bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allelic Variation in the TNF‐β Gene Does Not Explain the Low TNF‐β Response in Patients With Primary Biliary Cirrhosis
Authors: MESSER G. , SPENGLER U. , JUNG M. C. , HONOLD G. , EISENBURG J. , SCHOLZ S. , ALBBRT E. D. , PAPE G. R. , RIETHMÜLLER G. , WEISS E. H. 
Published: June 2006

Autoimmune disorders in humans are often associated with particular alleles of major histocompatibility genes. However, the chronic inflammatory liver disease primary biliary cirrhosis (PBC) has not been found to be correlated with certain haplotypes so far.Interestingly, an impaired production of tumour necrosis factor β (TNF‐β) upon mitogen stimulation was observed for PBC patients, especially in the immunologically active stages of the disease. Furthermore, the identification of alleles of the TNF‐β gene which differ in one unique amino acid, and in the production of TNF‐β after phytohaemagglutinin stimulation, has prompted the idea of a possible linkage between the impaired TNF‐β response in PBC and the genetic prevalence of a certain TNF haplotype.We report here a rapid method for typing the TNFB*1 and TNFB*2 genes by a standard polymerase chain reaction, PBC patients(n = 60)as well as randumized healthy controls (n = 179) of the Munich area were studied for the occurrence of the TNF alleles. No deviation was found in the PBC collective (0.7) for the TNFB*2 distribution when compared with the control (0.67).
B Lymphocyte Fibronectin Receptors: Expression and Utilization
Authors: STUPACK D. G. , STEWART S. , CARTER W. G. , WAYNER E. A. , WILKINS J. A. 
Published: June 2006

Lymphocytes adhere to fibronectin (FN) via multiple receptors of the VLA β1 CD29 integrin) family. The cellular requirement for the variety of FN receptors (FNR) which have been described is unclear, but they may be associated with differential signalling processes, cooperative effects which may stabilize cellular attachment, or cell homing and retention processes. The present study was undertaken to examine the FN adherence properties and receptor utilization patterns of human B cells. Often B‐cell culture lines which were studied, six demonstrated a significant adherence to FN. Among these. Tour employed α4β1. (CD49d/29) and two employed α4β1/α5β1 (CD49d/29, CD49e/29), There was no apparent correlation between the differentiation status of the lilies and their FNR utilization patterns. Furthermore, expression of FNR alone was not sufficient to confer FN binding potential.Freshly isolated tonsil B cells did not display significant adherence to FN, Following stimulation, a marked increase in VLA antigens was observed, and the capacity to attach to FN‐coated surfaces was co‐acquired. Analysis of the induced bulk B‐cell population demonstrated that both α4β1 and aα5β1 were used for adherence. These results clearly indicate that activated B cells, similar to T cells, may express and utilize α5β1 as a FNR.
Immune Responses to 6 and 30‐kDa Mycobacterial Antigens in Rheumatoid Patients, and Vβ Usage by Specific Synovial T‐Cell Lines and Fresh T Cells
Authors: SIOUD M. , KJELDSEN‐KRAGH J. , QUAYLE A. J , WTKER H. G , SØRSKAAR D. , NATVIG J. B. , FØRRE Ø. 
Published: June 2006

We have investigated both the humoral and the cellular immune responses of patients with juvenile rheumatoid arthritis (JRA) and rheumatoid arthritis (RA) to mycobacterial antigens. The JRA group was not Bacillus Calmette Guerin (BCG) vaccinated whilst the majority of the RA group was.As determined by immunoblotting, 79% of sera from patients with JRA reacted mainly with a 18.6‐kDa protein (P18,6), whilst 70% of sera from patients with RA reacted mainly with a 30‐kDa protein (P30) of BCG, M. tuberculosis and M, kansasii. In contrast, only a moderate proportion of the control sera (25% of adult and 20% of children) showed reactivity to P30, and none of the samples had significant reactivity with the P18,6 antigen. Furthermore, T‐cell proliferation to the P18,6 and P30 antigens was detected in the majority of JRA and RA patients, and was nearly always higher in synovial fluid (SF) than in the peripheral blood (PB).We also investigated the usage of Vvβ family genes in P18,6, and P30 antigen‐specific T‐cell lines established from the SF of one patient with active RA, We showed that Vβ‐2‐4,‐5,‐6,‐7,‐14,‐17,‐18 and Vβ19 were over‐represented compared with other known Vβ families. We also noted that the proportion of Vβ14 was higher in freshly isolated SF mononuclear cells compared with the blood in this patient and in 2 out of 4 other RA patients examined. Other Vβ families such as Vβ6. Vβ8 Vβ16 Vβ18 and Vβ19 were also over‐represented in the SF compared with the blood in some patients. Taken together our results provide more information concerning the role of mycobacterial antigens in RA and suggest that there may be an in vivo clonal expansion of T lymphocytes in the synovium.
Interleukin 4 and Interferon Gamma Production in Restimulated CD4+ and CD8+ Cells Indicates Memory Type Responsiveness
Authors: SANDER B. , CARDELL S. , MÖLLER E. 
Published: June 2006

Interleukin 4 (IL‐4) and interferon gamma (IFN‐γ) production was analysed in murine spleen cells during primary and secondary mitogen Stimulation in vitro. The kinetics, frequency and phenotype of single lymphokine‐producing cells were studied by combining intracytoplasmatic immunofluorescence and surface staining. Both IL‐4 and IFN‐γ was produced by CD4+ as well as CD8+ cells, however 75–80% of IL‐4 producers were CD4+ and 90% or IFN‐γ+ cells were CD8+In primary stimulations. concanavalin. A (Con A) activation or anti‐CD3 antibody together with phorbol 12‐myristale 13‐aeetate (PMA) induced different patterns of lymphokine production. Approximately the same frequency of IFN‐γ+ cells was induced by both stimulation procedures but the kinetics was different with a peak at 30 h using Con A and at 52 h using anti‐CD2and PMA. IL‐4 production peaked al 52 h, but the frequency of IL‐4+ cells was 8–10 times higher after stimulation by anii‐CD3 and PMA than after Con A stimulation.During restimulation of the mitogen activated cells, lymphokines were rapidly produced; both IL‐4and IFN‐γ production peaked at 8–11 h. Only a small increase in the frequency of IL‐4+ cells was seen, at most two to three limes. No evidence for a major shift of lymphokine produced between primary and secondary stimulations could be found. Instead, the pattern of lymphokine production induced by the primary stimulus was dominant also in secondary cultures irrespective of stimulation condition.
Idiotypic Profile of Natural Autoantibodies in Newborn and Young Adult BALB/c Mice
Authors: ZÖLLER M. , ACHTNICH M. 
Published: June 2006

Idiotypic profiles of autoreactive monoclonal antibodies (MoAb) were evaluated by their reactivity with a panel of alkaline phosphatase (AP)‐coupled detector MoAb derived from the same fusions. Attention was given to the question of whether differences exist between MoAb derived from spleen cells (SC) or thymocytes (TC) and whether ID profiles would change during post‐natal development.In the newborn, natural auioantibodies and MoAb which did not react with any one of eight autoantigens displayed different ID profiles, autoreactive MoAb being characterized by the expression of a restricted pattern of ID. During post‐natal development. changes of ID expression were only observed with autoreactive MoAb. Many ID which were detected on MoAb derived from 6‐day‐old mice were not detected on SC‐derived MoAb from young adults, while a few ID were significantly over‐represented. Furthermore, especially with TC‐derived MoAb, a clear linkage between certain idiotypes and autoantigen spectficities could be demonstrated.Thus, in contract to non‐autoreactivc MoAb, natural autoantibodies in the young adult were characterised by expressing only a selected number of ID al high frequency. Furthermore, the B‐cell enivironment apparently played a role, since there were marked differences between ID profiles of TC‐ versus SC‐derived MoAb. The data are interpreted in the sense that expansion and maturation of naturally activated autoreactive B cells are controlled rather than being random processes.
Autoreactive Antibodies in Thymus and Spleen of Neonatal and Young Adult BALB/c Mice: Influence of Prenatal Tolerization
Authors: ACHTNICH M. , ZÖLLER M. 
Published: June 2006

The repertoire of autoantibody‐producing B cells was evaluated in a collection of spleen‐ and thymus‐derived hybridomas from 6‐ and 2S‐day‐old BALB/c mice, which were untreated or prenatally tolerized with trinitrobenzenesulphonic acid (TNBS). MoAb were tested for their reactivity with TNP‐BSA and the autoantigens thyroglaobulin (TG), myoglobin (MG), actin (AC), cytochrome C (CY), collagen (CO), transferrin (TF), single‐stranded DNA (dsDNA), double‐stranded DNA (dsDNA), and bromelain‐lreated mouse red blood cells (BrMRBC).More than 10% of spleen cell (SC)‐derived MoA b from 6‐and 28‐day‐old control mice did bind to AC, ssDNA, dsDNA, MY, and TG, the frequency of MoA b reacting with MY, TG, And BrMRBC increasing with age. Thymus cell (TC)‐derived hybridomas contained autoreactive clones Eoo. but only few of them produced multireactive MoAb.MoAb from prenatally TNBS‐treated mice were more frequently autoreactive than MoAb from control mice, especially if derived from TC hybridomas. The most remarkable difference in the reactivity pattern as compared with MoAb from untreated mice consisted of a significant increase in the frequency of TG‐, My‐, ssDNA‐ and above all of dsDNA‐reactive MoAb, all TC‐derived multireactive MoAb binding to dsDNA.The differences in autoreactivily between MoAb from prenatally untreated and TNBS‐treated mice as well as age‐ and organ‐related variations support the interpretation that part of the repertoire of naturally activated B cells is not random but is influenced by and responding to the available panel of self antigens.
Increased Frequencies of the CD29 and CD57 Markers and Decreased Frequency of CD45RA Within CD4+ and CD8+ Subsets after Allogeneic Bone Marrow Transplantation in Man
Authors: MøLLER J. , DICKMEISS E. , RYDER L. P. , JACOBSEN N. , SVEJGAARD A. 
Published: June 2006

Two monoclonal antibodies, anti‐CD45RA and anti‐CD29, reciprocally divide the CD4+ and CD8+ lymphocytes into CD4+ CD45RA+, CD4+ CD29+, CD8+ CD45RA+ and CD8+ CD29+ subsets. The CD4+ CD45RA+, CD4+ CD29+ and CD8+ CD45RA+ possess suppressor‐inducer, helper‐inducer and suppressor‐effector functions respectively. Since the role of these subsets has not been established after allogeneic bone marrow transplantation we studied lymphocyte subpopulations in 12 patients 45‐ 227 days after the procedure.The fraction of CD4+ lymphocytes was significantly (P= 0.0005) decreased to 20±9% versus 43±3% in controls. Within the CD4+ compartment, we found an increase in the fraction of CD4+ cells that co‐expressed CD29 (CD29+/CD4+) to 92±10% versus 48±15% (P=0.008) in controls and a concommittant decrease m CD45RA+/CD4+ to 16±12% versus 56±25% (P=0.008)Patients were also noted to have an increase in the percentage of CD8+ lymphocytes to 41±5% compared to 23±4% in controls (P=0.0004), Examination of the CD8+ subsets revealed a significant increase in the CD29+/CD8+ fraction to 97±3% versus 64±2% in controls (P= 0.008) and a decrease in the CD45RA+/CD8+ fraction to 36±11% versus 70±21% (P= 0.008).The number of cells co‐expressing CD57 were also determined within the CD4+ and CD8+ subsets. In patients CD57+/CD4+ were increased to 29±7% versus 1±1% in controls (P=0.04), and CD57+/CD8+ to 49±12% versus 23±9% (P=0.02).Since CD29+ and CD57+ cells have a poor capability for IL‐2 production and proliferation this shift in subset distribution may account for some of the defects in cellular immunity seen within the first year after allogeneic bone marrow transplantation.
C5 Does Not Play a Major Role in the Immune Response of Mice to SRBC In Vivo
Authors: VAN DEN BERG C. W. , VAN HORSSEN P. J. , HOFHUIS K. M. A. , AERTS P. C. , VAN DIJK H. 
Published: June 2006

The role of complement component C 5 in the immune response of mice to sheep red blood cells (SRBC) was investigated, Congenic C5‐suffcieal and C 5‐deficient B10.D2 mice Lind genetically CS‐deficient DBA/2 mice. as such or supplemented with C5‐suficient serum, were used as experimental animals. C5‐substitution of the C5‐deficient mice resulted m measurable CS levels for days. The functional half‐life of C? in C5‐deficienl DBA 2 mice was about 21 h.No significant differences between the IgM‐responses of C5bearing and naive C5‐delicient animals were observed. This suggests t ha C5 does not play a major role in the primary humoral immune response of mice in vivo, although C5 seems to do so in in vitro experiments, even with the same antigen. Antigen‐induced C5‐production by C5‐defieient mice as one of the explanations of the in vitro, in vivo discrepancy could not be confirmed experimentally.
IgG Subclasses in Bronchoalveolar Lavage Fluid from Patients with Asthma
Authors: OUT T. A. , VAN DE GRAAF E. A. , VAN DEN BERG N. J. , JANSEN H. M. 
Published: June 2006

We have measured Immunoglobulin G (IgG) subclasses in serum and bronchoalveolar lavage fluid (BALF) from 12 non‐smoking patients with stable asthma and 9 non‐smoking healthy volunteers to obtain information on their possible role in local immunological reactions. The quotients (concentration of IgG subclass in BALF)/(concentration of IgG subclass in serum) were calculated. In controls QIgG3 were lower than QIgGI, QIgG2 and QlgG4.The IgG subclasses in BALF and epithelial lining fluid (ELF) from patients with asthma were significantly higher than in controls, mainly due to increased leakage from the blood. Again QIgG3 were lower than Q of other subclasses. In the analysis of local production of IgG, albumin or ceruloplasmin was used as reference protein. Several patients showed a local production or a preferential accumulation of one or more IgG subclasses.We conclude that in healthy persons the IgG subclasses in ELF originate from the systemic circulation by passive permeation. In patients with asthma, the permeability of the respiratory membrane may be increased resulting in increased concentrations of subclasses in lung‐lining fluid. In some patients with asthma, an additional local production of IgG subclasses occurs.
Primary Biliary Cirrhosis (PBC): Characterization of a Monoclonal Antibody (PBC‐MoAb) having Specificity Identical with Disease‐Associated Auto‐antibodies
Authors: BJÖRKLAND A. , MENDEL‐HARTVIG I. , NELSON B. D. , TÖTTERMAN T. H. 
Published: June 2006

We have raised a monoclonal antibody (PBC‐MoAb) directed against mitochondria which resembles patent anti‐mitochondrial autoantibodies (AMA) (M2 type) in several respects.The reaction pattern of PBC‐MoAb was characterized by western blot experiments, immunoaffinity purification and enzyme inhibition studies. PBC‐MoAb reacts specifically with an epitope on the E2 suburil of pyruvate dehydrogenase (dihydrolipoamide acyltransferase) which is essential for enzymatic activity. This was shown as follows: (I) PBC‐MoAb. like PBC‐AMA, completely inhibited PDH enzyme activity and reacted weakly with OGDII; (2) PBC‐MoAb bound strongly to the E2 subunit in western blots, with weaker binding to a doublet of about 56 kDa: and O) in immunosorbent experiments, PBC‐MoAb absorbed most (>95%) 0of the AMA reactive material found in solubilized mitochondria.The present data together with earlier findings that the majority of PBC patient autoantibodies bind to epitopes defined by the PBC‐MoAb, makes this antibody a valuable tool for characterizing the major PBC‐associated epitope on PDH‐E2 and localizing this epitope in liver tissue.
Can B‐Cell Signalling be Understood?
Authors: Sinclair N. R. StC. 
Published: June 2006

Hie therefore, Robin, overcast the night; The starry welkin cover thou anon With drooping fog as black as Acheron; And lead these testy rivals so astray, As one come not within another's way.
William Shakespeare, A Midsummer Night's Dream Act III, Scene II
In Vitro Activation of Human T Lymphocytes byHaemophilus influenzaeTypebCapsular Polysaccharides
Authors: PEETERS C. C. A. M. , TENBERGEN‐MEEKES A.‐M. , HEIJNEN C. J. , POOLMAN J. T. , ZEGERS B. J. M. , RIJKERS G. T. 
Published: June 2006

Polyribosilribitolphosphate (PRP), the capsular polysaccharide fromHaemophilus influenzaetypeb, is a T‐cell‐independent type 2 antigen. In vitro culture of adult peripheral blood T cells with 15 μg/ml PRP leads to induction of interleukin‐2 receptor (IL‐2R) expression on up to 10% of T cells. These cells are CD4+and carry the αβ T‐cell receptor. PRP, at concentrations above 1–5 μg/ml, can also induce in vitro proliferation of both adult and neonatal T cells. We conclude that PRP acts as a human T‐cell mitogen.The in vitro proliferative response as well as IL‐2R expression was studied in T cells derived from adults after vaccination with native PRP, with PRP conjugated to a carrier protein, or with diphtheria toxoid. Vaccination with conjugated PRP decreased the doses of PRP required for in vitro induction of IL‐2R expression and T‐cell proliferation. This indicates that vaccination with PRP conjugated to a carrier protein improves the in vitro T‐cell response to PRP activation.
Interleukin‐4 Down‐Regulates Sendai Virus‐Induced Production of Interferon‐α and ‐β in Human Peripheral Blood Monocytes In Vitro
Authors: GOBL A. E. , ALM G. V. 
Published: June 2006

Recombinant interleukin‐4 (rIL‐4) caused a 65–70% reduction of the interferon‐α (IFN‐α) and ‐β production induced by Sendai virus (SV) in human peripheral blood monocytes in vitro. Significant inhibition was seen at concentrations as low as 0.1 ng/ml. The rIL‐4 also reduced levels of IFN‐α and ‐β mRNA by 60% and 67%, respectively, as well as the frequency of IFN‐α and ‐β mRNA‐containing cells by 65% and 54%, respectively. The frequency of IFN‐α/β mRNA‐containing cells was inhibited by rIL‐4 throughout the whole course of induction by SV. IL‐4 caused a shift of the grain count distribution towards less heavily labelled cells, suggesting an inhibitory effect of rIL‐4 on most IFN‐α/β mRNA‐containing cells. Antibodies to rIL‐4 did not influence the normal IFN‐α/β response induced by SV, but abolished the inhibitory effect of the rIL‐4.When rIL‐4 was added to cells 4 h after start of stimulation by SV, at which time much mRNA has accumulated but little IFN‐α/β has been secreted, no inhibition of the IFN‐α/β production by rIL‐4 was seen. IFN‐γ had only a minor reversing effect on the rIL‐4 inhibition, but if cells were precultivated in medium with or without IFN‐γ for 6 h before SV induction, rIL‐4 paradoxically enhanced the IFN‐α/β response.Our results suggest that rIL‐4 inhibits an early step of IFN‐α/β induction in monocytes, at the level either of transcription of IFN‐α/β genes or of the processing or stability of mRNA. The IL‐4 effects may however depend on the state of activation of the monocytes.
The Complete Amino Acid Sequence of Bovine Serum Amyloid Protein A (SAA) and of Subspecies of the Tissue‐Deposited Amyloid Fibril Protein A
Authors: ROSSEVATN K. , ANDRESEN P. K. , SLETTEN K. , HUSEBEKK A. , HUSBY G. , NORDSTOGA K. , JOHNSON K. H. , WESTERMARK G. T. , WESTERMARK P. 
Published: June 2006

Bovine serum amyloid A (SAA) was isolated from the acute phase high density lipoprotein (HDL) fraction of a cow suffering from acute mastitis. The elucidated primary structure revealed a protein consisting of 112 amino acid residues. Compared with SAA proteins from other species, the bovine protein was shown to have an insertion of nine amino acid residues between positions 69 and 70. No microheterogeneity could be observed in the protein.Amyloid fibrils extracted from the kidneys were found to contain at least three subspecies of protein AA, consisting of 68, 81 and about 110 amino acid residues. The amino acid sequences established for the protein AA subspecies revealed no microheterogeneity, and were identical to that elucidated for protein SAA.
Comparative Analysis of Syngeneic and Allogeneic Mixed Lymphocyte Reaction of ‘Naturally’ Activated and Resting T Cells
Authors: FUCS R. , DE JESUS S. A. G. , DA NOBREGA A. F. 
Published: June 2006

‘Naturally’ activated (NA) or resting T lymphocytes obtained from the spleen of normal BALB/c mice were compared in their capacity to mount a syngeneic mixed lymphocyte reaction (SMLR). Both T‐cell subsets were able to proliferate and secrete IL‐3/GM‐CSF in SMLR cultures. IL‐2 was present in ‘resting’ T‐cell SMLR supernatants, and barely detectable in NA T‐cell SMLR supernatants. Both NA and ‘resting’ T‐cell SMLRs were inhibited with anti‐class II, anti‐CD4, or anti‐IL‐2R MoAbs. NA T cells exhibited a background proliferate and secretory activity in the absence of syngeneic accessory cells. This autonomous activity was susceptible to anti‐CD4, but poorly inhibited with anti‐class II MoAbs. Both NA and ‘resting’ T lymphocytes displayed strong responsiveness to allogeneic stimuli. The analysis of the relative frequency of proliferating cells in the SMLR (BALB/c), or allo‐MLR (B10, B10.A, B10.D2) from NA or ‘resting’ T cells indicated an enrichment for syngeneic reactivity among NA T lymphocytes.The meaning of these results for NA T‐cell function and repertoire is discussed.
Effects of Immunomodulators on Ecto‐5′‐Nucleotidase Activity on Blood Mononuclear Cells In Vitro
Authors: CHRISTENSEN L. D. , ANDERSEN V. , NYGAARD P. , BENDTZEN K. 
Published: June 2006

In this study the effects of immunomodulators on the ecto‐5′‐nucleotidase (ecto‐5′‐NT) activity on blood mononuclear cells (BMC) were examined in vitro. Interleukin‐4 (IL‐4) and interferon‐γ (IFN‐γ) decreased the level of ecto‐5′‐NT activity on BMC whereas prostaglandin E2 (PGE2) increased the ecto‐5′‐NT level. All three immunomodulators influenced the ecto‐5′‐NT activity of isolated monocytes whereas only IL‐4 and PGE2 had an effect on the enzyme level on isolated lymphocytes. The effect was dependent upon protein synthesis. The effect was dose dependent: IL‐4 was effective at concentrations down to 0.5 U/ml, IFN‐γ down to 40 U/ml and PGE2 at nanomolar concentrations. These data indicate that immunomodulators may also take part in the regulation of ecto‐5′‐NT activity on BMC in vivo.BMC from 7 patients with different immunodeficiency syndromes showed decreased ecto‐5‐NT activity on freshly isolated cells. However, following culture ecto‐5′‐NT activity was increased above the level found on freshly isolated BMC from healthy persons. On BMC from 3 patients with hypogammaglobulinaemia, the effect of IL‐4 on the level of ecto‐5′‐NT activity was identical to that found on BMC from healthy donors, whereas PGE2 increased ecto‐5′‐NT activity on BMC from only 1 of the 3 patients investigated. The decreased ecto‐5′‐NT activity of BMC from patients with immunodeficiency may thus be due to a defective regulation of ecto‐5′‐NT activity