bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction of papain-digested HLA class I molecules with human alloreactive cytotoxic T lymphocytes (CTL)
Authors: HAUSMANN R , ZAVAZAVA N , STEINMANN J , MÜLLER-RUCHHOLTZ W 
Published: July 2010

SUMMARYAcute immunological rejection events of transplanted allogeneie organs are strongly dependent on T cell reactivity against foreign MHC products. The recognition requirements of alloreactive cytotoxic T cells arc of particular interest for finding approaches to modulating allorcactivity. The role of the allogeneic MHC molecule itself and/or an associated peptide in the interaction with the T cell receptor is still, however, unclear. Our studies have focused on the interactions of papain-digested HLA class I molecules with alloreactivc CD8+ CTL. These polypeptidcs, consisting of the polymorphic α1 and α2 and the monomorphic α3 domains, were used in both soluble and immobilized form to study their functional effects on anti-HLA-A2 reactive CTL. Purified polypeptides were of molecular mass 32–34 kD. HLA-A2 polypcptides (0–55 μg/ml) in soluble form induced half-maximal reduction of CTL cytotoxicity. These concentrations were quantitatively comparable to the effective doses of intact HLA class I molecules, which contain the hydrophobic transmembrane domain and the intracytoplasmic tail. In addition, specific activation requirements of these CTL were investigated in a serine esterasc release assay. Maximal degranulation was observed after 2 h of antigen contact. Purified HLA class I molecules allospccifically activated the anti-HLA-A2 CTL to degranulate serine esterase, when immobilized on plastic microtitre plates. Thus, polypeptidcs containing the polymorphic αl and α2 domains of human class I molecules potentially modulate the cytotoxic T cell response. This might have implications for the reduction or prevention of allograft rejection in recipients of foreign organs.
CR3 (CD11b, CD18): a phagocyte and NK cell membrane receptor with multiple ligand specificities and functions
Authors: ROSS G D , VĚTVIČKA V 
Published: July 2010

SUMMARYThe C3 receptor CR3 is expressed on phagocytie cells, minor subsets of B and T eells, and natural killer (NK) cells. It has important functions both as an adhesion molecule and a membrane receptor mediating recognition of diverse ligands such as intercellular adhesion molecule-1 (ICAM-1) and fixed iC3b. The receptor is capable of undergoing an activation event that regulates both its specificity for various ligands and its ability to mediate phagocytosis or extracellular eytotoxieily. Certain bacteria express earbohydrates or lipopolysaccharidcs (LPS) that can bind to and activate CR3, allowing the receptor to assume its activated state. Soluble β-glucan derived frotn the yeast Saccharomyces cerevisiae is a particularly potent stimulator of CR3, and produces an activated state of the receptor that permits neutrophil phagocytosis of iC3b-coated erytbrocytes or NK cell eytotoxicity of iC3b-coated tumour cells, tbat are normally resistant to NK cells.
Failure to detect hepatitis C virus (HCV) genome by polymerase chain reaction in human anti-HCV-positive intravenous immunoglobulins
Authors: DAMMACCO F , SANSONNO D , BEARDSLEY A , GOWANS E J 
Published: July 2010

SUMMARYThe prevalence of HCV antibodies was determined by a second-generation ELISA and a four-antigen rccombinant immunoblot assay in nine intravenous immunoglobulin (IVIG) preparations commercially available in Italy. In addition, the clinical safety of six of them was ascertained by polymerase chain reaction (PCR) of HCV RNA and a prospective study in 14 patients with immunodeficiency disorders. Results indicated that all IVIG preparations were anti-HCV-positive. However, there were substantial variations in their anti-HCV antibody titres. The preparations retained IgG subelass reactivilies to HCV-associated structural (C223) and non-structural (C33c, C100-3) proteins. Our sensitive and specific PCR assay was unable to detect HCV RNA in the six preparations tested. Clinical surveillance of IVIG-trcated patients prospectivcly evaluated over a mean period of 8·3 months failed to delect clinical and/or biochemical evidence of hepatitis.
Expression of CD5 and CD72 on T and B cell subsets in rheumatoid arthritis and Sjögren's syndrome
Authors: JAMIN C , LAMOUR A , PENNEC Y L , HIRN M , Le GOFF P , YOUINOU P 
Published: July 2010

SUMMARYA minority of B cells express the CDS marker, which is found on virtually all T cells, and CD72 has been defined as the CD5 ligand on the B cell membrane. The mean fluorescence intensity (MFI) of the CD5 molecules was shown to be higher on CD4+ CD29+ than CD4+ CD45RA+ in peripheral blood (PB) and synovial fluid (SF) of rheumatoid arthritis (RA) patients (P &lt; 0.0001 and &lt; 0.001), and PB of Sjogren's syndrome (SS) patients and normal controls (P &lt; 0·02 and &lt; 0·03). This MFI declined once the CD4 expressed HLA-DR in PB of SS patients (P 0·004) and normal controls (P 0·02) or CD25 in PB of RA (P &lt; 0·004) and SS patients (P &lt; 0·0004). There was a correlation between the CDS MFI on CD4+ CD45RA+ and CD4+ CD29+ in RA (P 0·001) as well as SS (P 0·0007) PB. The CD72 MFI was impressively higher on CD5+ than CD5 B cells in PB and SF of RA patients (P &lt; 0·0001 and P &lt; 0·005) and PB of SS patients (P &lt; 0·005) and normal controls (P &lt; 0·005). Our data suggest that, in association with CD4CD29, CD5 is involved in CD5+B/CD5+ B cell interactions in non-organ-specific autoimmune diseases.
C1 inhibitor functional deficiency in systemic lupus erythematosus (SLE)
Authors: JAZWINSKA E C , GATENBY P A , DUNCKLEY H , SERJEANTSON S W 
Published: July 2010

SUMMARY
Cl inhibitor (Cl-inh) was assayed in eight SLE patients presenting with consistently low levels of intact C4. Cl-inh antigenic levels were normal in all patients; however, the function of the Cl-inh tested against C1 s and C1 r was variable and outside the normal functional range in seven of the eight patients. The molecular weight of patients’ Cl-inh protein was 105 kD, corresponding to the size of the intact molecule. The Cl-inh gene was analysed in all patients. Restriction fragments generated with TaqI, PstI and HgiAI gave no indication of a major Cl-inh gene rearrangement. Direct genomic sequencing of exon VIII revealed three polymorphic point mutations, but there were no changes from the normal gene in or around the reactive-centre residue of Cl-inh. Furthermore, we found no evidence for a C1-inh autoantibody in patients which could affect normal Cl-inh function in vitro. These results indicate that the etiology of Cl-inh dysfunction in SLE is heterogeneous and distinct from that reported in either hereditary or acquired angioedema.
Soluble intercellular adhesion molecule-1 (sICAM-1) in sera of patients with Graves’ ophthalmopathy and thyroid diseases
Authors: HEUFELDER A E , BAHN R S 
Published: July 2010

SUMMARYIntercellular adhesion molecule, a ligand for the leucocyte integrins CDlla/CD18 (LFA-1) and CD11b/CD18 (Mac-1), that plays an important role in a variety of inflammatory and immune-mediated mechanisms, is strongly expressed in rctroocular connective tissue from patients with Graves' ophthalmopathy (GO) and involved in lymphocyte attachment to cultured retroocular fibroblasts via the ICAM-1/LFA-1-mediated pathway. Here, we report the detection and functional activity of a soluble form of the ICAM-1 molecule (sICAM-1) in sera from patients with GO and other thyroid diseases. Serum concentrations for sICAM-1 were determined using a highly sensitive ELISA. Compared with normal controls, patients with hyperthyroid or euthyroid GO and patients with Riedcl's invasive fibrous thyroiditis revealed markedly elevated sICAM-1 serum concentrations (all P 0·0001). In patients with Graves’ disease (GD) without clinical GO and in patients with Hashimoto's thyroiditis (HT), sICAM-1 levels were elevated to a lesser degree (both P &lt; 0·001). sICAVI-l serum levels in patients with non-autoimmune hyperthyroidism due to a toxic adenoma were not significantly different from normal controls. In a separate group of 12 patients with severe inflammatory GO, sICAM-1 serum levels markedly declined (P &lt; 0·0001) within 3 months of glucocorticoid therapy in nine patients who responded to this form of treatment with a decrease in periorbital inflammation. In contrast, sICAM-1 serum levels remained unchanged in three patients with poor response to steroids and persistent inflammatory periorbital disease. When tested in a cell adhesion assay, GO sera containing elevated concentrations of sICAM-1 were found to enhance the attachment of peripheral blood mononuclear cells (PBMC) to interferon-gamma (IFN-γ)-treated retroocular fibroblasts in a dose-dependent manner, up to a maximal stimulation of approximately 5×5-fold (P 0·001). This effect was abolished by preabsorption of sera with a MoAb against ICAM-1 and inhibited, in a dose-dependent manner, by coincubation with increasing concentrations of purified sICAM-1. In conclusion, sICAM-1 concentrations are markedly elevated in sera from patients with GO, and changes in sICAM-1 serum levels during glucocorticoid therapy closely parallel changes in the degree of inflammation. Given the capacity of sICAM-l to modulate the adhesion of lymphocytes to retroocular fibroblasts in vitro, sICAM-1 may play a role in the ongoing immune process within the connective tissue in GO.
Sera from patients with tuberculosis recognize the M2a-epitope (E2-subunit of pyruvate dehydrogenase) specific for primary biliary cirrhosis
Authors: KLEIN R , WIEBEL M , ENGELHART S , BERG P A 
Published: July 2010

SUMMARYAnti-M2 antibodies in primary biliary cirrhosis (PBC) have been shown to react with the alpha-ketoacid dehydrogenase complex of the inner mitochondria! membrane consisting of six epitopes (E2 subunit of the pyruvate dehydrogenase complex (PDC). 70 kD; protein X of the PDC, 56 kD; alpha-ketoglutarate dehydrogenase complex, 52 kD; branched-chain alpha-kctoacid dehydrogenase, 52 kD; Elalpha subunit of PDC, 45 kD; and Elbeta-subunit of PDC, 36 kD). These epilopes are also present in the M2 fraction which is a chloroform extract from beef heart mitochondria. The E2 subunit of the PDC at 70 kD (M2a), especially, is a major target epitope which is recognized by about 85% of all PBC sera. However, analysing sera from 28 patients with active pulmonary tuberculosis it became evident that 12 (43%) also recognized the PDC-E2 subunit (M2a), as shown by Western blotting using the M2 fraction, the purified PDC, and the rccombinant PDC-E2. In contrast, only two of 82 patients with other bacterial and viral infections including 25 patients with Escherichia coli infections reacted with the PBC-specific epilope at 70 kD. Naturally occurring mitochondrial antibodies (NOM A) were present in 54% of the patients with tuberculosis and in 50% of patients with other infectious disorders. They recognized cither a determinant at 65 kD (epsilon) or at 60/55 kD (zeta/eta). None of the sera from 100 blood donors had anti-M2 but 14 had NOM A. Testing anti-M2 and NOMA-positive marker sera by Western blotting against membrane fractions derived from mycobacteria and E. coli it could be shown that-like mammalian mitochondria—they contain both the PBC-specific M2 antigen as well as the non-PBC-specific naturally occurring mitochondrial antigen system (NOM Ag). The observation that PBC-specific antibodies were preferentially induced in patients suffering from a mycobactcrial infection may provide some new clues to the still unknown etiology of PBC.
Increased limb involvement in murine collagen-induced arthritis following treatment with anti-interferon-gamma
Authors: WILLIAMS R O , WILLIAMS D G , FELDMAISN M , MAINI R N 
Published: July 2010

SUMMARYWe have tested the effect of administering H22, a hamster neutralizing MoAb to murine interferon-gamma (IFN-γ) in collagen-induced arthritis. Mice were initTtuni7ed with human type II collagen in adjuvant on day 1 and boosted with soluble collagen on day 21. H22 was administered (250 μg. intraperitoneally) either during the induction of arthritis (on days 0, 6, 13 and 20) or around the time of discase manifestation (on days 21, 28, 35 and 42). Control mice received either an isotypc-matched non-neutralizing MoAb or saline. Both treatment regimes gave sitnilar results. Treattncnt with H22 did not signifieantly affect the incidence of arthritis, time of onset, degree of oedetiia. histopathologi-cal severity, or level of anti-type II collagen IgG. However, a highly signiticanl increase (P &lt; 0·01) in the number of limbs affected by arthritis was observed in the H22-treated group, irrespective of whether the antibody was administered during the induction of arthritis, or during the time of clinical manifcstalion of disease. From these results it was concluded that anti-IFN-γ treatment caused an inerease in the niitnber of arthritic lesions, but did not affect the severity of each individual lesion.
Inhibition by glucocorticoid and staurosporine of IL-4-dependent CD23 production in B lymphocytes is reversed on engaging CD40
Authors: KATIRA A , KNOX K A , FINNEY M , MICHELL R H , WAKELAM M , GORDON J 
Published: July 2010

SUMMARYIL-4 synergizes with signals delivered through CD40 both for the induction of CD23/FcRH expression and for IgE synthesis. Moreover, engagement of CD40 on the B cell surface by MoAb overcomes the ability of intcrferons. transforming growth factor-beta, or anti-CD 19 to inhibit IL-4-dependent change. We now report that occupancy of CD40 relieves potent suppression of IL-4-induced CD23 production by glucocorticoid or the relatively broad-acting kinase inhibitor staurosporine. Interruption of the IL-4 signal was observed with concentrations of staurosporine considered to be selective for protein kinase C (PKC) inhibition (IC50= 10 nm) but not with genistein or tyrphostins. effective inhibitors of tyrosine kinase activity. On ligation of CD40, staurosporine no longer inhibited the IL-4 signal: at concentrations of between I and 20 nM. staurosporine actually increased by as much as 100% the rate of CD23 production stimulated on simultaneous activation through CD40 and 1L-4R. Such augmentation was not observed when the more specific PKC inhibitor RO-31-8220 was used; indeed. CD40 engagement was unable to overcome the ability of this inhibitor to block IL-4-promoted CD23 induction (IC50= 10 μm). Occupancy of CD40 did, however, thwart completely the usual ability of prednisolone to inhibit the IL-4 signal leading to CD23 induction. Activation through CD40 left inhibition of phorbol ester-induced CD23 expression by staurosporine, RO-31-8220, or glucocorticoid unchecked. These findings further highlight the intimate level of cross-talk existing between CD40 and IL-4R on resting B lymphocytes to promote CD23 expression, a phenotypic change which preludes IgE synthesis.
Antibodies to the CD5 molecule in normal human immunoglobulins for therapeutic use (intravenous immunoglobulins, IVIg)
Authors: VASSILEV T , GELIN C , KAVERI S V , ZILBER M-T , BOUMSELL L , KAZATCHKINE M D 
Published: July 2010

SUMMARYTVIg are increasingly used Tor the treatment of autoimmune diseases. In the present study, we show thai IVIg contain antibodies directed againsl CD5, a cell surface molecule of T cells which is also a marker of the autoantibody-producing CD20+(‘B-r) subset of B lymphocyies, Antibodies to the CD5 molecule were demonstrated in IVIg by the ability of therapeutie preparations of IVIg to inhibit the binding of labelled CD5 MoAh to ihe CD5-expressing human Tcell lineH9. Prcincubation of H9 cells with IVIg or with F(ab')2 fragments prepared from IVIg resulted in dose-dependent inhibition nf the binding of CDS antibody. The presence in IVIg of antibodies to the CD5 molecule was fiirther confirmed by the binding of IVIg to mouse L cells that expressed human CD5 molecules following a stable transfeetion with CD5 cDNA. Human CD5 antibodies in IVIg provide therapeutic immunoglobulin preparations with the potential of modulating Tcell functions through CD5. and of regulating the expression of B cell subsets expressing CD5. This may have impliealions for the treatment of autoimmune diseases.
Anti-LKM-1 antibodies determined by use of recombinant P450 2D6 in ELISA and Western blot and their association with anti-HCV and HCV-RNA
Authors: SEELIG R , RENZ M , BÜNGER G , SCHRÖTER H , SEELIG H P 
Published: July 2010

SUMMARYSeveral subtypes of anti-liver-kidney microsome antibodies (LKM) are known, LKM-1 antibodies associated with autoimmune chronic active hepatitis recognize P450 2D6, a cytochrome P450 monooxygenase. The frequent association of anti-LKM-l antibodies and hepatitis C virus (HCV) infections and the probable existence of an infectious and autoimmune form of anti-LKM-l-associated hepatitis, requiring different therapeutical strategies, necessitates the exact determination of anti-LKM-1 specificities. Therefore, we compared various antibody tests (immunofluorescence. ELISA with recombinant P450 2D6, and Western blot with recombinant and natural antigens and agargel double diffusion) with sera of 27 anti-LKM-1-positive chronic active hepatitis (CAH) patients, with 61 sera harbouring anti-mitoehondrial antibodies, 100 sera each from HCV-RNA-positive and HCV-RNA-negative patients, and 50 sera of healthy persons. Western blot techniques using recombinant MS2-polymcrase P450 2D6 fusion protein were found to be the most sensitive and specific method for anti-LKM-1 antibody determination in routine laboratory. The recently recognized association of anti-LKM-l antibody and HCV infection was confirmed by the results of this study. In anti-HCV and HCV-RNA-positive patients with anti-LKM-1 antibodies there was a preponderance of males with higher mean age and lower antibody titres. The results support the hypothesis of the existence of an autoimmune as well as an infectious (HCV triggered) subgroup of anti-LKM-l-positive hepatitis.
The B cell repertoire of patients with rheumatoid arthritis. Frequencies and specificities of peripheral blood B cells reacting with human IgG, human collagens, a mycobacterial heat shock protein and other antigens
Authors: RUDOLPHI U , HOHLBAUM A , LANG B , PETER H H , MELCHERS I 
Published: July 2010

SUMMARYUsing a potent in vitro limiting dilution culture system, we have activated human peripheral blood B cells to proliferate and to differentiate into antibody-secreting cells (ASC). Under these conditions 25–100 % of B cells are clonally expanded and produce IgM, IgG or IgA. Culture supernatants were tested for antibodies binding to human IgG-Fc fragments (RF), the 65-kD heat shock protein of Mycobacterium bavis (hsp60), human collagens type I, II, IV, V, transferrin, lactoferrin, albumins, and gelatine. All blood samples contained precursors of ASC (p-ASC) able to produce IgM binding to these antigens in frequencies above 003% of B cells. Most interestingly, a significant difference exists between rheumatoid arthritis (RA) patients and controls, concerning the relative frequencies of p-ASC able to produce monospecific or multircactive RF. Whereas most p-ASC(RF) in RA patients are monospecific (mean ratio 3.7), most p-ASC(RF) in healthy control persons are cross-reactive with at least one of five other antigens tested (mean ratio 0.2). The data suggest a disease-specific expansion of p-ASC committed to the production of monospecific rheumatoid factors.
Correlative studies of rheumatoid factors and anti-viral antibodies in patients with rheumatoid arthritis
Authors: FERRARO A S , NEWKIRK M M 
Published: July 2010

SUMMARYAn analysis of the relationship between the immune response to ubiquitous herpes family viruses, namely Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella-zoster virus (VZV) and the presence of rheumatoid factors (RF), which are autoantibodics characteristic of patients with rheumatoid arthritis (RA), was conducted. Antibody profiles (RF, anti-viral antibodies) were monitored in the serum of the RA patients, and in normal individuals. No patient was found to have circulating RF in the absence of anti-viral antibodies. When the patients and normal controls were subdivided according to the presence of serum RF, it was found that when RF were present, the frequency of anti-CMV antibodies, but not anti-EBV or anti-VZV antibodies, was significantly higher (P= 0.02) when compared with RF-negative individuals. The litres of anti-CMV but not anti-VZV antibodies were found to increase in the RA patients with disease duration. To see if these viruses could stimulate RF production in vitro, peripheral blood mononuclear cells (PBMC) isolated from the patients and normal controls were stimulated with viral antigens. PBMC from normal controls, but not from RA patients, appeared to be responsive to viral antigen stimulation and produced RF. These data suggest that the immune response to CMV, to a greater extent than to EBV or VZV, correlates with the presence of RF.
Loss of mucosal CD4 lymphocytes is an early feature of HIV infection
Authors: LIM S G , CONDEZ A , LEE C A , JOHNSON M A , ELIA C , POULTER L W 
Published: July 2010

SUMMARYT cell subsets in the gut mucosa are distinct populations and their imbalance in HIV has specific implications in infection. Alterations in T cell subsets in duodenal biopsies were investigated in 17 asymptomatic HIV patients, 24 AIDS patients and 10 controls with non-ulcer dyspepsia. Immunohistochemistry and immunofluoresccnce using MoAbs to CD3, CD4, CDS, CD68, CD45R A, CD45RO and gp 120 were performed on frozen sections. In the lamina propria. there was a significant depletion of CD4+ cells at all stages of HIV, but the density of CDS lamina propria cells was increased. Intraepithelial lymphocytes were decreased in AIDS patients. There was a significant correlation between cellular density and mucosal CD3+ lymphocytes, and between mucosal CD3+ and CDS+ lymphocytes. Although mucosal CD4, CD45RO+‘memory’ cells were decreased, CD8.CD45RO+‘memory’ cells were increased. Mucosal CD4+ lymphocyte depletion occurred early in HIV, and thus their role in mucosal protection against opportunistic infection should be revised. Mucosal CD8+ lymphocytes initially increased, but decreased when CD4 blood counts were depleted, perhaps contributing to loss of host protection against infection. Intraepithelial lymphocyte depletion may also contribute to opportunistic infection.
Characterization of anti-acetylcholine receptor (AChR) antibodies from mice differing in susceptibility for experimental autoimmune myasthenia gravis (EAMG)
Authors: GRAUS Y M F , van BREDA VRIESMAN P J C , de BAETS M H 
Published: July 2010

SUMMARYIn the murine model for EAMG we investigated the relation between disease susceptibility and fine specificity of anti-AChR antibodies obtained from high susceptible C57BI/6 and low susceptible BALB/c mice after immunization with Torpedo acetylcholinc receptor (tAChR). Anti-AChR MoAbs with fine specificity for the main immunogenic region (MIR), the α-bungarotoxin (α-BT)/ acetylcholine binding sites and other extra- and intracellular epitopes were isolated from both mouse strains. In total, nine out of 38 MoAbs obtained from C57BI/6 mice were directed against extracellular epitopes on mouse AChR in contrast to only one out of 27 MoAbs from BALB/c mice. A difference in antibody repertoire may underlie the difference in pathogenic response observed between these mouse strains. These results indicate that strain-specific differences in disease susceptibility in murine EAMG may be related to differences in the available repertoire of potential pathogenic antibodies.