell lines. Our data indicate immunopathogenic similarities between IBD and CTD.