bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue-dependent differences in the asynchronous appearance of mast cells in normal mice and in congenic mast cell-deficient mice after infusion of normal bone marrow cells
Authors: Du T , Friend D S , Austen K F , Katz H R 
Published: November 2003

SUMMARY
The time courses of the appearance of tissue mast cells in six sites were compared in normal WBB6F1-+/+ mice (+/+) and in congenic mast cell-deficient WBB6F1-W/Wv mice (W/Wv) that received an intravenous infusion of bone marrow cells from +/+mice (BM→W/Wv). As assessed by morphometric analysis of Carnoy’s solution-fixed, methylene blue-stained tissue sections, the density of mast cells in the stomach mucosa, stomach submucosa, and spleen of +/+ mice reached maximal levels by 8 weeks of age, whereas the density of mast cells in the skin, extraparenchymal airway walls, and lung parenchyma did not reach maximal levels until 18 weeks of age. When 8-week-old W/Wv mice were infused with 2×107 bone marrow cells from +/+ mice, mast cells appeared in the stomach mucosa and submucosa after 2.5 weeks, in the spleen and extraparenchymal airway walls after 5 weeks, and in the lung parenchyma after 10 weeks. Twenty weeks after bone marrow infusion, the mast cell densities in the spleen, stomach mucosa, and stomach submucosa were seven-, 13-, and five-fold greater, respectively, than those in age-matched +/+ mice, but were eight-, two-, and five-fold lower in the skin, extraparenchymal airway walls, and lung parenchyma, respectively. Thus, those tissues that in +/+ mice reached maximal mast cell densities earlier exhibited abnormally high mast cell densities in BM→W/Wv mice, and those that reached maximal mast cell densities later in +/+ mice had abnormally low mast cell densities in BM→W/Wv mice. Immunological and inflammatory responses are often compared in W/Wv and BM→W/Wv mice to assess mast cell dependency. Our results indicate that the capacity to restore a mast cell-dependent response in a particular tissue of the latter mice may relate to the local mast cell density and whether the immunological challenge activates mast cells only in that tissue or systematically with attendant widespread release of proinflammatory mediators.
Immune dysregulation to Ethiopian immigrants in Israel: relevance to helminth infections?
Authors: Bentwich Z , Weisman Z , Moroz C , Bar-Yehuda S , Kalinkovich A 
Published: November 2003

SUMMARY
The infectious disease background and particularly the helminth infections that are endemic in Africa could have profound effects on the host immune system. Studies that we have performed on an Ethiopian HIV− immigrant population that has recently reached Israel, lend support to this notion. They have indeed revealed a very high prevalence of helminth and several other infections with an extreme immune dysregulation, consisting of: (i) highly elevated plasma IgE, IgG, placental isoferritin, p75 soluble TNF receptor (sTNFR) levels and very high blood eosinophilia; (ii) increased secretion from phytohaemagglutinin (PHA)-simulated peripheral blood mononuclear cells (PBMC) of the cytokines IL-2, IL-4, IL-10 and p75s sTNFR, and decreased secretion of interferon-gamma (IFN-γ) and IL-6; (iii) increased and decreased surface expression of p75 TNFR and IL-6 receptor on lymphocytes, respectively. The causal relationship between this immune dysregulation and the infectious background is highly suggestive, and could have far-reaching implications in the resistance to other infections.
Phospholipids and reactive nitrogen intermediates collaborate in expression of the T cell mitogenesis-inhibitory activity of immunosuppressive macrophages induced in mycobacterial infection
Authors: Tomioka H , Kishimoto T , Maw W W 
Published: November 2003

SUMMARY
We studied the role of phospholipids and nitric oxide in expression of the suppressor activity of splenic macrophages induced by Mycobacterium avium-intracellulare complex infection (MAIC-induced macrophages) in mice against mitogenic response of concanavalin A (Con A)-stimulated splenocytes (SPC) as follows. First, phosphatidylserine (PS) and phosphatidylinositol were found to suppress Con A-induced mitogenesis of SPC via inhibition of IL-2 production and acquisition of IL-2 reactivity in Con A-stimulated T cells. The mitogenesis-inhibitory activity of PS was increased when SPC were cultured under mildly acidic condition (pH 6.3). When SPC were pretreated with PS for 24 h prior to Con A blastogenesis, their mitogenic response was irreversibly abrogated. Second, NG-monomethyl-l-arginine, an inhibitor of nitric oxide (NO) synthase, was found to attenuate in part the expression of the suppressor activity of MAIC-induced macrophages. Third, reactive nitrogen intermediates (RNI) including NO generated from acidified NO−2 exerted potent inhibitory activity against SPC mitogenic response, and the suppressive activity of RNI was significantly augmented by the combination with PS. These findings indicate that phospholipids and RNI play an important role in the expression of suppressor activity of MAIC-induced macrophages as the effector molecules.
Effect of rapamycin on the expression of the IL-2 receptor (CD25)
Authors: Woerly G , Brooks N , Ryffel B 
Published: November 2003

SUMMARY
The immunosuppressive macrolide rapamycin inhibits cytokine-driven proliferation of lymphocytes, acting at a later stage of T lymphocyte activation than the related compound FK506 or cyclosporin, which block IL-2 transcription. However, the effect of rapamycin on the expression of the IL-2 receptor α-chain (CD25) is less well documented. This study has investigated the effect of rapamycin on mRNA levels of CD25 and membrane expression of IL-2 receptor in human primary T lymphocytes activated by various stimuli. Rapamycin surprisingly inhibits CD25 upregulation subsequent to anti-CD3 or ionomycin stimulation. These effects are not secondary to an IL-2 mediated CD25 up-regulation, as rapamycin inhibits neither IL-2 synthesis nor IL-2-induced CD25 mRNA. Interestingly, sensitivity to rapamycin correlates with the requirement of de novo protein synthesis, as demonstrated by anisomycin inhibition of both ionomycin- and CD3-induced CD25 transcription. Thus, rapamycin inhibition of T cell activation may involve not only IL-2 driven proliferation, but also suppression of CD25 up-regulation.
Regulation and production of IL-8 by human proximal tubular epithelial cells in vitro
Authors: Gerritsma J S J , Hiemstra P S , Gerritsen A F , Prodjosudjadi W , Verweij C L , van Es L A , Daha M R 
Published: November 2003

SUMMARY
A number of inflammatory kidney diseases are associated with interstitial nephritis and influx of leucocytes in the renal interstitium. Potentially the influx of neutrophils in the interstitium may be induced by the chemotactic cytokine IL-8. In the present study we have analysed the production of IL-8 by cultured human proximal tubular epithelial cells (PTEC) in response to a number of proinflammatory cytokines. Primary cell lines of proximal tubular epithelium obtained from ten different kidneys, and cultured under serum-free conditions, were found to produce IL-8 to different degrees from not detectable levels up to 10.8±1.5 ng IL-8 per 1×105 cells in 72 h. Gel filtration chromatography of PTEC supernatant indicated that the size of IL-8 of PTEC is 15.1 and 8.1 kD, and is chemotactically active for polymorphonuclear neutrophils (PMN). Addition of 0.5 ng/ml rIL-1α or 1000 U/ml recombinant tumour necrosis factor-alpha (TNF-α) to the culture media of PTEC induced an up-regulation of IL-8 production up to 6.3-fold and 3.0-fold, respectively. The up-regulation by IL-1α and TNF-α was dose- and time-dependent. In contrast, 500 U/ml recombinant interferon-gamma (rIFN-γ) down-regulated the production of IL-8 3.4-fold. Northern blot analysis showed that IL-1α and TNF-α increased the expression of IL-8 mRNA, whereas IFN-γ reduced IL-8 mRNA expression. Taken together, these experiments indicate that human PTEC are a potential source of IL-8 in the kidney, and that IL-8 produced in the proximal tubule can be induced by various proinflammatory cytokines.
Glucocorticoids induced down-regulation of glucocorticoid receptor mRNA expression in asthma
Authors: Vachier I , Roux S , Chanez P , Loubatière J , Térouanne B , Nicolas J C , Godard P 
Published: November 2003

SUMMARY
Although their precise mechanism of action remains to be elucidated, glucocorticoids represent the most effective therapy in the treatment of asthma. Interactions between the glucocorticoid receptor and the AP-1 complex have been shown to regulate the transcription of some genes, including glucocorticoid receptor itself. The aim of the present study was to compare the expression of mRNA for glucocorticoid receptor in human blood monocytes obtained from seven unstable untreated asthmatic patients who were subsequently treated with high doses of parenteral corticosteroid (methyl prednisolone 120 mg/day) for 10 days. mRNA expression was identified after RNA extraction using RNAzol and analysed after reverse transcriptase, by polymerase chain reaction using a semiquantitative competitive hybridization assay. All asthmatic patients showed an improvement in their FEV1 values after corticosteroid treatment (per cent of predicted value 68.28±4.93 versus 95.57±6.41, P&lt;0.02), and a significant decrease for glucocorticoid receptor mRNA expression (P&lt;0.02) was observed in their monocytes. This is the first report of an ex vivo down-regulation for the glucocorticoid receptor mRNA expression, following corticosteroid treatment.
Administration of anti-CD3 monoclonal antibody during experimental Chagas’ disease induces CD8+ cell-dependent lethal shock
Authors: Jacobs F , Dubois C , Carlier Y , Goldman M 
Published: November 2003

SUMMARY
The injection of the 145-2C11 anti-CD3 MoAb in mice induces a polyclonal T cell activation resulting in the release of several cytokines, including interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α). As these cytokines are known to be involved in the host defence against Trypanosoma cruzi, we measured serum levels of IFN-γ and TNF-α after injection of the 145-2C11 MoAb in the course of experimental murine Chagas' disease. Compared with control mice, T. cruzi-infected BALB/c mice were found to be primed to secrete very high levels of IFN-γ and TNF-α from the second and the first week of infection, respectively, up to the chronic phase. In vivo cell depletion experiments indicated that CD8+ T cells were responsible for these dramatic hyperproductions of IFN-γ and TNF-α. While all control mice survived anti-CD3 MoAb injection, a high lethality rate was observed in T. cruzi-infected mice within 24 h after anti-CD3 MoAb challenge. Pretreatment with neutralizing anti-IFN-γ MoAb or depletion of CD8+ T cell population dramatically decreased the mortality induced by anti-CD3 MoAb in T. cruzi-infected mice. Finally, we showed that anti-CD3 MoAb injection in T. cruzi-infected mice was followed by a massive release of nitric oxide (NO) metabolites, which was partially reduced by IFN-γ or TNF-α neutralization. The administration of the NO synthase inhibitor n-nitro-l-arginine methyl ester (L-NAME) before anti-CD3 MoAb challenge did not prevent and even enhanced lethality in T. cruzi-infected mice, suggesting that NO overproduction and lethal shock are not causally related. We conclude that injection of anti-CD3 MoAb in the course of experimental Chagas’ disease induces a CD8+ cell-dependent shock mediated by IFN-γ and TNF-α.
The enigma of CD57+CD28– T cell expansion—anergy or activation?
Authors: Kern F , Ode-Hakim S , Vogt K , Höflich C , Reinke P , Volk H D 
Published: November 2003

SUMMARY
Expansion of a CD57+CD8+ T lymphocyte subset has been reported in HIV and human cytomegalovirus (HCMV) infection. Almost all of these T cells lack CD28 expression. While CD28– cells are often associated with anergy, some authors believe their expansion in HIV infection precipitates immunodeficiency. We studied 15 randomly chosen patients with immune activation and observed that CD57+CD28– T cell expansion may occur in various conditions and to the same degree as in HIV infection without resulting in immunodeficiency. Triple colour flow cytometry also revealed that the CD57 and CD28 antigens are coexpressed in only 3% of CD8+ T cells, irrespective of the underlying condition, so that almost all CD57+CD8+ cells are always CD28–. Analysis of Fas (CD95) expression with respect to CD28 expression on CD4+ and CD8+ T cells from 10 additional patients indicated no increased commitment to apoptosis in CD28– T cells. Semiquantitative polymerase chain reaction (PCR) comparing CD28+ and CD28–CD8+ T cells with respect to cytokine gene expression (tumour necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), IL-1β) in five renal transplant patients with expansion of the CD57+ subset detected no cytokine gene expression deficit in CD28– T cells. A direct association of increased proportions of CD57+CD28–CD8+ T cells with immunodeficiency/anergy is disputed.
The metabolism of C9 in normal subjects and in patients with autoimmune disease
Authors: Greenstein J D , Peake P W , Charlesworth J A 
Published: November 2003

SUMMARY
The metabolism of the ninth component of complement (C9) was studied in eight healthy subjects and nine patients with autoimmune disease, including seven with systemic lupus erythematosus (SLE) and one each with mesangial IgA nephropathy and mixed essential cryoglobulinaemia. In normal subjects the metabolic parameters (mean ± s.d.) were: fractional catabolic rate (FCR): 2.92 ± 0.36%/h, plasma half-life (T1/2): 42.5 ± 6.7 h, and extravascular/intravascular distribution ratio (EV/IV): 0.56 ± 0.12. In patients the FCR was 3.38 ± 0.70%/h, the T1/2 was 37.6 ± 10.2 h, and the EV/IV was 0.55 ± 0.19. Patients with reduced total serum haemolytic activity (i.e. CH50 &lt; 68% of normal human serum (NHS), n = 7) had significantly higher FCR (3.57 ± 0.67%/h) and shorter T1/2 (33.5 ± 6.8 h) than the control group (both P &lt; 0.05). The plasma concentration of the terminal complement complex (i.e. soluble TCC or SC5b-9) was higher in patients (median (range): 515 (300–1879 μg/l)) than in normal subjects (313 (229–402 μg/l); P &lt; 0.01) and showed a positive correlation with the FCR of C9 (r = 0.61, P &lt; 0.01). Plasma C9 production rate was also greater in patients (0.11 ± 0.05 mg/kg per h) compared with control subjects (0.07 ± 0.03 mg/kg per h, P &lt; 0.05), and was associated with a higher C9 concentration in patients’ sera (76 ± 13 mg/lversus 61 ± 14 mg/lP &lt; 0.05). These results demonstrate that C9 is rapidly metabolized in normal humans and that hypercatabolism occurs in patients with autoimmune disease and complement activation. This was despite the presence of normal or elevated serum C9 levels and normal compartmental distribution.
Distribution of human colonic dendritic cells and macrophages
Authors: Pavli P , Maxwell L , van de Pol E , Doe W F 
Published: November 2003

SUMMARY
To define the phenotype of intestinal dendritic cells and macrophages, resected colonic specimens were used to obtain lamina propria cell suspensions by EDTA treatment, then enzymatic digestion. The phenotype of dendritic cell-enriched suspensions was compared with that of macrophage-enriched populations by immunocytochemistry using the avidin-biotin-peroxidase (ABC) system and immunoelectron microscopy. Dendritic cells expressed HLA-DR (L243) and HLA-DQ-associated (RFD1) antigens and CD68 in a perinuclear distribution. Staining for S100 was weak or absent. Macrophages also expressed HLA markers (L243 and RFD1) and CD68. The 25F9 antigen was expressed strongly, whilst CD14 was absent from cells isolated from non-inflamed tissues. To determine their anatomic distribution, immunohistochemistry was performed using single- and double-labelling techniques (ABC ± alkaline phosphatase anti-alkaline phosphatase method). Mutually exclusive subsets of 25F9+ and S100+cells were seen: 25F9+ macrophages were concentrated in a band immediately beneath the luminal epithelium; S100+/HLA-DR+ dendritic cells formed a reticular network throughout the lamina propria and beneath the basement membrane of the crypts. This distribution suggests that macrophages may help regulate intestinal responses by acting as the first line of defence against the entry of luminal antigens. A breach of the macrophage ‘barrier’ by invading antigens may necessitate the recruitment of T cell responses by immunostimulatory dendritic cells.
Influence of the mouse Bcg
Tbc-1 and xid genes on resistance and immune responses to tuberculosis infection and efficacy of bacille Calmette–Guérin (BCG) vaccination
Authors: Nikonenko B V , Apt A S , Mezhlumova M B , Avdienko V G , Yeremeev V V , Moroz A M 
Published: November 2003

SUMMARY
We have studied the role of three mouse distinct non-H-2 genes (BcgTbc-1xid) in several phenomena of antituberculosis immunity and resistance. On the basis of median survival time (MST) of mice following infection with virulent Mycobacterium tuberculosis H37Rv, Bcg gene did not control resistance to the lethal dose of H37Rv infection in non-vaccinated and Myco. bovis (BCG)-vaccinated mice. However, Bcgr allele, in comparison with Bcgs allele, determined more effective suppression of an early multiplication in spleens of H37Rv mycobacteria after a low dose (5 × 104 colony-forming units (CFU)) injection. CBA/N mice, which are not protected efficiently against tuberculous challenge by BCG vaccination, were characterized by a decreased in vitro proliferation of immune lymph node cells, both spontaneous and stimulated with mycobacterial antigens. The decreased proliferation was due to immunosuppression caused by interactions between responding T cells and CBA/N antigen-presenting cells (APC). We have confirmed that the defective response to BCG-vaccination in CBA/N mice is linked with the X-chromosome and thus is presumably determined by the xid gene itself. I/St mice (Tbc-1s), supersusceptible to H37Rv infection, were not able to restrict the growth of H37Rv mycobacteria in spleens, even following infection with a low dose (5 × 104), but restricted the growth of Mycobovis BCG more effectively than Bcgs mice.
Identification of human IgG autoantibodies specific for IL-10
Authors: Menetrier-Caux C , Briere F , Jouvenne P , Peyron E , Peyron F , Banchereau J 
Published: November 2003

SUMMARY
Since autoantibodies to IL-1α, interferon-alpha (IFN-α) and IL-6 have been described, this study concentrated on the search for autoantibodies to hIL-10 using an assay based on the precipitation of 125I-hIL-10 anti-IL-10 autoantibody complexes using Protein G-Sepharose. Among 1860 tested sera, only seven were found to specifically precipitate IL-10, thus indicating the rare occurrence of such autoantibodies. Four of those seven anti-IL-10 autoantibody sera were specific for hIL-10, two recognized both human and viral IL-10, while the last one recognized human, viral and murine IL-10, thus suggesting the existence of at least three different epitopic specificities. The purification of anti-IL-10 autoantibody from one serum demonstrated the existence of a single (IgG1, λ) autoantibody that neutralized IL-10 biological activity. Thus, autoantibodies to IL-10 may represent natural antagonists to IL-10.
Effect of low dose UVB irradiation on the migratory properties and functional capacities of human skin dendritic cells
Authors: Richters C D , Reits E A J , van Pelt A M , Hoekstra M J , van Baare J , du Pont J S , Kamperdijk E W A 
Published: November 2003

SUMMARY
We recently described the ‘spontaneous’ migration of skin dendritic cells out of human split skin during culture. Since newly infiltrating cells from the circulation are excluded, this in vitro model is very suitable for studying the effect of UVB irradiation on the migratory properties, phenotype and functional capacities of skin cells. In the present study, we show that UVB irradiation of the skin before the culture period results in a significantly lower number of migrated cells that could be obtained compared with untreated skin. Relatively more dendritic cells of the population that migrated from UVB-irradiated skin were of dermal origin, as indicated by a higher percentage of CD1b+ cells. These data imply that UVB irradiation inhibits migration, especially of the epidermal Langerhans cells. Ultrastructural analysis of the irradiated skin revealed that the UVB dose used did not cause any directly visible damage to the cells. However, the cell population that had migrated from UVB-irradiated skin showed a significantly lower capacity to stimulate allogeneic T cells. This was not due to a lower expression of MHC class II on these cells. The percentage of cells expressing B7.1, B7.2 and LFA-3 was decreased in the population migrated from irradiated skin. The possible mechanism underlying the UVB-induced suppression is discussed.
Thyroid peroxidase autoantibody epitopic ‘fingerprints’ in juvenile Hashimoto’s thyroiditis: evidence for conservation over time and in families
Authors: Jaume J C , Burek C L , Hoffman W H , Rose N R , McLachlan S M , Rapoport B 
Published: November 2003

SUMMARY
In Hashimoto’s thyroiditis, the humoral component is manifest by autoantibodies to thyroid peroxidase (TPO). Epitopic ‘fingerprinting’ of polyclonal serum TPO autoantibodies has been facilitated by the molecular cloning and expression as Fab of a repertoire of human TPO autoantibody genes. To investigate whether TPO autoantibody fingerprints are (i) stable over long periods of time (∼15 years), and (ii) inherited, we studied a cohort of nine patients with juvenile Hashimoto’s thyroiditis and 21 first degree relatives of four of these patients. Fingerprints were determined by competition between four selected Fab and serum autoantibodies for binding to 125I-TPO. Regardless of titre, the TPO epitopic profile was stable in 10/12 individuals whose TPO autoantibody levels were sufficient for analysis on two or three occasions over 12–15 years. Although the TPO epitopic fingerprint profiles in two families raised the possibility of inheritance, overall the data from all four families did not reveal an obvious pattern of genetic control. In no family was the TPO epitopic fingerprint associated with HLA A, B or DR. In conclusion, TPO autoantibody epitopic fingerprints are frequently conserved over many years. Studies on additional families are necessary to establish whether or not the epitopic profiles of TPO autoantibodies are inherited.
Immunohistological study of the depressed cutaneous DTH response in sheep naturally infected with an ovine lentivirus (Maedi-Visna virus)
Authors: Pyrah I T G , Watt N J 
Published: November 2003

SUMMARY
The gross and immunohistological characteristics of the purified protein derivative (PPD)-induced cutaneous DTH reaction were studied in a group of sheep naturally infected with Maedi-Visna virus (MVV), and compared with reactions obtained in a matched control group. There was a marked, but variable, depression in the DTH lesion in the MVV group associated with a decreased density of polymorphonuclear neutrophils (PMN) and CD4+ cells in the early reaction. There were no significant differences in the densities of CD8+, γ/δ T cells, macrophages, B cells and MHC class II-expressing cells. This work indicates that there is a significant alteration in the initial trafficking of PMN and CD4+ cells into a DTH response area in sheep infected with MVV.