bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiparametric Flow Cytometric Analysis of the Kinetics of Surface Molecule Expression after Polyclonal Activation of Human Peripheral Blood T Lymphocytes
Authors: BISELLI R. , MATRICARDI P. M. , AMELIO R. D. , FATTOROSSI A. 
Published: June 2006

In this report we have analysed the kinetics of modulation of human peripheral blood T lymphocyte membrane molecules upon activation with optimal amounts of phytohaemagglutinin (PHA) and concanavalin A (ConA). The following activation‐related and differentiation/adhesion molecules were selectively and concomitantly investigated on CD4+ and CD8+ subsets by dual colour flow cytometry: CD69, CD25 and CD71; CD2, CD45RA and L‐selectin. Cultures were assayed after 24, 48. 72. 120 and 168 h of incubation with PHA and ConA. This approach allowed a comprehensive evaluation of membrane phenomena occurring during activation of normal resting human T lymphocytes. Data show that the kinetics of expression of these molecules follows a precise and consistent time‐course with no major differences between CD4 and CD8 subsets. CD69 expression peaked at 24 h. whereas CD25 and CD71 expression peaked al 48/72 h with some differences between PHA and ConA activation. L‐selectin expression started an evident decrease in step with culture time whose magnitude was dependent on the lectin used, being higher with PHA than with ConA. Conversely, the expression of CD45RA remained stable for 72 h and then briskly decreased with no major differences between PHA and ConA activation. CD2 molecules increased with time in number and density, although the percentage of positive cells remained essentially constant (>85%). After 48/72 h of stimulation about 10% of cells co‐expressed CD4 and CD8 molecules. To ascertain whether the phenomenon was restricted to cells in a particular activation state, the phenotype of cells in the diverse phases of the cell cycle was established. Results obtained show that only actively proliferating cells, that is cells in S and G2‐M phases, co‐expressed the two molecules, suggesting that such a phenomenon reflects a momentary dysregulation of the normal sequence of gene expression.The present data are also discussed in the light of the dynamic role of T lymphocyte activation and adhesion molecules in regulating cell‐cell interactions, tissue localization and eventual immunological function.
Inhibition of Interleukin‐1 (Alpha and Beta), Interleukin‐2 Secretion and Surface Expression of Interleukin‐2 Receptor (IL‐2R) by a Novel Cytokine Interleukin‐1 Receptor Antagonist (IL‐lra)
Authors: CONTI P. , PANARA M. R. , PORRINI A. M. , GAMBI D. , BARBACANE R. C. , REALE M. , BONGRAZIO M. , DEMPSEY R. A. 
Published: June 2006

IL‐1 is a mediator of the acute inflammatory response and plays a key role in influencing growth and differentiation of immunocompetent lymphocytes. It can enhance transcription and secretion of the T‐cell growth factor interleukin‐2 (IL‐2) and can stimulate the expression of membrane receptors for IL‐2. However, the regulation and control of IL‐1 activities are poorly understood. Recently an IL‐1 inhibitor, interleukin‐1 receptor antagonist (IL‐1ra), has been described and cloned. This protein is a monokine originally found in the urine of febrile patients and in supernatants of human monocytes adhering to an IgG‐coated surface, with an approximate molecular weight of 17 kDa, which is similar to IL‐1β but having no IL‐1‐like activity and antagonizing IL‐1 by binding to its cell surface receptor.These studies have examined some biological properties of hrIL‐1ra, such as its effects on the secretion of IL‐1α or IL‐1β and IL‐2, the surface expression of 1L‐2R and DNA synthesis by peripheral blood mononuclear cells (PBMC). PBMC from normal volunteers were separated and used at a concentration of 2.5 x 106 cells/ml. The cells were pretreated for 2h with hrIL‐1ra (0.025‐250 ng/ml), treated with LPS (10 ng/ml), and IL‐1α and IL‐1β secretion were determined by an ELISA method. In addition the influence of hrIL‐1ra (25 ng/ml) on IL‐2 generation was determined. In another set of experiments, flow cytometric analysis with an anti‐CD25 monoclonal antibody was determined on PHA‐stimulaled PBMC pretreated wilh hrIL‐1ra (2 h) and cultured for 48 h. The inhibition by hrIL‐1ra of IL‐2R expression was dose‐dependent and when hrIL‐1ra was used at 250 ng/ml the IL‐2R was completely abolished. Lymphocyte DNA synthesis calculated from the net uptake of [3H]‐thymidine (3H‐TdR) was also inhibited by hrIL‐1ra (0.025‐25 ng/ml). In this report we found that hrIL‐1ra inhibits, in a dose‐dependent manner, the secretion of IL‐1α, IL‐1β, IL‐2, the surface expression of IL‐2R and 3H‐TdR incorporation in PBMC in vitro. These data suggest a new biological activity of hrIL‐1ra and further extend the immunomodulatory potential and significance of this new cytokine. The action of IL‐1ra on modulating the synthesis of IL‐1 may be of paramount importance in the regulation of these effects.
Immunoglobulin G, A, and M Light Chain Ratios in some Humoral Immunological Disorders
Authors: HARALDSSON Á. , JAMINON M. , BAKKEREN J.A.J.M. , STOELINGA G. B. A. , WEEMAES C. M. R. 
Published: June 2006

The total kappa/lambda immunoglobulin light chain ratio and the kappa/lambda ratios within each of the serum immunoglobulin classes G. A. and M were measured in thirteen patients with humoral immunological disorders. Of those patients, eight had common variable immunodeficiency whereas live patients had other forms of humoral immunological deficiencies. Eleven patients had abnormal antibody response in vivo. All but three of the thirteen patients had clearly abnormal light chain ratios in one or more of the immunoglobulin classes.We conclude that humoral immunological disorders, usually characterized by abnormal heavy chain production and a disturbed antibody response, may frequently have a concomitant abnormal synthesis of the light chains resulting in an abnormal kappa/lambda light chain ratio.
Reactivity of γδ T Cells Induced by the Tumour Cell Line RPMI 8226: Functional Heterogeneity of Clonal Populations and Role of GroEL Heat Shock Proteins
Authors: SELIN L. K. , STEWART S. , SHEN C. , MAO H. Q. , WILKINS J. A. 
Published: June 2006

The human tumour cell lines RPMI 8226 and Daudi are potent inducers of Vγ9‐expressing T cells. The inducing element of RPMI 8226 has not been defined but evidence suggests that a member of the GroEL heat shock protein (HSP) family (HSP 58) may have a role in the induction by Daudi cells. The present study examined the reactivity patterns of γδ T‐cell clones generated in response to RPMI 8226 and addressed the possible rule of MSP 58 in this process.RPMI K226 induced a population of Vγ9 TCR+ cells which were heterogeneous in terms of their cell surface markers, patterns of proliferation and cytotoxic responses. All clones expressed CD3, CD2, CD18 and CD29). They demonstrated variability in expression of CD56, CD8 and HLA‐DR. RPMI 8226 stimulated proliferation in purified bulk γδ cultures and clones. Daudi was also capable of inducing these cells to proliferate while mycobacterial products were not effective. The clones demonstrated a limited non‐MHC‐restricted cytotoxicity pattern with some evidence of clonal heterogeneity. Although both Daudi and RPMI 8226 were sensitive to lysis by the clones, cold inhibition experiments indicated differential activity towards these targets.Anti‐HSP 58 was inhibitory to γδ T‐cell induction by RPMI 8226, Daudi and mycobacterial products. However, the anti‐HSP 58 antibody appears to bind to the surface of at least six different tumour cell lines with no correlation to their ability to induce γδ cells and the anti‐HSP 58 inhibited non‐γδ responses.
Effect of rIFN‐γ on Antibody‐Mediated Cytotoxicity via Human Monocyte IgG Fc Receptor II (CD32)
Authors: VAN SCHIE R. C. A. A. , VERSTRATEN H. G. G. , TAX W. J. M. , VAN DEN BERKMORTEL F. W. P. J. , VAN DE WINKEL J. G. J. , DE MULDER P. H. M. 
Published: June 2006

Human monocytes and macrophages express an isoform of IgG Fe receptor II (FcγRII), FcγRII. Two allotypic variants of this receptor could be distinguished with respect to their ability to bind murine (m)IgG1 complexes either strongly or weakly, defined as high‐responder (HR) and low‐responder (LR). respectively. We investigated the effect of recombinant (r)IFN‐γ on the ability of freshly isolated monocytes, and those cultured for 40 h and 9 days, to mediate antibody‐dependent cell‐mediated cytotoxicity (ADCC), Using human erythrocytes (E) sensitized with mlgGl as target cells, FcγRII was studied selectively. Cells which had been cultured for 40 h exhibit a significantly decreased FcγRII expression, and FcγRll‐mediated ADCC activity as compared with freshly isolated monocytes. Co‐culture with rlFN‐γ (40 h) reversed this decrease. Short‐term rlFN‐γ‐cultured cells, and fresh cells express similar numbers of FcγRII, and exhibit comparable FcγRII‐mediated ADCC activity. Phagocytic activity was not affected. Prolonged culture of monocytes for 9 days, co‐cultured with rlFN‐γ either from day 0 or from day 7, did not affect expression or functional activity of FcγRII. Furthermore, the effects were observed in both HR and LR individuals.Our results show that rlFN‐γ has strong effects on FcγRII‐mediated responses specifically during the early stages of monocyte maturation, most likely by affecting receptor expression levels.
Lymphocyte Recirculation: the Need for Site‐Specific Receptors to Dictate T‐Lymphocyte Localization into Different Tissue Sites
Authors: Frogner Fredrik J. , O'Neill Helen C. 
Published: June 2006

SummaryThis paper addresses the need for receptors involved in recirculation of T lymphocytes both during development and during an immune response or inflammation. Some known receptors present on T lymphocytes which are important in maintaining normal T‐cell localization and function, i.e. the integrins, LECAMs, LPAM‐1 and H‐CAM (CD44) are considered in terms of the specificity which they confer on lymphocyte recirculation. A clear understanding of lymphocyte trafficking patterns and of the receptors involved may provide, for example, novel therapies for treatment of malignant cancer, alleviation of damage caused by lymphocytes during inflammatory responses, and targeting of cells to sites of infection.
Spontaneous IgM Autoantibody Production In Vitro by B Lymphocytes of Normal Human Neonates
Authors: BARBOUCHE R. , FORVEILLE M. , FISCHER A. , AVRAMEAS S. , DURANDY A. 
Published: June 2006

Human neonate B lymphocytes display unique phenotypic and functional characteristics: in addition to CD1c antigens, CD5+ and CD5‐ subsets both express activation markers such as CD23 and Bac‐1. They proliferate strongly in the presence of various lymphokines (rIL‐2, rIL‐4, low molecular weight BCGF), but differentiate poorly in the presence of the same lymphokines, pokeweed mitogen and Epstein Barr virus. It has also been reported that human neonate B lymphocytes produce polyreactive autoantibodies after in vitro activation by Staphylococcus aureus Cowan I and transformation by Epstein Barr virus. We now show that, in the absence of in vitro stimulation, human neonate B lymphocytes produce polyreactive antibodies of the IgM isotype against several autoantigens. The B lymphocytes involved expressed membrane IgD, IgM, CD23 and CD11b molecules; CD5 expression was variable. This phenotype was consistently found on a minority of B lymphocytes and is similar to that of polyreactive autoantibody‐producing B cells in mice. We also found that autoantibody production in vitro could occur in the absence of any T helper effectThe function of these autoantibodies is not clearly established, but their occurrence in a large proportion of human neonates strongly suggests that they play an important role in the development of the immune system.
Control of Trypanosoma cruzi Infection in Mice Deprived of T‐Cell Help
Authors: ROTTENBERG M. E. , RODRIGUEZ D. A. , ÖRN A. 
Published: June 2006

The role of CD4+ T lymphocytes in the resistance of BALB/c mice to Trypanosoma cruzi was examined by in vivo depletion using monoclonal anti‐CD4 antibodies (MoAbs)<. When the administration of MoAbs was initiated 2 days before, or 5 to 12 days after the infeetion (dpi) with 50 bloodstream‐from trypomastigotes of the Tulahun strain, mice showed an enhanced susceptibility to the parasite. Speeific IgM. but not IgM responses, were inhibited in anti‐CD4‐treated and infected miceHowever, when anti‐CD4 treatment of mice was delayed until the 8th week of infection. neither a reactivation of the infection as determined by mortality or parasitaemia. nor a modulation of the titre of anti‐ T. cruzi IgG antibodies was detected. Furthermore, mice chronically infeeted with T. cruzi and deprived of CD4 or T cells resisted the challenge with 50,000 trypomastigotes (approximately 1000 LD50)Secondary antibody responses against parasite antigens were inhibited after in vitro depletion of CD4+ cells in chronically infected mice before boosting with T. cruzi antigens. However, recipients of CD4 or T‐cell‐depleled spleen cells from mice chronieally infected with T. cruzi were protected when challenged with the parasiteThe possibility that the parasite control is maintained by long‐lived B cells capable of rapid differentiation into IgG‐secreting plasma cells in the absence of T helper cells is discussed considering the present data
Aberrations in Titre and Avidity of Serum IgM and IgG Antibodies to Microbial and Food Antigens in IgA Deficiency
Authors: CARDINALE F. , FRIMAN F. , CARLSSON B. , BJÖRLKANDER J. , ARMENIO L , HANSON L. Å. 
Published: June 2006

The antibody levels and relative avidity of serum IgM and IgG aniibodies against E. coli O antigens, poliovirus type 1 and /J‐lactoglobulin were determined with enzyme‐linked immunosor‐bent techniques in IgA deficient (IgAd) patients with frequent respiratory tract infections an d healthy IgAd individuals. Heallhy individuals with normal tmmunoglobulin levels served as controls.The IgM antibody levels against the bacterial, viral and food antigens and the IgG antibody levels against the bacterial antigens were significantly higher in the IgAd group with recurrent infections than in the group of healthy IgAd individuals. The symptomatic IgAd group had significantly higher levels of the IgG antibodies against the bacterial antigen, also when eompared with controls.In contrast the healthy IgAd individuals had the highesi avidities of IgM antibodies to the viral and food antigens. The high avidities of aniibodies could be a compensatory host defence mechanism in IgAd.These aberrations may appear as a consequence of increased mucosal exposure in IgAd to antigens such as E. coti or/f‐lactoglobulin. but presumably not to poliovirus which is only exceptionally present in the milieux. They could also be a result of the previously suggested dysregulation of antibody responses in IgAd.
A Family of Cross‐Reacting Proteins Secreted by Mycobacterium tuberculosis
Authors: WIKER H. G. , NAGAI S. , HARBOE M. , LJUNGQVIST L. 
Published: June 2006

Cross‐reactions between live proteins actively secreted by Mycohacierium tuberculosis were studied by crossed immunoelectrophoresis, SDS ‐PAGE with immuiioblotting. and ELISA using polyelonal rabbit aniisera and mouse monoclonal aniibodies to the purified proteins. The monoclonal antibody HBT4 was demonstrated to react with the MPT5I protein. The 85A, 85B and 85C constituents of the M. tuberculosis and Mycobacterium bovis BCG antigen 85 complex cross‐react extensively, each of the components containing component‐specific as well as cross‐reacting epilopes. These components also cross‐reacted with MPT5I and MPT64.N‐terminal sequence studies revealed striking homology at the amino acid level between 85A, 85B, 85C and MPT51, MPT64 showed less homology. In addition, striking homology was demonslraled between two diflerent stretches within the K5B sequence and indicated between three siretches within the MPT64 molecule. Thus, a family of at least four secreted proteins with common structural features has been demonstrated in mycobacteria, MPT64 may also belong to this family
Analysis of HLA Genotypes and Susceptibility to Insulin‐Dependent Diabetes Mellitus: Association Maps Telomeric to HLA‐DP
Authors: BAISCH J. M. , CAPRA J. D. 
Published: June 2006

There is convincing evidence that certain combinations of alleles within the human leucocyte antigen (HLA) complex, particularly within HLA‐DQ, are associated with either resistance or susceptibility to insulin‐dependent diabetes mellitus (IDDM). A previous study conducted on a large, well‐defined grou p of patients demonstrated that DQB 1*0302 (DQw8) conferred ‘dominant susceptibility’ to IDDM while DQB 1*0602 (DQwl.2) conferred ‘dominant protection’. The availability of this population enabled us to further assess susceptibility associated with other class II alleles in an effort to map an outside HL A boundary of disease association. Using a group‐specific polymerase chain reaction protocol and a series of oligonucleotide probes which define over twenty DPβ alleles, we studied 286 unrelated Caucasian patients with IDDM and 184 normal subjects.We found that while several alleles are increased (DPB1*0201, DPB1*0301, DPB1*0402) or decreased (DPB1*0101, DPB1*0202) in the diabetic population compared with the normal subjects, the HL A association with IDDM is considerably weaker at the DP locus. These data define the centromeric boundary for the HLA‐associated susceptibility gene in IDDM, localizing susceptibility to the region telomeric to HLA‐DP up to and including HLA‐DQ
Hypothesis for the Control of Clotting Factor VIII Inhibitory Antibodies by Decreasing Potency of Helper T‐Cell‐Recognized Epitopes in Factor VIII
Authors: Tiarks C. , Humphreys R. E. , Anderson J. , Mole J. , Pechet L. 
Published: June 2006

SummaryThe study of the immunobiology of FVIII inhibitors may lead to new therapies for this potentially severe complication of haemophilia A and to new principles for the use of therapeutic proteins. In order to characterize the idiotype‐anti‐idiotype networks regulating FVIII inhibitors, we developed rabbit antiidiotypic sera to 7 murine inhibitors and found at least 12 independent FVIII loci to which inhibitors could be raised. Rabbit antisera to the FVIII peptide. Ser1687‐Thr1695 characterized one functional site to which about 46% of patients' inhibitor sera reacted. The multiplicity of inhibitor‐recognized epitopes in FVIII makes it impractical, at the present time, to develop clinically useful specific anti‐idiotypic therapies for FVIII inhibitors. Alternatively, one might induce genomic mutations in recombinant FVIII molecules to decrease immunogenicity of epitopes recognized by T helper cells. Methods to design such altered therapeutic proteins are presented, based on changing the longitudinal hydrophobic strip of‐helix which is in or near many T‐cell‐presented epitopes.
Adhesion Molecules Involved in the Interaction of LGL/NK Cells and Human Endothelial Cells Stimulated with Salmonella Bacteria
Authors: PINOLA M. , SAKSELA E. 
Published: June 2006

Previously we showed that pretreatment of LGL/NK or HUVE cells with Salmonella bacteria augments the adhesion of LGL/NK cells to endothelium. Here we analyse the roles of HUVEC adhesion molecules VCAM‐l, ICAM‐I and E‐selectin, and the counter‐receptors VLA‐4, LFA‐1 and SLe3 in the increase of LGL/NK adhesion to HUVEC, stimulated with Salmonella Minnesota mR595 bacteria. LPS or TNF‐α.On salmonella‐stimulated HUVEC, VCAM‐l and ICAM‐1 were the major binding structures involved, and their effect was additive in monoclonal antibody inhibition experiments. We could demonstrate the induction of both structures on cultured HUVEC after 24 h of Salmonella stimulation in flow cytometric analysis. For salmonella‐stimulaled LGL/NK, the principal binding structure was LFA‐1, Stimulation of LGL/NK cells did not alter the expression of the adhesion structures (subunits CD11a/CD18, CD49d/CD29). as determined by flow cytometric analysis, and thus the increased adherence is presumably produced by an increased avidity of the receptors on LGL/NK cells.Pretreatment of endothelium or lymphocytes with various stimuli, including Salmonella bacteria or LPS, leads to an activation state which provides for characteristic anchorage sites for the increased migration of LGL/NK cells towards the site of inflammation.
T‐Cell Receptor V‐Gene Usage in Synovial Fluid and Synovial Tissue from RA Patients
Authors: GUDMUNDSSON S. , RÖNNELID J , KARLSSON‐PARRA A. , LYSHOLM J. , GUDBJÖRNSSON B. , WIDENFALK B. , JANSON C. H. , KLARESKOG L. 
Published: June 2006

The question of whether there is a preferential use of certain V genes in T cells entering an inflamed joint has hitherto been studied mainly using unfractionated cells from synovial fluid and tissue respectively, and no clear answer to the question has yet been provided. Concomitantly. evidence has been provided that the use of V genes may differ considerably between CD4+ and CD8+ T cells, and consequently that detection of biased V‐gene expression within an inflammatory lesion may require separate analysis of the two T‐cell subsets.In this paper we have therefore studied T‐cell receptor V‐gene expression in rheumatoid arthritis by means of double stainings of synovial fluid and blood for available anti‐TCR monoclonal antibodies and antibodies to CD4 and CD8. respectively. Double stainings were also performed with anti‐TCR antibodies and antibodies to activation markers HLA‐DR and 1L‐2R. A certain bias towards the preferential use of certain V genes was seen particularly in the synovial fluid samples within both the CD4+ and CD8+ T‐cell populations, but no uniform pattern was evident among the 35 patients investigated.
Interleukin 4 and Tumour Necrosis Factor α Induce Different Adhesion Pathways in Endothelial Cells for the Binding of Peripheral Blood Lymphocytes
Authors: GALÉA P. , LEBRANCHU Y. , THIBAULT G. , BARDOS P. 
Published: June 2006

We demonstrated that tumour necrosis factor α (TNF‐α) and interleukin 4 (IL‐4) increased endothelial cell (EC) adhesiveness for peripheral blood lymphocytes (PBL) by promoting transcription and protein synthesis. Theo different kinetics observed with TNF‐α and IL‐4 suggest the involvement of different adhesion molecules.Blocking adhesion assays and immunofluorescence analysis showed that PBL adhesion to endothelial cells involves different pair adhesion molecules. Whereas IL‐4 promoted an LFA‐1‐dependent/ICAM‐1‐independent adhesion pathway on EC, TNF‐α stimulated an LFA‐1‐dependent/ICAM‐1‐dependent adhesion pathway on EC. In conttast. VLA‐4/VCAM‐1 molecules were involved in PBL adhesion both to IL‐4 and to TNF‐α‐stimulated EC. Finally, we found that a CD2‐dependent/LFA‐3‐independent adhesion pathway was mainly involved in IL‐4‐stimulated EC.