bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precursor frequencies for DNA-specific B lymphocytes in patients with systemic lupus erythematosus (SLE)
Authors: SCHWAB J , LUKOWSKY A , VOLKK H-D , PETER H H , MELCHERS I 
Published: July 2010

SUMMARYPrecursor frequencies for anti-DNA-secreting B cells were estimated in six healthy donors and 18 SLE patients with active and inactive disease. Precursors for IgG anti-dsDNA-secreting B cells were exclusively detected in SLE patients (73% of active patients and one inactive patient, 0.01 – 0.99% of IgG-producing B cells). These frequencies were in the same order of magnitude as frequencies of precursors for IgG anti-tetanus toxoid, which were detectable in three healthy volunteers after booster vaccination (0.07–0.8% of IgG-producing B cells), but not before (&lt;001%). Precursors for IgG anti-ss-DNA secreting B cells were observed in 33% of healthy donors and in 78% of SLE patients (0.01 – 0.32% of IgG-producing B cells). Only patient-derived IgG anti-DNA clones cross-reacted with (33%) or were monoreactive to dsDNA (12%). Precursors for IgM anti-DNA-secreting B cells were observed in healthy donors and SLE patients in comparable frequencies and with similar reactivities with ssDNA and dsDNA. Segregation analyses and sorting experiments showed that &gt;94% of clones secreting IgG anti-DNA were derived from in vivo sIgG + B cells. slgM + B cells were induced to switch in vitro; however, only twice were cultures containing IgM and IgG anti-DNA antibodies observed under clonal conditions, In conclusion, our results indicate that precursor B cells for IgG anti-dsDNA in SLE patients are similarly selected and expanded as are precursor B cells specific for foreign antigens such as tetanus toxoid.
Monoclonal IgM from patients with peripheral demyelinating neuropathies cross-react with bacterial polypeptides
Authors: BROUET J-C , MARIETTE X , GENDRON M-C , DUBREUIL M-L 
Published: July 2010

SUMMARYHuman monoclonal IgM associated with a demyelinating peripheral neuropathy often feature a distinct antibody activity directed against a glucuronyl sulphate epitope shared by myelin-associated glycoprotein (MAG), nerve glycolipids and low molecular weight peripheral nerve polypeptides- Earlier studies showed that these IgM use a diverse repertoire of VH, and VL genes which exhibit somatic mutations, possibly indicative of an antigen-driven process. Here, we investigated whether such monoclonal IgM may react with environmental bacterial antigens. We found that six patients' sera and purified monoclonal IgM, as well as IgM from supernatants of three clonal anti-MAG-secreting cell lines reacted with unique 90 -100kD polypeptides from extracts of two out of 10 bacterial species. Purified MAG was able to inhibit this reactivity. These results indicate molecular mimicry as a possible mechanism of this immunomediated neuropathy and associated clonal lymphoid disease.
Growth and major histocompatibility antigen expression regulation by IL-4, interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α) on human renal cell carcinoma
Authors: HILLMAN G G , PURI R K , KUKURUGA M A , PONTES J E , HAAS G P 
Published: July 2010

SUMMARYWe have recently shown that human renal cell carcinoma (RCC) tumour lines express high-affinity IL-4 receptors. Binding of IL-4 to RCC cells induced a growth inhibition in the range of 20 68%. To enhance the growth inhibitory effect of IL-4. we have tested the effects of two additional cytokines capable of directly affecting tumour cell growth. IFN-γ caused a significant inhibition of RCC tumour cell growth (up to 70%) in a dose-dependent manner, whereas the effect of TNF-α was more limited (0 20% inhibition). The addition of IL-4 to IFN-γ on RCC cells sensitive to lL-4 induced a greater inhibition of cell growth than that seen with each cytokine alone. IL-4 and IFN-γ rendered RCC cells more responsive to the inhibitory effect mediated by TNF-α, The combination of TNF-Q with IL-4 and IFN-γ induced an optimal growth inhibition (up lo 90 98%) of RCC cells. In addition to a direct anti-proliferative effect, we have demonstrated that these cytokines can also enhance the expression of MHC antigens on the surface of RCC tumour cell lines which may render the cells more immunogenic, All RCC lines tested expressed class 1 antigens, but not class II antigens. IFN-γ induced class II expression and up-regulated the expression of class I antigens on RCC cells. Class II antigen expression was detectable following 48 h incubation, and greater after 72 h with IFN-7. lL-4 minimally affected class I expression, whereas TNF-(v up-regulated class I antigen expression. IL-4 or TNF-α did not induce class II expression. The combination of The three cytokines slightly augmented the up-regulation of class I and class II antigens observed with IFN-γ alone. These observations confirm the direct interaction of IL-4, IFN-γ and TNF-a with RCC tumour cells. both at the level of growth regulation and MHC antigen expression, and suggest a therapeutic potential of the combination of the three cytokines for renal ceil carcinoma.
Fine specificity of the murine immune response to SV40 large tumour antigen utilizing synthetic peptides that define selected epitopes
Authors: BRIGHT R K , SHEARER M H , KENNEDY R C 
Published: July 2010

SUMMARYBaculovirus-derived recombinant simian virus 40 large tumour antigen (SV40 T-ag) was used to immunize BALB/c, C57Bl/6 and CB6/F, mice and their anti-SV40 T-ag antibody responses were examined for the ability to bind synthetic peptides representing six predicted B cell epitopes on SV40 T-ag. In C57B1/6 mice, anti-SV40 T-ag antibodies failed to bind any of the six SV40 T-ag peptides. However, the antibody responses induced in both BALB/c and CB6/F| mice recognized synthetic peptides corresponding to two distinct epitopes (amino acids 690 708 and 660 679, respectively) associated with the carboxyl-terminal half of SV40 T-ag, In addition, murine MoAbs (BALB/c) generated to native SV40 T-ag, and previously characterized as recognizing the carboxyl-terminus of SV40 T-ag by deletion mutant analysis, also bound the synthetic peptide (residues 690–708) defining the carboxyl-terminus of SV40 T-ag. These data indicate that the antibody responses induced in BALB/c and CB6/r-| mice by immunization with baculovirus-derived recombinant SV40 T-ag are capable of recognizing sequential carboxyl-terminal epitopes on SV40 T-ag defined by peptides 690 708 and 660-679. respectively. No statistically significant differences in anti-SV40 T-ag antibody titres were observed between the three inbred mouse strains. These data suggested that the fine specificities of the anti-SV40 T-ag responses as assessed by synthetic peptide binding were different in the three inbred strains of mice examined. Finally, in vivo tumour challenge studies comparing recombinant SV40 T-ag with the two carboxyl-terminus peptide epitopes indicated that some tumour immunity was induced in BALB/c, but not CB6/F1 mice, by immunization with peptide 690 708 conjugated to a carrier protein. These studies suggest that the carboxyl-terminal region of SV40 T-ag represents A continuous sequential epitope involved in both the antibody response to SV40 T-ag and tumour immunity in BALB/c mice.
Effects of cyclosporine and rapamycin on immunoglobulin production by preactivated human B cells
Authors: KIM H-S , RASKOVA J , DEGIANNIS D , RASKA K 
Published: July 2010

SUMMARYIn order to assess the direct effects of cyclosporine A (CsA) and rapamycin on B cells, we utilized a two-segment culture system of highly purified B lymphocytes consisting of induction (activation) in the presence of the formalinized Staphylococcus aureus bacteria and IL-2. and differentiation, respectively, in the presence of various combinations of cytokines. Results show that rapamycin strongly inhibited production of both IgM and IgG measured at the end of the secondary culture supported by IL-2/IL-6, whereas CsA up-regulated the immunoglobulin production. The stimulatory effect of CsA was also observed when preactivated B cells were recultured in absence of any cytokines. These results show that rapamycin and CsA have dearly distinct effects on human B lymphocyte responses in vitro. Rapamycin is a more potent in vitro immunosuppressant of B lymphocytes than CsA. It is effective at significantly lower concentrations, and it does not stimulate either the proliferation or antibody production by preactivated B cells.
Histones interact with anionic phospholipids with high avidity; its relevance for the binding of histone–antihistone immune complexes
Authors: PEREIRA L F , MARCO F M , BOIMORTO R , CATURLA A , BUSTOS A , CONCHA E G D E L A , SUBIZA J L 
Published: July 2010

SUMMARYAntibodies recognizing anionic phospholipids have been described in systemic lupus erythematosus (SLE) and other autoimmune diseases. Recent studies have shown that some of these antibodies may recognize a cardiolipin-binding protein (apolipoprotein H) rather than phospholipids. A similar possibility is conceivable for other cardiolipin-binding proteins that are targets of autoantibodies. In this study we have addressed whether this might be the case for histones, a set of highly cationic and widely distributed proteins that react in a well known autoantibody system. Our results indicate that: (i) histones bind to anionic phospholipids (cardiolipin and phosphatidylserine) with high avidity, but not to zwitterionic phospholipids (phosphatidylcholine); (ii) monoclonal and polyclonal antihistone antibodies recognize histones bound to cardiolipin; (iii) the addition of histones to serum samples containing antihistone antibodies often enhances their anticardiolipin reactivity. In addition, we have found that antihistone-producing hybridomas derived from MKL-lpr mice may show anticardiolipin activity due to the presence of histones in the cell culture supernatants with the resultant formation of immune complexes. Taken together, the results suggest a potential role for histones in the anticardiolipin activity detected in sera containing antihistone antibodies. These histone-phospholipid interactions should be taken into account when evaluating the pathogenic effects of antihistone antibodies or other autoantibodies reacting with nuclear components (e.g. nucleosomes) containing histones.
The cytotoxic analysis of T cell receptor Vδ+ T cell lines derived from the synovial fluid of rheumatoid arthritis patients
Authors: OHTA M , SATO N 
Published: July 2010

SUMMARYWe established six human T cell lines derived from rheumatoid arthritis synovial fluid (RASF). Phenotypically, T cell receptor (TCR) αδ T cells occupied the majority of these lines and most of them expressed the TCR Vi5l molecule. In contrast, Vδ2+ T cells, the majority population of peripheral blood 76 T cells, were rarely detected in these lines. To study the immunobiological roles of RASF Vδ1+ T ceils in RA development, their cytotoxic profile was studied. The results showed that these T cells selectively lysed Daudi, but not K562 cells. The cytotoxic response was MHC-unrestricted, and was inhibited by anti-CD3 MoAb. Moreover, the cold target inhibition assay showed that the cytotoxicity was competitively inhibited by autologous and allogeneic primarily cultured RA synovial cells as well as synovial sarconui and chondrosarcoma lines. However, PBL did not inhibit this cytotoxicity- These data suggest that Vδ1+ T cells in RASF may recognize the antigen which is commonly expressed on the surface of Daudi and the cells derived from RA synovium. We can assume that the cytotoxic Vδ1+ T cells are selectively expanded in RASF, playing a significant role for the pathogenesis of certain RA cases.
Analysis of the uveitogenic determinant in repeat structure of retinal interphotoreceptor retinoid-binding protein (IRBP)
Authors: INOUE H , TAKEUCHI M , TANAKA T , USUI M , ANDO S , TAGUCHI O 
Published: July 2010

SUMMARYIRBP is a glycolipoprotein with a four-fold partially homologous repeat structure approximately 300 residues in length, and is one of the retinal antigens capable of inducing experimental autoimmune uveoretinitis (EAU) in susceptible animals by their active immunization. The most immunopathogenic peptide of bovine IRBP for FAU in Lewis rats is reported to be the sequence 1169–1191 (PTARSVGAADGSSWEGVGVVPDV) with two immunogenic motifs common to T cell epitopes (underlined). The uveitogenic site of peptide 1169–1191 was localized at the carboxyl terminus (peptide 1182 1191) and not al the amino acid terminus (peptide 1169–1182). Repeat peptides of sequenee 11 79–1191 containing the four homologous residues (1182W. 1186G. 1187V and 1189P). that is the peptides 271–283, 579 591 and 880892. all elicited EAU. Peptide 579–591 could not stimulate proliferation of lymphocytes from rats immunized with IRBP, but had the capacity to adoptively transfer EAU. The roie of the homologous residues was examined using analogues of the uveitogenic peptide 1182–1194. in which each homologous residue was substituted by giycine (G) or leucine (L) (1182W→G, 1186G→L, 1187V→G, and 1189 P→G). One analogue (1186G →L) strongly diminished the ability to induce FAU. while the other three analogues completely abolished the ability, indicating that these homologous residues were essential for the induction of FAU. In addition, the uveitogenic peptides tested in this study were found not to contain the major epitope for antibody production.
Evaluation of serum levels of soluble CD4, CD8 and β2-microglobulin in visceral human leishmaniasis
Authors: VITALE G , MOCCIARO C , MALTA R , GAMBINO G , SPINELLI A , GIORDANO C , STASSI G , ARCOLEO F , MILANO S , CILLARI E 
Published: July 2010

SUMMARYThe levels of soluble CD4 (sCD4), sCD8 and β2-microglobulin (β2-M) were measured in sera from patients with visceral leishmaniasis during the course of infection. Levels of sCD4. sCD8 and β2-M were raised significantly above levels In normal sera and returned to the normal range after recovery. The decrease in the levels of CDS was related to a reduction of anaemia, leukopenia and thrombocytopenia. In contrast, sCD4 levels fluctuated during the period of infection. β2-M returned within normal range more rapidly than sCD8 secretion. Our results suggest that T cells are activated during infection, and that it is also possible that the raised levels of these soluble molecules play a role in the impairment of protective immunity.
Bacillus Calmette-Guérin (BCG) and immunoglobulins synergistically enhance mineral dust-induced production of reactive oxygen metabolites by human monocytes
Authors: NYBERG P , KLOCKARS M 
Published: July 2010

SUMMARY
The modulating effect of BCG and polyelonal immunoglobulin on mineral dust-induced production of reactive oxygen metabolites (ROM) by human monocytes was studied using luminoldependent chemiluminescence. BCG and immunoglobulin synergistically amplified the ROM production induced by chrysotile asbestos and quartz particles, and BCG caused a sharper dose response for poly-immunoglobulin added to the mineral dusts. Immunoglobulins did not affect zymosan yeast-induced ROM production, which was enhanced strongly by BCG. As there is evidence that phagocyte-derived ROM are of importance in mineral dust-induced lung injury, we suggest that the observed synergism between host response inflammatory mediators (polyimmunoglobulin) and exogenic Irritants (BCG) may contribute to the outcome of exposure of mineral dusts, and thus in part explain the individual variations in susceptibility to mineral dustinduced diseases.
Early impairment of gut mucosal immunity in HIV-1-infected children
Authors: QUESNEL A , MOJA P H , BLANCHE S , GRISCELLI C , GENIN C 
Published: July 2010

SUMMARYThis study was performed in 27 HIV-1+ children to characterize the IgA hyperglobulinaemia observed in the serum during the course of HIV-1 infection. By contrast with serum IgG, which increased very early, IgA elevation was related to the decrease of CD4+ cell percentage. It was demonstrated that IgA1 subclass increased selectively. Secretory IgA (SIgA) and IgA and IgG activity to gliadin, bovine serum albumin (BSA) and at a lower level to casein could be detected in the serum at the early stages of HIV infection, but SIgA levels and IgA activity to gliadin further increased during the course of immunodeficiency. By contrast, IgA and IgG activity to tetanus toxoid did not change. These data demonstrate that the hyper IgA, closely related to the degree of immunodeficiency, could be due in part to a disturbance of the gut mucosal immune system. Moreover, impaired intestinal immunity seems to appear very early, and to progress during the course of paediatric HIV-1 infection.
T cell differentiation and generation of the antigen-specific T cell repertoire in man: observations in MHC class II deficiency
Authors: MANNHALTER J W , WOLF H M , HAUBER I , MIRICKA M , GADNER H , EIBL M M 
Published: July 2010

SUMMARYThe circulating T cell pool of an MHC class II-deficient patient was shown to lack the MHC class II-specific T cell functions. This was demonstrated by the absence of MHC class Il-specific alloreactive T cells and a substantially decreased number of circulating CD4+ lymphocytes. The patient's T cells did respond to an allostimulus, although the restriction pattern of this reaction remains speculative. The function and distribution of peripheral T cell subsets from the patient resemble findings in MHC class II-deficient mice, which also lack interaction of T cell precursors with MHC class Il-bearing accessory cells during thymic differentiation. Our data support the concept that Tcell differentiation in humans is similar, and that the human MHC-restricted Tcell repertoire depends on prior interaction of T cell precursors with self MHC.
Restricted junctional diversity of T cell receptor δ gene rearrangements expressed in systemic lupus erythematosus (SLE) patients
Authors: OLIVE C , GATENBY P A , SERJEANTSON S W 
Published: July 2010

SUMMARYSLE is an autoimmune connective tissue disorder affecting multiple organs, in which T cells may play a central role. This study investigated T cell receptor (TCR) γ/δ repertoire expression in peripheral blood mononuclear cells (PBMC) of SLE patients and healthy individuals using variable (V) gene family-specific polymerase chain reaction (PCR) amplification of TCR cDNA. The expressed Vγ repertoires were diverse in SLE and control PBMC, although VγIV gene rearrangements were barely detectable or not expressed in some patients. In contrast, δ chain expression was limited in all SLE patients, with Vδ transcripts rearranged primarily to the Vδ1 and Vδ2 genes, as opposed to control PBMC, in which all six Vδ genes were detected. To assess the clonality of TCR populations. cDNA clones containing rearranged Vδ1, Vδ2 and Vγ9 transcripts were sequenced from PBMC of both patients and controls. For controls, δ chain junctional region sequences showed extensive molecular heterogeneity, since virtually all 34 Vδ1 and 32 Vδ2 cDNA clones analysed were unique. A few Vδ9 cDNA clones (3/21) had the same junctional region sequence motif (EVQEL) encoded largely by the Vγ9 and joining (J) γP gene segments. Identical Vγ9 junctional sequences were found in SLE patients that did not contain the EVQEL motif present in normal peripheral blood γ/δ lymphocytes. Moreover, the predominant Vδ1-Jδ-consiant (C) δ and Vδ2-Jδ-Cδ gene rearrangements expressed in SLE PBMC showed restricted junctional diversity, but the oligoclonal δ transcripts were different in each patient. These findings suggest in vivo oligoclonal expansion of γ/δ T cells in the periphery of SLE patients in response to a limited number of nominal ligands. Whether γ/δ T cells contribute to the development of systemic autoimmunity remains to be investigated.
Soluble CD8 and CD25 in serum of patients after heart transplantation
Authors: WIJNGAARD P L J , VAN DER MEULEN A , MEYLING F H J GMELIG , DE JONGE N , SCHUURMAN HENK-JAN 
Published: July 2010

SUMMARYTo evaluate the diagnostic value of serum cytokine levels and cytokine receptor levels in the diagnosis of acute rejection after heart transplantation, we measured soluble CD8 and soluble CD25 in the serum of heart transplant recipients. The results were compared with endomyocardial biopsy (EMB) histopathology, lymphocyte activation by morphologic inspection of peripheral blood cells (cytoimmunologic monitoring), clinically manifested infections, and the maintenance immunosuppressive therapy. Significantly increased levels were observed in eases of lymphocyte activation in cytoimmunologic monitoring indicative of either rejection or infection. In clinically documented cytomegalovirus (CMV), bacterial, and Pneumocystis carinii infections, increased levels of soluble CD25 were observed. Soluble CD8 was only increased in a single ease of P. carinii infection. A statistically significant correlation was calculated between the levels of soluble CDS and whole blood cyetosporin A level. Considering chemotherapy, the levels of soluble CD8 showed an inverse correlation with the daily dosage of azathioprine. In conclusion, the levels of soluble CD8 and CD25 are associated with lymphocyte activation in peripheral blood, but do not differentiate between lymphocyte activation indicative of rejection or infection. No relationship was observed between levels of soluble CD8 and CD25, and EMB histopathology. Therefore, the assessment of these two cell products has no diagnostic potential for monitoring acute rejection after heart transplantation.
Expression of p75 chain of IL-2 receptor in the early immunological reconstitution after allogeneic bone marrow transplantation
Authors: COMOLI P , MACCARIO R , MONTAGNA D , LABIRIO M , ZECCA M , CLEMENTI R , BONETTI F , LOCATELLI F 
Published: July 2010

SUMMARYExpression of p55 and p75 chains of IL-2 receptor (IL-2R) on the surface of both T and natural killer (NK) circulating lymphocytes was investigated in 14 paediatric patients given allogeneic bone marrow transplantation (BMT) from HLA-identical sibling or partially matched family donors. IL-2-induced proliferative and cytotoxic responses were also studied and all analysis was performed within 45 days from transplant. We found that, early after transplant, the percentage of p55+ and of p75+ peripheral blood lymphocytes (PBL) was not significantly different in patients who had received HLA-identical BMT (p55+ 8·04 ± 4·87%; p75+ 28·27 ± 18·85%) compared with healthy controls (p55+ 7·26 ± 6·17%; p75+19·42 ± 10·49%), while recipients of T cell-depleted marrow included a remarkably high percentage (76–90%) of p75+ PBL, which were mostly CD3− and co-expressed CD56 molecule. Comparable values of p55+ lymphocytes were observed in all patients and controls. However, in contrast to the other two groups, in recipients of T cell-depleted BMT the majority of these cells co-expressed p75 chain and CD56 antigen. rL-2-induced proliferation and lymphokine-activated killer (LAK) activity were detectable in all patients, and their values did not correlate with expression of p55 or p75 chains. Our data suggest that expansion of NK subsets expressing IL-2R chains after T cell-depleted BMT may be related to early reconstitution of natural immunity in the presence of allogeneic stimuli.