bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine responses to the native and recombinant forms of the major surface glycoprotein of Pneumocystis carinii
Authors: THEUS S A , SMULIAN A G , SULLIVAN D W , WALZER P D 
Published: November 2003

SUMMARY
Pneumocystis carinii is a major opportunistic pathogen and leading cause of morbidity in patients with AIDS. The major surface glycoprotein (MSG) of P. carinii, represented by a family of related proteins encoded by unique genes, is highly immunogenic and contains T cell-protective epitopes. We undertook the present study to define the CD4 T helper (Th) response by cytokine secretion to native MSG and a recombinant form of the protein, MSG-B. Spleen cells were collected from Lewis rats and restimulated with both native MSG and MSG-B. Within 24 h, the CD4 cells secreted high levels of interferon-gamma (IFN-γ) in response to both types of antigen, indicative of a Th1 response; however, after 72 h of incubation, only the native MSG stimulated secretion of IL-4 (Th2 response) from the cells. We then investigated whether the presence of IL-4 could alter the predominant Th1 phenotype by the CD4 cells in response to MSG and MSG-B. Cells cultured with native MSG and IL-4 produced low levels of IFN-γ and elevated levels of IL-4. Interestingly, cells incubated with MSG-B and IL-4 reduced production of IFN-γ, but were not stimulated to produce increased levels of IL-4. The presence of anti-IFN-γ antibody in the MSG- or MSG-B-stimulated cultures did not effect the expression of IFN-γ mRNA, suggesting that the generation of Th1 cells in response to MSG or MSG-B was not dependent on IFN-γ. We conclude that native MSG, which contains multiple forms of this antigen, and recombinant MSG elicit different cytokine responses in vitro. These data are not only important to studies of MSG, but may also be relevant to the role of MSG in the immunopathogenesis of P.carinii infection in vivo.
Human peritoneal B-1 cells and the influence of continuous ambulatory peritoneal dialysis on peritoneal and peripheral blood mononuclear cell (PBMC) composition and immunoglobulin levels
Authors: DONZE H H , LUE C , JULIAN B A , KUTTEH W H , KANTELE A , MESTECKY J 
Published: November 2003

SUMMARY
In mice, peritoneal B cells are composed of a unique B-1 cell population which can repopulate the intestinal lamina propria with IgA-producing cells, as well as contribute to the majority of serum IgM. In this study, peritoneal lymphocytes from patients starting continuous ambulatory peritoneal dialysis (CAPD) and from women undergoing bilateral tubal ligation (BTL) were analysed for the presence of a B-1 cell population as well as the expression of potential homing receptors. Up to 63% of the peritoneal B cells express surface antigen CD5, and most peritoneal lymphocytes express the mucosal homing receptors, α4β7 and αEβ7. When analysing serial samples collected from patients from the beginning of dialysis to 1 year, no marked changes were observed in serum or salivary immunoglobulin levels, although the peritoneal lymphocyte population was reduced by 50%. These data suggest that the phenotype of human peritoneal B-1 cells is similar to that of mice, but the contributions to the immune system may differ.
Oral tolerance in a murine model of relapsing experimental autoimmune uveoretinitis (EAU): induction of protective tolerance in primed animals
Authors: THURAU S R , CHAN C-C , NUSSENBLATT R B , CASPI R R 
Published: November 2003

SUMMARY
Oral administration of uveitogenic retinal antigens suppresses the expression of EAU induced by a subsequent immunization with these antigens. Effectiveness and mechanisms of oral tolerance in EAU have mainly been studied in the acute, monophasic model in Lewis rats by feeding antigen prior to induction of disease. In this study we investigated the effect of oral tolerance induction in the acute as well as the chronic-relapsing models in the B10.A mouse. In acute murine EAU we could effectively suppress disease by induction of oral tolerance prior to immunization. In the chronic-relapsing EAU, antigen feeding was started only after the animals had recovered from their first attack of uveitis. Under these experimental conditions the subsequent relapse was largely prevented. These experiments demonstrate that oral tolerance may have practical clinical implications in uveitis, which is predominantly a chronic-relapsing condition in humans.
Antibodies to β2-glycoprotein I—a specific marker for the antiphospholipid syndrome
Authors: GUERIN J , FEIGHERY C , SIM R B , JACKSON J 
Published: November 2003

SUMMARY
The antiphospholipid syndrome is a disorder characterized by recurrent thrombosis and the presence of antibodies specific to phospholipids. However, the diagnosis of this syndrome is hampered by the lack of a specific laboratory test. In this study an ELISA for the measurement of antibodies to solid-phase β2-glycoprotein I (β2-GPI) was established and compared with anticardiolipin antibodies for diagnosis of antiphospholipid syndrome. Significantly elevated levels of antibodies to β2-GPI were found in all patients with definite antiphospholipid syndrome (median  =  91 AU). Marginally elevated levels of antibodies to β2-GPI were observed in 5% of patients with systemic lupus erythematosus (SLE; median  =  4 AU), 1% with stroke (median  =  3 AU), 13% with infectious mononucleosis (median  =  3 AU), 10% with HIV infection (median  =  3 AU) and 8% with VDRL false-positive serology for syphilis (median  =  4 AU), but not in patients with rheumatoid factor, syphilis or carotid artery stenosis. In contrast, significantly raised levels of anticardiolipin antibodies were observed in 100% of patients with definite antiphospholipid syndrome, 30% with SLE, 88% with HIV infection, 94% with syphilis, 62% with infectious mononucleosis, 9% with rheumatoid factor-positive sera, 74% VDRL false-positive serology for syphilis, 47% with stroke and 0% with carotid artery stenosis. This solid-phase assay for antibodies to β2-GPI is highly specific for the antiphospholipid syndrome and represents an advance in the laboratory diagnosis of this disorder.
Regulation of cytokine gene expression by adjuvants in vivo
Authors: VICTORATOS P , YIANGOU M , AVRAMIDIS N , HADJIPETROU L 
Published: November 2003

SUMMARY
Antibody isotype affects biological activity of the antibodies and therefore should be considered in prevention of disease by vaccination. In previous reports, we demonstrated that adjuvants affect the antibody isotype switching process and favour the production of certain isotypes. The present study extends these findings and shows fundamental differences in the cytokine induction pattern according to the adjuvant used. Cytokine mRNA levels were determined by in situ RNA–RNA hybridization performed on splenocytes isolated from mice injected with different adjuvants. The results revealed that Freund's complete adjuvant (FCA), Freund's incomplete adjuvant (FIA), Al(OH)3 and QuilA administration results in a type-2 (humoral) response, increasing IL-4, IL-5 and IL-13 gene expression, while poly I:C exhibits a type-1 (cell-mediated) response, increasing the production of interferon-gamma (IFN-γ), IL-2 and IL-6 mRNA. Finally, BeSO4 and poly A:U augment IL-5 and IL-6 mRNA production, while lipopolysaccharide (LPS) and LiCl augment IL-6 and tumour necrosis factor-alpha (TNF-α) mRNA production. Also, the adjuvants appear capable of overcoming the inherent IL-2/IFN-γ and IL-4 dichotomy of C57Bl/6 and BALB/c mice, respectively, in response to cellular antigens such as Leishmania and herpessimplex virus (HSV). The overall data suggest that adjuvants direct the isotype switching process via induction of certain cytokines, a finding that can be useful in selection of the most efficient isotype of protective antibodies for disease prevention by vaccination.
IL-13 over-expression in skin is not confined to IgE-mediated skin inflammation
Authors: VAN DER PLOEG I , JEDDI TEHRANI M , MATUSEVICIENE G , WAHLGREN C F , FRANSSON J , SCHEYNIUS A 
Published: November 2003

SUMMARY
IL-13 is produced by T cells and, like IL-4, it can induce the production of IgE and IgG4. In order to investigate if IL-13 is a specific marker for atopic dermatitis (AD), IL-13 gene expression was analysed in chronic lichenified lesions and non-lesional skin of patients with AD, in involved and non-involved skin of patients with psoriasis, in positive tuberculin reactions in non-atopics, and in the skin of healthy control subjects. Patients with AD (n = 9) showed sensitization to common air-borne allergens (positive Phadiatop) and had total serum IgE values in the range from 10 to 4800 kU/l (median 170 kU/l ). Competitive reverse transcription-polymerase chain reaction (RT-PCR) was used to assess IL-13 gene expression in skin biopsy specimens. IL-13 gene expression was markedly higher in chronic lichenified lesions of patients with AD (P &lt; 0.01), and in the positive tuberculin reactions (P &lt; 0.01; n = 12) than in skin from healthy control subjects (n = 10). However, there was no significant difference in IL-13 gene expression in the skin of patients with psoriasis (n = 10) and that of healthy control subjects. The dermal cell infiltrates were larger and the relative amount of CD3+ and CD4+ cells in these infiltrates was higher in the skin of subjects with a positive tuberculin reaction than in lichenified AD skin. However, these differences were not reflected in differences in IL-13 gene expression. Different triggers of IL-13 gene expression may influence the diverse patterns of inflammation seen in different inflammatory skin disorders.
The production of IL-8 in cerebrospinal fluid in aseptic meningitis of children
Authors: ISHIGURO A , SUZUKI Y , INABA Y , FUKUSHIMA K , KOMIYAMA A , KOEFFLER H P , SHIMBO T 
Published: November 2003

SUMMARY
Neutrophils accumulate initially in the cerebrospinal fluid (CSF) of aseptic meningitis, perhaps because of increased levels of granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein-1α (MIP-1α), and IL-8 in the subarachnoid space. We studied levels of these cytokines in children with aseptic meningitis using ELISA. When meningeal symptoms existed, IL-8 levels (1399 ± 1600 ng/l, n = 32) in the CSF were significantly higher than those either after meningeal symptoms disappeared (61 ± 56 ng/l, n = 18) or in controls (44 ± 63 ng/l, n = 27) ( P &lt; 0.0001). High levels of IL-8 on admission dropped sequentially. Significant correlations were found between IL-8 levels and either neutrophil counts (r = 0.612), G-CSF levels (r = 0.873) or MIP-1α levels (r = 0.623) in the CSF of the affected patients (P &lt; 0.0001). IL-8 values in serum were lower than in the corresponding CSF samples from all individuals with meningeal symptoms. The IL-8 mRNA was detectable by reverse-transcribed polymerase chain reaction (PCR)-assisted amplification in fresh leucocytes from the CSF, but not from the peripheral blood of a healthy volunteer. The culture of CSF mononuclear cells produced high levels of IL-8 (∼ 2750 ng/l). These data indicate that IL-8 levels rise transiently at the initial stage of aseptic meningitis, and that mononuclear cells that migrate into the CSF are a cellular source of this chemokine. We suppose that IL-8, in addition to G-CSF and MIP-1α, contribute to the localized neutrophil accumulation during the disease.
CD28 costimulation and T lymphocyte proliferative responses in HIV-1 infection
Authors: CARLESIMO M , PONTESILLI O , VARANI A R , BERNARDI M L , MAZZONE A M , ROSSO R , GUERRA E C , CASSONE A , PAGANELLI R , AIUTI F 
Published: November 2003

SUMMARY
To investigate whether defective costimulatory signals could be involved in the loss of T lymphocyte functions during HIV-1 infection, we tested the effect of CD28 costimulation on both T cell receptor/CD3 and HIV-1 antigen-induced proliferative responses. Although CD3-mediated responses significantly decreased with more advanced stages of HIV-1 infection, the ability of potentiating the responses through CD28 costimulation was maintained at all stages and did not differ from that of HIV-1− subjects. When CD28 costimulation was studied in lymphocyte cultures stimulated with HIV-1 gp160 or p24, potentiation was seen only when a significant response was present without additional CD28 triggering, namely in subjects receiving active immunization with recombinant gp160. These results confirm the integrity of the CD28 pathway of costimulation during HIV-1 infection, and suggest that lymphocytes responding to soluble HIV-1 antigen are not deleted in HIV-1-infected patients, but do not receive significant priming during the natural course of the infection.
Induction of human IgE synthesis in B cells by a basophilic cell line, KU812
Authors: YANAGIHARA Y , KAJIWARA K , BASAKI Y , IKIZAWA K , AKIYAMA K , SAITO H 
Published: November 2003

SUMMARY
Induction of human IgE synthesis in B cells requires, in addition to IL-4 or IL-13, a second signal provided by CD40 ligand (CD40L) on activated Th2-type CD4+ T cells that do not or weakly express Fas ligand (FasL). Mast cells and basophils also produce IL-4 or IL-13 and express CD40L after immunologic or pharmacologic stimulation, although it is unknown whether these cells express FasL. This study investigated the capacity of KU812 cells, a human basophilic cell line, to produce IL-4 and IL-13, to express CD40L and FasL, and to induce IgE and IgG4 synthesis in human normal B cells. Upon stimulation of KU812 cells with either phorbol myristate acetate (PMA) or ionomycin (Iono), IL-4, but not IL-13, was produced in response to Iono, while IL-13, but not IL-4, was inducible by PMA. Moreover, both the time courses of IL-4 and IL-13 production and their amounts secreted were different; IL-4 production was transient, IL-13 production gradually increased, and IL-13 was heavily secreted as compared with IL-4. The combination of PMA and Iono (PMA/Iono) induced higher production of IL-4 or IL-13 than did Iono or PMA alone. KU812 cell-derived IL-4 and IL-13 had the ability to cause CD23 expression on B cells. PMA/Iono also up-regulated CD40L expression and induced a very low level expression of FasL. KU812 cells that had been activated by PMA/Iono followed by fixation could induce IgE and IgG4 synthesis in B cells in the presence of recombinant IL-4 or IL-13. This contact-dependent induction of IgE was completely abrogated by adding anti-CD40L MoAb or soluble CD40, whereas anti-FasL antibody did not significantly affect IgE production. These results indicate that activated KU812 cells produce biologically active IL-4 and IL-13, express functional CD40L, and exhibit weak induction of FasL, thereby supporting sufficient IgE production by B cells.
Differences in the rate of donor leucocyte migration between natural and drug-assisted tolerance following rat liver transplantation
Authors: LORD R , GOTO S , VARI F , EDWARDS-SMITH C , CHIBA S , SUNAGAWA M , LYNCH S V 
Published: November 2003

SUMMARY
The number involved in and the rate of migration of donor leucocytes into the following recipient organs (spleen, thymus, bone marrow, lung and mesenteric lymph nodes) were measured in two rat models of orthotopic liver transplantation (OLT) using donor-specific MHC class I antibodies. The first OLT model is one that does not require immunosuppression in order to achieve tolerance and involved the transplantation of DA (MHC haplotype, RT1a) livers into PVG (RT1c) recipients. The second model was one that required a 7-day (10 mg/kg) treatment with cyclosporin A (CsA) to achieve tolerance and used DA donors into Lewis (RT11) recipients. Recipient organs were biopsied on days 3, 20 and 87 following OLT and donor leucocyte migration was quantified by immunohistochemistry and computer densitometry of immunoblots of detergent-solublized tissues in order to resolve both membrane-bound and soluble donor MHC class I antigen. In a separate experiment, spleen biopsies were taken following OLT on days 3 and 15 from the naturally tolerizing OLT model (DA into PVG), treated with and without CsA for 7 days and compared with the (DA into Lewis) model. The initial rate of leucocyte migration between days 3 and 21 following OLT was found to be the most rapid into the spleen, followed by the bone marrow and mesenteric lymph nodes in the naturally tolerant (DA into PVG) model when compared with the (DA into Lewis) model. The number of donor leucocytes in the spleen and mesenteric lymph nodes in both models was, however, approximately the same by 87 days. No real difference in the rate of leucocyte migration was seen in the thymus or the lung for both transplant models over the time course assayed. CsA was found to lower the rate of donor leucocyte migration only over the period it was administered. The rate of donor leucocyte migration into the spleen was still much lower 15 days after OLT in the (DA into Lewis) model compared with the (DA into PVG) model treated with and without CsA. Thus the differences in the rate of donor leucocyte migration into the spleen, bone marrow and mesenteric lymph nodes immediately following OLT may offer an explanation as to why the (DA into PVG) combination is able to accept a transplanted liver without immunosuppressive therapy.
High serum level of soluble CD30 in acute primary HIV-1 infection
Authors: PIZZOLO G , VINANTE F , NADALI G , KRAMPERA M , MOROSATO L , CHILOSI M , RAITERI R , SINICCO A 
Published: November 2003

SUMMARY
CD30 has been suggested to play a role in HIV infection. In this study the serum concentration of soluble CD30 (sCD30) was determined by an ELISA essay on samples collected from patients with acute primary HIV-1 infection during the acute phase (n = 17) and after seroconversion (n = 13). sCD30 during acute infection was consistently elevated (137·58 ± 120·33 versus 6·4 ± 5·4 U/ml (mean ± s.d.) in normal controls; P &lt; 0·0001) and decreased after seroconversion (49·1 ± 66·17 U/ml; P = 0·0018 compared with acute infection). This trend mirrored the disappearance of detectable levels of HIV antigen in the blood, resulting in a direct correlation between sCD30 and HIVAg values (P = 0·002). These data suggest that the high levels of sCD30 observed during the peak concentration of HIVAg in acute primary HIV infection might reflect the high rate of viral replication.
T helper responsiveness in human Loa loa infection; defective specific proliferation and cytokine production by CD4+ T cells from microfilaraemic subjects compared with amicrofilaraemics
Authors: BAIZE S , WAHL G , SOBOSLAY P T , EGWANG T G , GEORGES A J 
Published: November 2003

SUMMARY
The proliferation and cytokine profiles of peripheral blood mononuclear cells (PBMC) from microfilaraemic (Mf+) subjects infected by Loa loa in response to antigens of several parasitic stages were compared with those from amicrofilaraemic (Mf−) individuals. While a strong lymphoproliferative response and consistent levels of both Th1 (IL-2, interferon-gamma (IFN-γ)) and Th2 (IL-4, IL-5) type cytokines were observed in response to adult worm (AW) and microfilariae (Mf) antigen in Mf− individuals, Mf+ subjects were characterized by a T cell unresponsiveness, including proliferation, cytokine production and IL-2 mRNA expression. Conversely, T cell responsiveness to mitogens and non-specific antigen were similar in the two endemic populations. Depletion of lymphocyte subpopulations indicated that T CD4+ were mainly involved in the specific cellular response. In contrast to other cytokines, IL-10 was produced in response to all parasitic stages, in both Mf+ and Mf− patients. Neutralization of IL-10 did not restore cytokine production in Mf+ patients, while B7 mRNA expression was similar between Mf+ and Mf− subjects in response to Mf antigen, suggesting that IL-10 was not the only factor responsible for T cell unresponsiveness. Mf+ patients have lower Mf antigen-specific IgG levels compared with Mf−, and there is a significant correlation between Mf antigen-specific antibodies and IL-5 responses. These findings suggest that Mf− status is correlated with T helper responsiveness, including proliferation and production of both Th1- and Th2-type cytokines, whereas Mf+ status is characterized by unresponsiveness of the same cell population, induced and/or maintained by microfilariae.
Oxidized low-density lipoprotein (Ox-LDL) but not LDL aggravates the manifestations of experimental antiphospholipid syndrome (APS)
Authors: GEORGE J , BLANK M , HOJNIK M , BAR-MEIR E , KOIKE T , MATSUURA E , LORBER M , AVIRAM M , SHOENFELD Y 
Published: November 2003

SUMMARY
Ox-LDL is thought to play a major role in atherogenesis. The mechanisms mediating the deleterious influences of Ox-LDL include foam cell formation and cell cytotoxicity. The production of anti-Ox-LDL antibodies results in the formation of immune complexes which are taken up at enhanced rate by macrophages, leading to foam cell formation. APS is characterized by repeated venous and arterial thromboembolic phenomena, recurrent fetal loss and thrombocytopenia, associated with the presence of antibodies to negatively charged phospholipids (aPL) (i.e. cardiolipin, phosphatidylserine). Phospholipids bear structural resemblance to LDL, and several studies have indeed proved that aPL display cross-reactivity with anti-Ox-LDL antibodies. In this study we assessed the capacity of oxidized and native forms of LDL to aggravate the clinical picture of experimentally induced APS in naive mice. Mice were actively immunized intradermally with anticardiolipin antibodies and developed a clinical picture resembling APS in humans. Subsequently, the mice were infused with either Ox-LDL, native LDL or PBS, and similar regimens were applied to controls. APS mice infused with Ox-LDL were found to exhibit a significantly more severe form of the disease in comparison with native LDL- and PBS-infused mice, expressed by lower platelet counts (261 000/mm3, 535 000/mm3 and 455 000/mm3, respectively), longer activated partial thromboplastin time (aPTT) (99 ± 12 s, 63 ± 8 s and 74 ± 8 s, respectively) and higher fetal resorption rates (72·7%, 34·4% and 32·6%, respectively). The results of this study show that Ox-LDL, compared with native LDL, aggravates the clinical manifestations of experimental APS and suggest that cross-reactivity of Ox-LDL with phospholipids may provide a pathogenic explanation for this effect.
Calcium channel blockers suppress the contact hypersensitivity reaction (CHR) by inhibiting antigen transport and presentation by epidermal Langerhans cells in mice
Authors: KATOH N , HIRANO S , KISHIMOTO S , YASUNO H 
Published: November 2003

SUMMARY
Since Langerhans cells (LC) are the principal antigen-presenting cells among epidermal cells, treatments suppressing LC function may inhibit CHR. Although calcium channel blockers (CCB) have been shown to suppress the functions of several immunologically active cells, little is known about their effect on LC. In this study we show that pretreatment with topical 1% nifedipine or verapamil HCl significantly suppressed both the sensitization and elicitation phases of a CHR in mice. We then investigated whether CCB affected LC. Flow cytometric analysis of regional lymph node cells obtained 24 h after applying FITC demonstrated that topical CCB treatment significantly reduced the percentage of FITC+ NLDC-145+ cells, suggesting that CCB had suppressed antigen transport by LC. In vitro treatment with nifedipine or verapamil significantly suppressed the antigen-presenting capacity of LC in a dose-dependent manner. In addition, in vitro CCB treatment reduced the percentage of class II MHC antigen-positive epidermal cells and significantly suppressed class II MHC and B7-1 levels in LC, as determined by flow cytometry and reverse transcriptase-polymerase chain reaction, whereas surface expression of B7-2 and mRNA was only weakly reduced. Neither expression of CD45 nor the percentage of CD45+ cells were affected, suggesting that the effects of CCB on LC were not due to cytotoxicity. Our results suggest that CCB inhibit CHR, at least in part, by suppressing the functions of LC.