bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mature helper T cell requirement for immunoglobulin production by neonatal naive B cells injected intraperitoneally into severe combined immunodeficient (SCID) mice
Authors: HASUI M , MIYAWAKI T , ICHIHARA T , NIIDA Y , IWAI K , YACHIE A , SEKI H , TANIGUCHI N 
Published: July 2010

SUMMARYIt is accepted that human neonatal naive B cells produce mainly IgM in vivo as well as in vitro. Our previous work has demonstrated that i.p. injection of neonatal B cells together with adult mature T cells induces substantial levels of human IgG in the serum of SCID recipient mice. The present study was further attempted to determine the cellular components required for immunoglobulin production by neonatal B cells in SCID mice. When neonatal B and adult T cells were transferred into the SCID mice, human immunoglobulins, largely of IgG, were maximally detected in the serum around 6 weeks after a cell transfer. Depletion of CD4+ T cells from adult T cells resulted in undetectable levels of human immunoglobulin in the serum. By contrast, CD4+ T cell-enriched populations exhibited an enhancing effect on immunoglobulin production by neonatal B cells. Higher levels of immunoglobulin, including IgA and IgM, were detected in the peritoneal fluid than in the serum as early as 2 weeks after the cell transfer. Human T cells expressing activation antigens such as CD45RO and HLA-DR antigens were identified in the peritoneal lavages. These results suggest that neonatal naive B cells are able to differentiate into cells producing all classes of immunoglobulin in the presence of mature CD4+ T cells in a SCID mouse environment. The peritoneal cavity of SCID mice appears to provide a suitable place for immune responses by human cells, possibly in association with a certain xenogeneic reaction.
Expression of human T lymphotropic virus type 1 (HTLV-1) tax/rex gene in fresh bronchoalveolar lavage cells of HTLV-1-infected individuals
Authors: HIGASHIYAMA Y , KATAMINE S , KOHNO S , MUKAE H , HINO S , MIYAMOTO T , HARA K 
Published: July 2010

SUMMARY
Accumulating evidence has suggested the involvement of HTLV-1 in the inflammatory lesions of various organs, including the lung. However, the causal relationship between HTLV-1 and inflammatory responses in the organs remains to be elucidated. In order to evaluate the expression of HTLV-1 and its effects in the lung, we examined the expression of mRNA for the HTLV-1 tax/rex gene in fresh bronchoalveolar lavage cells (BALC) and peripheral blood mononuclear cells (PBMC) of 23 seropositive individuals, including six patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), by use of an improved method of reverse transcription-polymerase chain reaction (RT-PCR). The tax/rex mRNA was more frequently detected in BALC than in PBMC. All the HAM/TSP patients and eight of 17 carriers without neurological symptoms showed the expression of tax/rex mRNA in the BALC. IgM class antibodies to HTLV-1 were preferentially detected in sera of the tax/rex mRNA-positive individuals. The detection of tax/rex mRNA correlated closely with the presence of lymphocytosis accompanied by an elevated proportion of IL-2 receptor-bearing T cells in the BALC. Our findings indicate the crucial role of viral expression in the inflammatory response in the lung in HTLV-1-infected individuals.
Active immunization by a dengue virus-induced cytokine
Authors: CHATURVEDI U C , MUKERJEE R , DHAWAN R 
Published: July 2010

SUMMARY
Dengue type 2 virus (DV)-induced cytotoxic factor (CF) is capable of reproducing various pathological lesions in mice that are seen in human dengue. The present study was undertaken to investigate the protective effect of active immunization of mice with CF, Mice were immunized with 5 μg of CF and prevention of CF-induced increase in capillary permeability and damage to the blood brain barrier were studied at weekly intervals, up to 48 weeks, by challenging with 3 μg of CF, Maximum protection against increase in capillary permeability and damage to the blood-brain barrier was observed in week 4 after immunization. A breakthrough in the protection occurred with higher doses of CF in a dose-dependent manner. Challenge with a lethal intracerebral (i.e.) dose of DV showed significantly prolonged mean survival time and delayed onset of symptoms of sickness in the immunized mice compared with the normal mice, but the titre of the virus in the brain was similar in the two groups. On i.p. challenge with the virus the protection against damage to the blood-brain barrier was 86±7% at week 4 and 17±4% at week 26 after immunization. Sera obtained from the immunized mice showed the presence of CF-specific antibodies by ELISA, Western blot, and by neutralization of the cytotoxic activity of CF in vitro. The present study describes successful prevention of a cytokine-induced pathology by specific active immunization.
Circulating adhesion molecules in sarcoidosis
Authors: HAMBLIN A S , SHAKOOR Z , KAPAHI P , HASKARD D 
Published: July 2010

SUMMARYSarcoidosis is a disease of unknown etiology characterized by non-caseating granulomata together with a number of systemic abnormalities. We have recently shown these include increased expression of the integrins CD11/CD18 on peripheral blood leucocytes. Here we have measured serum levels of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1), E-selectin and vascular cell adhesion molecule-1 (VCAM-1) in 23 patients and 14 normal controls using antigen capture sandwich ELISAs. Median circulating E-selectin levels in the patients were nearly three times those of the controls (P&lt;0·0001, Mann-Whitney U-test), whilst ICAM-I but not VCAM-1 levels were only slightly elevated. These results show that endothelial cell activation and shedding of E-selectin into the circulation are additional features of the pathology of sarcoidosis.
Establishment of a monoclonal antibody to plasma cells: a comparison with CD38 and PCA-1
Authors: HATA H , MATSUZAKI H , MATSUNO F , SONOKI T , TAKEMOTO S , KURTBAYASHI N , NAGASAKI A , TAKATSUKI K 
Published: July 2010

SUMMARYA new monoclonal antibody which recognizes plasma cells was developed by utilizing two myeloma cell lines, KMS12PE (12PE) and KMS12BM (12BM). established from the pleural of fusion and bone marrow, respectively, of the same patient. Since I2BM expresses CD20, CD38, and PCA-I antigens, while 12PE has lost CD20. 12PE is considered to be phenotypically more mature than 12BM. The 12PE cells were used to immunize a BALB/c mouse and a MoAb was produced which was more reactive to 12PE than to 12BM. Thus, a clone, D2, was obtained. On Western blotting, D2 detected a single band of 54 kD under both reduced and non-reduced conditions. This antigen was not detected by Western blotting in peripheral blood lymphocytes that had been stimulated with pokeweed mitogen (PWM) for 7 days or in those not so stimulated. On flow cytometry, D2 detected a myeloma cell line, RPMI 8226. Another myeloma cell line, U266, was negative for D2 antigen. Staining various cell lines by D2 and other antiplasma cell antibodies, PCA-1 and CD38, showed that D2 is distinct from PCA-1 and CD38. The fresh myeloma cells of 14 myeloma patients were stained by D2 and for other plasma cell antigens. D2 strongly stained three samples obtained from patients with clinically aggressive myeloma, while CD38 stained all cases except one. PCA-1 was positive in nine samples and negative in five. PCA-1 expression was observed in plasma cells obtained from pleural effusion and peripheral blood, while PCA-1-negative cases were not found in such samples, suggesting that PCA-I expression was related to extramedullary invasion. The morphology of the myeloma cells, classified according to Greipp's criteria, showed that there was no correlation between plasma cell antigen expression and plasma cell morphology. Analysis of D2 antigen expression should provide more information about the heterogeneity of myeloma cells.
Polymorphism of tumour necrosis factor-alpha (TNF-α) at position −308 in relation to ankylosing spondylitis
Authors: VERJANS G M G M , BRINKMAN B M N , VAN DOORNIK C E M , KIJLSTRA A , VERWEIJ C L 
Published: July 2010

SUMMARY
In addition to HLA-B27, other genetic factors are thought to be involved in the pathogenesis of ankylosing spondylitis (AS). Because of the localization, in the proximity of the HLA-B locus, and the biological activities of TNF-α, we investigated the association between AS and a single base polymorphism located at position – 308 of the TNF-α gene. An allele-specific polymerase chain reaction was developed to monitor this polymorphism. The frequency of the TNF-α alleles was determined in 66 AS patients and 37 healthy controls. The TNF-α allele frequency was not significantly different between AS patients and controls.
The demonstration of an essential role for macrophages in thein vivogeneration of IgG2a antibodies
Authors: BREWER J M , RICHMOND J , ALEXANDER J 
Published: July 2010

SUMMARYBALB/c mice were depleted of macrophages by intravenous inoculation of dichloromethylene diphosphonate entrapped in liposomes 24 h before primary and 24 h before secondary sensitization intravenously with 100/μg bovine serum albumin (BSA) or ovalbumin (OVA). The effectiveness of macrophage depletion was confirmed by immunocytochemistry. Five days and 14 days after secondary challenge with BSA, plasma samples from these and control mice inoculated with empty liposomes were examined for the production of BSA-specific IgG1 and lgG2a antibodies. Macrophage depletion resulted in a significantly increased production of the Th2 lymphocyte-associated IgG1 isotype, while the production of specific IgG2a antibodies, produced under the influence of Th1 cells, was totally ablated. Similar results were obtained when OVA was used as the test antigen. Furthermore, analysis of interferon-gamma (IFN-γ) production after antigen or concanavalin A (Con A) restimulation in vitro indicated that macrophage depletion m vivo significantly reduced production of this Th1 cell-associated cytokine. These results provide strong in vivo and in vitro evidence for the macrophage being the antigen-presenting cell population responsible for Th1 cell activation.
Retroviruses and autoimmune rheumatic diseases
Authors: KALDEN J R , GAY S 
Published: July 2010

SUMMARYIn autoimmune rheumatic diseases, retroviruses have been repeatedly discussed as important etiologic factors. However, despite a considerable amount of indirect evidence that retroviruses might indeed be involved in triggering or perpetuating autoimmune rheumatic diseases, clear cut direct evidence is still missing. Studies on arthropathies associated with HIV-1 or HTLV-1 infection as well as new experimental animal models like the Tax transgene mice and new data from the MLRlpr mouse model might help to answer the questions how and by what mechanisms retroviral infection may lead to autoimmune rheumatic diseases. From data obtained in the MLR/lpr mouse it seems obvious that a potential link of retroviruses, apoptosis and autogenes to autoimmune diseases opens exciting new approaches to the study of rheumatic disease pathogenesis.
Mapping of B cell epitopes on steroid 17α-hydroxylase, an autoantigen in autoimmune polyglandular syndrome type I
Authors: PETERSON P , KROHN K J E 
Published: July 2010

SUMMARYEarlier studies have shown that 17α-hydroxylase (P450cl7), steroid 21-hydroxylase (P45Dc21) and side-chain cleavage enzyme (P450scc) are the main autoantigens recognized by sera from patients with Addison's disease associated with autoimmune polyglandular syndrome type I (APS I). In this study we tried to identify the autoantigenic epitopes on P450c17 and compared the identified sequences with corresponding regions in two other adrenal autoantigens, P450scc and P450c21. A series of F450c17 cDNA fragments was expressed in Escherichia coli and the recognition of the corresponding protein fragments by patient sera was tested by immunoblotting. Four distinct epitope regions (ER) were found: ER1 (amino acids 122–148), ER2 (280–304), ER3 (396–432) and ER4 (466–508). B cell epitope prediction analysis showed that the four identified ERs were all located in regions of high predicted antigenicity. Homology search revealed that ER3 and ER4 but not ER1 and ER2 were related to similar sequences on P450c21. No significant homologies with P450SCC in these regions were found. Although all three P450 cytochromes are genuine autoantigens this finding suggests that the autoantibody reaction against P450c17 and P450c21 can partly be a result of immunological cross-reactivity.
Membrane-bound complement regulatory activity is decreased on vaccinia virus-infected cells
Authors: BARANYI L , OKADA N , BARANJI K , TAKIZAWA H , OKADA H 
Published: July 2010

SUMMARYDecay accelerating factor (DAF), membrane cofactor protein (MCP), complement receptor 1 and mouse Crry are cell surface-bound complement regulatory proteins capable of inhibiting C3 convertase activity on cell membranes, and therefore provide a substantial protection from attack by homologous complement activated either by the classical or by the alternative pathway. Decrease in complement regulatory activity might lead to spontaneous complement deposition and subsequent cell injury. MoAb 512 can inhibit the complement regulatory activity of molecules on rat cells, resulting in deposition of homologous complement. The antigen recognized by 512 MoAb in rats is homologous to mouse Crry. Fifteen to 20 h after infection with vaccinia virus, in vitro cultured KDH-8 rat hepatoma cells show a strong decrease in expression of Crry-like antigen, and proved to be sensitive to complement deposition when 1:5 diluted normal rat serum was added to the culture medium as a source of complement. Addition of complement to the cultured KDH-8 cells infected with a very low dose of vaccinia virus (1 plaque-forming unit (PFU)/1000 cells) substantially reduced spreading of virus infection in the cell culture, while inactivation of complement by heat or zymozan treatment abrogated the protective effect.
Soluble cell adhesion molecules and von Willebrand factor in children with Kawasaki disease
Authors: NASH M C , SHAH V , DILLON M J 
Published: July 2010

SUMMARYFifty-nine children with acute Kawasaki disease (KD), a childhood vasculitis, were compared with 35 children with fever due to infection and 48 healthy children. Levels of soluble E-selectin (sE-selectin), soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1)in the healthy children were double those found in adults. All three soluble cell adhesion molecules and von Willebrand factor (vWF) were higher in the children with KD than in the healthy children, but only sE-selectin, a marker for activated endothelial cells, and sICAM-1 were higher than in the febrile children. The high levels of vWF in KD appear to reflect the prominent acute-phase reaction. This information can help us to understand further the complex interactions between cytokines. circulating inflammatory cells and the vascular endothelium, and may lead to new therapeutic avenues in KD and other inflammatory diseases and vasculitides.
Large granular lymphocyte expansions in patients with Felty's syndrome: analysis using anti-T cell receptor Vβ-specific monoclonal antibodies
Authors: BOWMAN S J , BHAVNANI M , GEDDES G C , CORRIGALL V , BOYLSTON A W , PANAYI G S , LANCHBURY J S 
Published: July 2010

SUMMARYFelty's syndrome (FS), the association of rheumatoid arthritis (RA) and idiopathic neutropenia, remains an unexplained phenomenon. HLA-DR4 is found in over 90% of cases. Patients with FS may have a T cell lymphocytosis of CD3+CD8+CD57+ large granular lymphocytes (LGL syndrome). In this study of 47 patients with FS, 19% had clear evidence for LGL expansions, while in total 42% had variable evidence for the LGL syndrome using currently available techniques. Of these T cell expansions, 76% were clonal, as demonstrated by Southern blotting and analysis with T cell receptor (TCR) β chain constant region probes. This technique may fail to detect clonal populations in some patients. Cytofluorographic analysis using antibodies specific for TCR β chains identified patients with clonal LGL expansions with results comparable to those obtained with Southern blotting. No evidence for shared Vβ usage among expansions from different patients was seen. The role of LGL in RA and FS is currently unclear, but this technique offers a practical and accessible means of identifying patients with LGL expansions, as a starting point for further investigation.
No evidence for an independent role of anti-heparan sulphate reactivity apart from anti-DNA in lupus nephritis
Authors: HYLKEMA M N , ZWET I V D , KRAMERS C , VAN BRUGGEN M C J , SWAAK A J G , BERDEN J H M , SMEENK R J T 
Published: July 2010

SUMMARYThe presence of anti-heparan sulphate (HS) reactivity in serum is closely related to the occurrence of nephritis in patients with systemic lupus erythematosus (SLE). Since patients with lupus nephritis in general also have high titres of anti-DNA antibodies, we wanted to clarify the relationship between anti-HS and anti-DNA reactivity in serum. Therefore, we studied longitudinally six patients with lupus nephritis who experienced 12 exacerbations of their disease, and five SLE patients without nephritis experiencing 10 periods of non-renal disease exacerbations. In addition, we tested single serum samples of another 24 patients obtained during a renal disease exacerbation and 22 sera of patients without nephritis. The sera of all patients were tested for anti-DNA (Farr assay) and anti-HS reactivity (ELISA). We confirmed that SLE patients during renal exacerbations have a significantly higher anti-HS reactivity than patients without nephritis (P &lt; 0·003). In addition, patients with nephritis also had higher titres of anti-DNA antibodies during renal exacerbations than during non-renal exacerbations (P &lt; 0·01). A correlation between anti-DNA and anti-HS reactivity was observed (r= 0·40, P &lt; 0·02), which in itself explains the correlation between nephritis and anti-HS reactivity. Comparing sera from nephritis and non-nephritis patients matched for anti-DNA titre, we found no difference in anti-HS reactivity, and therefore must conclude that the anti-HS reactivity is a direct reflection of anti-DNA reactivity.
Defects in antigen-driven lymphocyte responses in common variable immunodeficiency (CVID) are due to a reduction in the number of antigen-specific CD4+ T cells
Authors: FUNAUCHI M , FARRANT J , MORENO C , WEBSTER A D B 
Published: July 2010

SUMMARYT cells from patients with CVID have defects that may relate to the failure in vivo of B cell production of antibodies. Antigen-driven responses of T cells from CVID patients and normal subjects have been assessed by measuring DNA synthesis in vitro. Low density cells enriched for antigen-presenting dendritic cells were pulsed with purified protein derivative (PPD) and cultured with autologous T cells. Overall, T cells from CVID patients showed a significantly low mean response to PPD, although non-specific DNA synthesis induced in CVID T cells by IL-2 was within the normal range. However, mean PPD-specific T cell responses in CVID were not restored by IL-2 irrespective of the presence of monocytes. Depletion of CD8+ cells also failed to restore the mean PPD response of CVID CD4+ T cells. Limiting dilution analysis showed that in CVID there was a reduced frequency of antigen-specific cells within the T cell preparations. The mean frequency of the PPD-specific T cells in cultures from patients vaccinated with bacille Calmette-Guérin (BCG) was reduced to 1 in 109000 T cells compared with 1 in 18 600 T cells in BCG-vaccinated normal donors. These data show that the reduced PPD-specific response in CVID is due to a partial peripheral loss of antigen-specific cells.
Modulation of the IL-1 cytokine network in keratinocytes by intracellular IL-1α and IL-1 receptor antagonist
Authors: PHILLIPS W G , FELDMANN M , BREATHNACH S M , BRENNAN F M 
Published: July 2010

SUMMARYThe IL-1 cytokine network in epidermal cells was studied in vitro, using the spontaneously transformed HaCAT human keratinocyte line. Intracellular (ic) IL-1α and IL-1 receptor antagonist protein (IL-1Ra) following cell lysis were readily identified assayed using a capture ELISA; whereas in culture supernatants IL-1Ra was not detected, and IL-1α was present at only very low levels. Confluent cultures of HaCAT cells were shown to provide optimal conditions for the study, since confluence increased the icIL-1Ra: IL-1α ratio to a level as seen in vivo, which was independent of Ca2+ concentration in the culture medium. The IL-1Ra extracted from HaCAT cell lysates was functionally active, as demonstrated in the mouse thymocyte co-proliferation assay which could be blocked using a rabbit anti-IL-1Ra antibody. Transforming growth factor-beta (TGF-α) stimulated a dose-dependent increase in HaCAT cell 1L-1α without changing IL-1Ra concentration, with a resultant reduction in the iclL-1Ra: IL-1α ratio from 320:1 to 100:1. Similarly, TGF-α, interferon-gamma (IFN-γ), IL-6, and tumour necrosis factor-alpha (TNF-α) substantially increased HaCAT cell IL-1α, but had no effect on the IL-1Ra. with a concomitant reduction in the icIL-1Ra: IL-1α ratio. In contrast to their effects on monocytes, IL-4and IL-10 at biologically active levels had no effect on IL-1α, IL-1Ra or the icIL-1Ra: IL-1a ratio in confluent HaCAT cells. Hydrocortisone reduced IL-1α to below the limit of sensitivity of the ELISA, and induced a small increase in IL-1Ra of questionable biological significance. Thus, regulation of the IL-1 cytokine network in keratinocytes involves modulation of icIL 1α rather than of icIL-1Ra levels, and is markedly different from that noted in monocytes.
Chemokine expression in rheumatoid arthritis (RA): evidence of RANTES and macrophage inflammatory protein (MIP)-1β production by synovial T cells
Authors: Robinson E , Keystone E C , Schall T J , Gillett N , Fish E N 
Published: July 2010

SUMMARYEarlier studies from this laboratory provided evidence for restricted cytokine expression in the T cell population in RA tissues. Specifically, IL-2, IL-4, IL-6 and interferon-gamma (IFN-γ) gene expression levels wore low. The selective chemoattractant and activation effects of chemokines on leucocytes identify them as potentially ideal candidates in mediating selective inflammatory processes in RA. Accordingly, we undertook studies to examine constitutive chemokine gene expression in RA tissues. RANTES, monocyte chemotactic protein-1 (MCP-1) and MIP-1β gene expression was examined in both the T and non-T cell populations in RA peripheral blood (PB), synovial fluid (SF) and synovial tissues (ST). Our results identified elevated levels of both RANTES and MIP-1β gene expression in circulating RA PB and SF T cells. By contrast, MCP-1 expression was virtually absent in RA PB, yet elevated MCP-1 mRNA levels were detected primarily in the non-T cell populations of the SF and ST samples. Histological examination of affected rheumatoid joints revealed extensive RANTES and MIP-1β expression in sites of lymphocyte infiltration and cell proliferation, namely the synovial lining and sublining layers. Fractionation of RA ST patient samples revealed that RANTES expression was restricted to the T cells, whereas MIP-1β expression was detected in both T and non-T fractions. These data suggest that MCP-1, MIP-1β and RANTES may have a central role in the trafficking of reactive molecules involved in immunoregulation and in the inflammatory processes in RA.