bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of CD4+ T helper cells in patients with Kawasaki disease (KD): preferential production of tumour necrosis factor-alpha (TNF-α) by Vβ2− or Vβ8− CD4+ T helper cells
Authors: Sakaguchi M , Kato H , Nishiyori A , Sagawa K , Itoh K 
Published: July 2010

SUMMARYKD is an acute febrile illness in children characterized by coronary arteritis accompanied by aneurysm and thrombotic occlusion. The etiology of KD is unknown. It has been recently reported that KD is associated with the selective expansion of Vβ2+ and Vβ8.1+ T cells in peripheral blood lymphocytes (PBL), by studying the T cell receptor (TCR) repertoire of in vitro activated T cells. KD may therefore be caused by a superantigen [1–3]. To understand better the immunopathology of KD, we investigated TCR Vβ2 and Vβ8.1 expression on both the T cells of freshly isolated PBL and T cell clones (TCC) from patients with KD. Cytokine production by TCC was also studied. Blood samples were obtained from patients with acute (n= 20) and convalescent (n= 20) KD, agematched children with non-infectious diseases (n= 18), and healthy adults (n= 20). Among these four groups, there were no significant differences in the percentages of either Vβ2+ or Vβ8.1+. T cells of freshly isolated PBL. The same was true for the CD4+ or CD8+ T cell subsets. One hundred and five TCC (98 CD3+ CD4+ CD8− and seven CD3+ CDA− CD8+) established from the affected skin, lymph node or PBL of six patients with KD were also negative for either Vβ2 or Vβ8.1 TCR. Sixty-eight of 105 TCC (65%) produced detectable levels (&gt;5 pg/ml) of TNF-α (6–1016 pg/ml), in the absence of any stimuli. In contrast, only 11 (10%) of 105 TCC or 7(7%) of 97 TCC produced detectable levels of IL-2 or IL-6, respectively, in the absence of any stimuli. Stimulation with phytohaemagglutinin (PHA) and phorbol myristate acetate (PMA) induced most TCC to produce higher amounts of TNF-α, IL-2 and IL-6. These results suggest that CD4+ T helper cells expressing TCR-β other than Vβ2 or Vβ8 receptor, primarily through TNF-α production, are involved in the immunopathology of KD.
Passive dual immunization against tumour necrosis factor-alpha (TNF-α) and IL-1β maximally ameliorates acute aminonucleoside nephrosis
Authors: MartÍN A , Molina A , Bricio T , Mampaso F 
Published: July 2010

SUMMARYRats receiving a single dose (10mg/100g) of aminonucleoside of puromycin (PAN) develop heavy proteinuria and acute interstitial nephritis (AIN). Whole isolated glomeruli from rats injected with PAN secreted both TNF-α and IL-1β cytokines. TNF-α secretion was first and maximally detected on day 3, whereas IL-β activity was found on day 7, when rats were heavily proteinuric and AIN developed. In vivo treatment with either anti-TNF-α or anti-IL-1β antibodies produced a drastic and simultaneous reduction in both levels of proteinuria and intensity of interstitial cell infiltrate. These effects improved when both antibodies were administered together. Our studies demonstrate the effectiveness of immunosuppressive therapy against these two cytokines in rats with PAN-induced nephrosis.
Relationship between facilitated allergen presentation and the presence of allergen-specific IgE in serum of atopic patients
Authors: Van Der Heijden F L , Van Neerven R J J , Kapsenberg M L 
Published: July 2010

SUMMARYAllergen presentation to allergen-specific T cells can be facilitated when IgE–allergen complexes are endocytosed by antigen-presenting cells (APC) after binding to the low-affinity Fc·R type II (CD23). Here we present a study on the relative capabilities of sera of atopic patients to mediate facilitated antigen presentation (FAP). To this aim FAP was studied in an in vitro model in which CD23-expressing Epstein–Barr virus (EBV)-B cells act as APC to T lymphocyte clones (TLC) that are specific for Der p 2, a major allergen of housedust mite Dermatophagoides pteronyssinus (Dp). Der p 2 is immune-complexed by preincubation in sera from atopic patients, containing allergen-specific IgE. If EBV-B cells are preincubated with these complexes before using the cells as APC, the allergen-specific TLC proliferate at 100–1000-fold lower allergen concentration than required for T cell activation after presentation of uncomplexed allergen. The relative capability of various sera to mediate FAP was correlated with total serum IgE, and especially with Der p 2-specific serum IgE. In the model used, a high FAP capacity could be demonstrated only in sera with a total serum IgE concentration above approximately 2 /μg/ml or with Der p 2-specific IgE above approximately 100 ng/ml. Maximal FAP, i.e. the ability to induce maximal proliferation of the TLC, was obtained in the presence of more than × 600 ng Der p 2-specific IgE/ml. At 100–600 ng/ml Der p 2-specific IgE the level of FAP was correlated with the concentration of allergen-specific IgE, whereas at lower concentrations FAP was low or absent. All tested sera from eczema patients, all having serum anti-Der p 2-IgE concentrations &gt; 600 ng/ml, showed a high FAP capacity, whereas all tested sera from atopic patients without eczema, which had serum anti-Der p 2-IgE levels &lt; 600 ng/ml, showed no or a low FAP capacity. The association of high FAP capacity with eczema may reflect a functional role of FAP in the pathogenesis of atopic dermatitis.
Anti-La (SS-B) but not anti-Ro52 (SS-A) antibodies cross-react with laminin—a role in the pathogenesis of congenital heart block?
Authors: Li J-M , Horsfall A C , Maini R N 
Published: July 2010

SUMMARYCross-reactions between maternally derived autoantibodies and fetal cardiac antigens have been postulated to play a role in the pathogenesis of congenital heart block (CHB). We have explored the cross-reactivity of autoantibodies to the small ribonuclear autoantigens, La/SS-B and Ro/SS-A, with laminin, the major component of cardiac sarcolemmal membrane using affinity-purified antibodies from patients with Sjögren's syndrome (SS). Anti-La antibodies purified from eight of 10 patients cross-reacted significantly with mouse laminin by ELISA. In contrast, purified antibodies to Ro52 from the same 10 patients showed little or no binding to laminin. Laminin inhibited up to 70% binding of anti-La antibodies to La antigen, and La inhibited up to 65% binding of anti-La antibodies to laminin. The cross-reaction was further examined on cryosections of 10 human fetal hearts aged from 8·7 to 14·9 weeks of gestation, two normal adult hearts, and one pathological adult heart with a diagnosis of dilated cardiomyopathy. Anti-Ro52 antibodies did not bind to the surface of cardiac cells. However, anti-La antibodies from seven of 10 patients tested bound to the surface of fetal myocytes from hearts aged 9·4 to 14·9 weeks of gestation, and also to the myocytes from the pathological adult heart but not to normal adult hearts. Preincubation with La antigen abolished the binding of anti-La antibodies to the surface of adult heart myocytes with dilated cardiomyopathy, and pre-incubation with mouse laminin could partially block this binding. These results suggest that molecular mimicry between laminin and La, but not Ro52, may act as a target for specific maternal autoantibodies, and contribute to the pathogenesis of CHB at a critical stage during fetal cardiac development.
Effect ofMycoplasma arthritidissuperantigen on enzymatically induced arthritis in mice
Authors: Sustackova H , Chambers C A , Hozumi N , Kandel R A , Quinn P A , Cruz T F 
Published: July 2010

SUMMARYThe objective of this study was to examine the effect of the stimulation of the immune system with Mycoplasma arthritidis superantigen (MAS) on joint inflammation and cartilage destruction. MAS was administered either alone or combined with a model of degenerative arthritis induced by intraarticular injection of collagenase enzyme. Intraperitoneal injection of MAS resulted in activation of peripheral lymphocytes in BALB/c mice, as shown by a proliferative response of splenocytes isolated from MAS-treated animals to IL-2-containing supernatant. Intraperitoneal or intraarticular administration of MAS alone at concentrations maximally activating lymphocytes had no detectable effect on joints. Intraarticular injection of collagenase resulted in some infiltration of inflammatory cells into the joints, hyperplasia and hypertrophy of synovial lining, pannus formation and surface loss of proteoglycans 7 days following the injection. At 21 days, the animals showed almost total loss of cartilage and minimal or no inflammation. Animals receiving MAS in addition to collagenase treatment showed similar changes in the joints. These data have demonstrated that activation of the immune system with MAS in vivo does not increase joint inflammation or cartilage degradation in enzymatically induced arthritis.
Antigen-presenting cells in human cutaneous leishmaniasis due toLeishmania major
Authors: Elhassan A M , Gaafar A , Theander T G 
Published: July 2010

SUMMARYIn this study biopsies from skin lesions and draining lymph nodes of patients suffering from cutaneous leishmaniasis caused by Leishmania major were examined by immunohistochemistry, and by light and electron microscopy to identify the types of antigen-presenting cells (APC) and their location. APC, identified morphologically and by their expression of specific cell markers, included Langerhans cells, macrophages, follicular dendritic cells, and interdigitating reticulum cells of the paracortex of lymph nodes. These cells expressed MHC class II antigens and contained Leishmania antigen. Since some keratinocytes and endothelial cells also showed these characteristics, they may also act as APC. By examining tissue samples from skin lesions and draining lymph nodes it was possible to follow the probable route of trafficking of various inflammatory cells between the skin lesion and lymph nodes. Leishmania antigen containing Langerhans cells were found in the epidermis, dermis and the regional lymph nodes. We believe these cells translocate from the epidermis to the dermis, where they take up antigen and migrate to the paracortex of the regional lymph nodes. There they are intimately associated with cells of the paracortex, and could be involved in the generation of Leishmania-specific T memory cells. LFA-1 -positive T cells of the CD45RO phenotype were found in the skin lesion. Venular endothelium in the skin lesions expressed intercellular adhesion molecule-1 (ICAM-1), which is the ligand for LFA-1. The migration of lymphocytes from the vascular lumen to the site of inflammation is possibly a result of the interaction of these two adhesion molecules.
Attenuation of immune complex nephritis in NZB/WF1 mice by a prostacyclin analogue
Authors: Utsunomiya Y , Ogura M , Kawamura T , Mitarai T , Maruyama N , Sakai O 
Published: July 2010

SUMMARY
Although prostaglandins have been shown to inhibit the evolution of the nephritis in NZB/W mice, the mechanisms of this effect are unknown. To characterize such inhibition, we injected the prostacyclin (PGI2) analogue, beraprost, into NZB/W mice, using 0·5mg, 1·0mg or 5·0mg beraprost/kg body weight of test animals three times in 1 week when the mice were 2 months old. Evaluation included measurement of urine albumin excretion, serological parameters and splenic T cell subset, as well as examination of renal histology by light and fluorescence microscopy. Mice given beraprost showed a marked decrease in urine albumin excretion and in glomerular hypercellularity compared with untreated controls. Maximal beneficial effects occurred when the dose was 5·0mg/kg of beraprost. These effects correlated with a reduction of immune complex deposition in glomeruli. In addition, beraprost reduced serum levels of immunoglobulins and anti-double-stranded DNA antibodies, and decreased the number of helper (L3T4+) T cells in splenocytes. These results indicate that beraprost attenuates the nephritis of NZB/W mice, and that the source of this effect is the reduced production of autoantibodies and deposition of immune complexes in glomeruli.
Defective expression of early activation genes in cartilage-hair hypoplasia (CHH) with severe combined immunodeficiency (SCID)
Authors: Castigli E , Irani A-M , Geha R S , Chatila T 
Published: July 2010

SUMMARYCartilage-hair hypoplasia (CHH) is an autosomal recessive disease of unknown etiology characterized by metaphyseal dysostosis, unpigmented hair, and defective cellular immunity. We studied peripheral blood mononuclear cells (PBMC) of a boy with CHH and combined immunodeficiency in an attempt to characterize further the immune defect in this disease. Stimulation of his PBMC with mitogens was associated with severely depressed IL-2 and interferon-gamma (IFN-γ) synthesis and lL-2 receptor a-chain (IL-2Rα) expression and resulted in poor lymphocyte proliferation that was only modestly upregulated by the addition of recombinant IL-2 (rIL-2). The defective proliferation and lymphokine synthesis were not corrected by the addition of phorbol myristate acetate (PMA) and ionomycin, agents that bypass receptor-mediated signalling, indicative of a distal abnormality. Importantly, the levels of mRNA encoding c-myc, IL-2Rα, IL-2 and IFN-γ were markedly decreased in patient lymphocytes stimulated with PMA + ionomycin as compared to control lymphocytes The defect in the expression of these early activation genes was selective in that induction by mitogens of mRNA encoding other early activation gene products such as c- fos and c-jun was not impaired. These results suggest that the underlying defect in this patient and perhaps others with CHH may be an abnormality in a component of intracellular signalling pathways or in a trans-acting factor which regulates the expression of a selected number of early activation genes.
Origin of CD57+ T cells which increase at tumour sites in patients with colorectal cancer
Authors: Okada T , Hai T , Awach1 Y K , Moroda T , Takii Y , Hatakeyama K , Abo T 
Published: July 2010

SUMMARYHuman T cells carrying natural killer (NK) markers, CD57 or CD56 antigens, appear to be distinguishable from other T cell subsets in terms of their granular lymphocyte morphology and their numerical increase in patients with AIDS and in recipients of bone marrow transplantation. At the begining of this study, we observed that CD57+ T cells as well as CD56+ T cells were abundant at tumour sites in many patients with colorectal cancer. Since all these findings for CD57+ T cells are quite similar to those of extrathymic T cells seen in mice, we investigated how CD57+ T cells are distributed to various immune organs in humans. They were found to be present mainly in the bone marrow and liver, but to be completely absent in the thymus. Similar to the case of extrathymic T cells in mice, they were observed to consist of double-negative CD48+ subsets as well as single-positive subsets (preponderance of CD8+ cells), and to contain a considerable proportion of γδ T cells. These features are striking when compared with those of CD57+ T cells, which are characterized by an abundance of CD4+ subsets and αβ T cells. Not only at tumour sites but also in the peripheral blood, some patients with colorectal cancer displayed elevated levels of CD57+ cells. These results suggest that CD57+ T cells may be of extrathymic origin, possibly originating in the bone marrow and liver, and may be associated with tumour immunity, similar to another extrathymic population of CD56+ T cells in humans.
Localization of T cell receptor (TCR)- γδ+ T cells into human colorectal cancer: flow cytometric analysis of TCR-γδ expression in tumour-infiltrating lymphocytes
Authors: Watanabe N , Hizuta A , Tanaka N , Orita K 
Published: July 2010

SUMMARYWe analysed TCR-γδ expression in tumour-infiltrating lymphocytes (TIL) obtained from 13 patients with colorectal cancer and simultaneously isolated the T lymphocytes from normal intestinal tissue (IL) to compare the frequencies of TCR-γδ expression in TIL, IL. and peripheral blood lymphocytes (PBL) in the same patient. Flow cytometric analysis showed that the frequency of TCR-γδ expression in TIL (275 ± 1·84%) was significantly lower than that in IL (15·28 ± 9·45%, P &lt; 001). However, a larger quantity of TIL was separated than IL per unit weight of specimen, so the total number of γδ T cells obtained per unit weight was not different between tumour tissue and normal intestine. In addition, phenotypic analysis revealed that about half of the TCR-γδ TIL were CD8+ (CD4+, 3·0 ± 3·1%; CD8+, 54·7 ± 19·9%, mean ± s.d. of five patients), and a very similar result was obtained in TCR-γδ+ IL (CD4+ 2·7 ± 2·4%; CD8+, 53·1 ± 17·4%). In contrast, most TCR-γδ+ PBL were double-negative (CD4+. 3·2 ± 3·0%; CD8+ 20·6 ±7·4%). These results indicated that TCR-γδ+ CD8+ T cells selectively and consistently localized in colorectal tumour tissue, similarly to normal intestinal epithelium.
The effect on immunity of long-term intensive training in elite swimmers
Authors: Gleeson M , Mcdonald W A , Cripps A W , Pyne D B , Clancy R L , Fricker P A 
Published: July 2010

SUMMARY
The impact of long-term training on systemic and mucosal immunity was assessed prospectively in a cohort of elite swimmers over a 7-month training season in preparation for national championships. The results indicated significant suppression (P &lt; 0.05) of serum IgA. IgG and IgM and salivary IgA concentration in athletes associated with long-term training at an intensive level. There was also a trend towards lower IgG2 subclass levels in serum in athletes compared with controls (P= 0.07). There were no significant changes in numbers or percentages of B or T cell subsets, but there was a significant fall in natural killer (NK) cell numbers and percentages in athletes over the training season (P &lt; 0.05). After individual training sessions there was a significant decrease in salivary IgA levels for athletes compared with controls (P= 0.02). In athletes there was a downward trend in salivary IgA levels over the 7-month training period in both the pre-exercise (P= 0.06) and post-exercise samples (P= 0.04). There were no significant trends in salivary IgG levels over the study period in either athletes or controls. The only significant change in salivary IgM levels was an increase in detection rate in the pre-competition phase in athletes (P= 0.03). The study suggests that training of elite athletes at an intensive level over both short- and long-time frames suppresses both systemic and mucosal immunity. Protracted immune suppression linked with prolonged training may determine susceptibility to infection, particularly at times of major competitions.
T cells stimulatedin vitrohave a suppressive function but do not contain only regulatory T cells
Authors: Valencic E , Piscianz E , Tommasini A , Granzotto M 
Published: July 2010

SummaryThe generation of regulatory T cells (Tregs) in vitro represents an attractive possibility to set up cellular therapies that could prevent and cure autoimmune disorders. Different methods have been proposed to generate Tregs in vitro and to evaluate their phenotype and function. Moreover, the overlap between generation of activated and regulatory cells could often be underestimated. We showed that in vitro treatment of CD4+ CD25– lymphocytes with different stimuli leads to a good expression of CD25 and forkhead box P3 (FoxP3) on most cells, but to a full Treg phenotype (including CD127 negativity) in only a minor percentage of cells, ranging from 17·38% of cells treated with phytohaemagglutinin (PHA) to 50·91% of cells treated with T cell receptor (TCR) stimulation in association with transforming growth factor (TGF)-β. Some suppressive activity was demonstrated for T cells activated with all the different stimuli. However, while suppression mediated by TCR/TGF-β treated T cells was associated with an inhibition of both interleukin (IL)-2 and interferon (IFN)-γ in the co-culture supernatant, the suppression observed for PHA-activated cells occurred in the presence of large amounts of these cytokines. In conclusion, also taking into account other recent publications, caution should be taken in interpretation of data in the field of regulatory T cells.
A role for T cell-derived interleukin 22 in psoriatic skin inflammation
Authors: Boniface K , Guignouard E , Pedretti N , Garcia M , Delwail A , Bernard F-X , Nau F , Guillet G , Dagregorio G , Yssel H , Lecron J-C , Morel F 
Published: July 2010

Summary
Interleukin (IL)-22 is a T cell-derived cytokine that has been reported recently to induce cutaneous inflammation in an experimental murine model of psoriasis, and to induce in vitro an inflammatory-like phenotype. In the present study, we assessed the presence of IL-22 and the IL-22 receptor 1 (IL-22R1) in skin lesions, skin-derived T cells, as well as IL-22 levels in sera from patients with psoriasis. IL-22R1 and IL-10R2 transcripts are expressed at a similar level in psoriatic and healthy skin. In contrast, IL-22 mRNA expression was up-regulated in psoriatic skin lesions compared to normal skin, whereas IL-22 mRNA levels in peripheral blood mononuclear cells from psoriatic patients and normal subjects were similar. Circulating IL-22 levels were significantly higher in psoriatic patients than in normal subjects. T cells isolated from psoriatic skin produced higher levels of IL-22 in comparison to peripheral T cells isolated from the same patients. IL-10 was expressed at similar levels in skin biopsies and peripheral blood mononuclear cells of psoriatic patients and normal subjects. Finally, we show here that supernatants of lesional psoriatic skin-infiltrating T cells induce an inflammatory response by normal human epidermal keratinocytes, resembling that observed in psoriatic lesions. Taken together, the results reported in this study indicate that IL-22 is a cytokine produced by skin-infiltrating lymphocytes that is potentially involved in initiation and/or maintenance of the pathogenesis of psoriasis.
Increase of CD4+CD25+ regulatory T cells in the peripheral blood of patients with metastatic carcinoma: a Phase I clinical trial using cyclophosphamide and immunotherapy to eliminate CD4+CD25+ T lymphocytes
Authors: Audia S , Nicolas A , Cathelin D , Larmonier N , Ferrand C , Foucher P , Fanton A , Bergoin E , Maynadie M , Arnould L , Bateman A , Lorcerie B , Solary E , Chauffert B , Bonnotte B 
Published: July 2010

SummaryWe determined the number and functional status of CD4+CD25high regulatory T cells (Treg) in blood samples from patients with metastatic carcinoma, and evaluated their sensitivity to a single intravenous infusion of cyclophosphamide. Treg numbers were significantly higher in 49 patients with metastatic cancer (9·2% of CD4+ T cells) compared to 24 healthy donors (7·1%). These cells expressed the transcription factor forkhead box P3 (FoxP3), glucocorticoid-induced tumour necrosis factor receptor family-related protein (GITR) and intracellular CD152, and demonstrated a suppressive activity in vitro against CD4+CD25– autologous proliferation. At a single intravenous infusion, cyclophosphamide failed, in association with a non-specific immunotherapy by intratumoral bacille Calmette–Guérin (BCG), to modulate significantly Treg numbers or function. Metastatic cancer is associated with an expansion of peripheral blood CD4+CD25highFoxP3+GITR+CD152+Treg cells whose immunosuppressive properties do not differ from those of healthy subjects. Moreover, cyclophosphamide administration may not represent an optimal therapy to eliminate Treg, which further underlines the need to identify specific agents that would selectively deplete these cells.