bluuebunny/crossref_metadata_2025_split huggingface dataset:
Duodenal intraepithelial γ/δ T cells and soluble CD8, neopterin, and β2-microglobulin in serum of IgA-deficient subjects with or without IgG subclass deficiency
Authors: NILSSEN D E , AUKRUST P , FRØLAND S S , MÜLLER F , FAUSA O , HALSTENSEN T S , BRANDTZAEG P 
Published: July 2010

SUMMARYExpression of the γ/δ T cell receptor (TCR) on CD3+ intracpithclial lymphocytes (IELs) was studied by two-colour immunofluorescence in duodenal tissue sections from healthy (n= 6) or infection-prone (n = 7) subjects with selective IgA deficiency (IgAD), and subjects (n = 4) with combined IgAD and IgG subclass deficiency. TCRγ/δ+ IEL proportions in selective IgAD subjects (median 6·3%, range 1·0–41%) and in those with combined deficiency (median 4·5%, range 1±2·33%) were well within the range (0·3–38%) for histologically normal controls (n= 11), but the healthy IgAD subgroup tended to show raised TCRγ/δ+ IEL proportions (median 13·6%) compared with the other two subgroups. Also the number of TCRγ/δ+ IELs per intestinal length unit was relatively high (median 13·9/mm) in the healthy IgAD subjects, and significantly raised (P &lt; 0·03) compared with controls (median 3·2/mm). Paired staining revealed that most TCRγ/δ+ IELs in both selective IgAD (98%) and combined deficiency (99%) were CD8, and a large fraction (median 84% and 63%, respectively) expressed the Vδ1/Jδ1-encoded epitope. The total number of CD3’ IELs (mostly CD8+) was similar to controls. IgAD subjects, and especially the healthy subgroup, had significantly increased serum concentrations of soluble CD8 (P &lt; 0·0002), neopterin (P &lt; 0·005), and β2-microglobulin (P &lt; 0·007). which was similar to our previous observations in common variable immunodeficiency, and probably reflected stimulation of cell-mediated immunity. In addition, the increased TCRγ/δ+ IELs might reflect a component of compensatory surface protection in the healthy IgAD subgroup.
Mannan-binding protein—levels in plasma and upper-airways secretions and frequency of genotypes in children with recurrence of otitis media
Authors: GARRED P , BRYGGE K , SØRENSEN C H , MADSEN H O , THIEL S , SVEJGAARD A 
Published: July 2010

SUMMARYWe have investigated a possible association between recurrence of olitis media and low concentrations of mannan-binding protein (MBP) in plasma and upper-airway secretions. The protein concentration was measured in plasma (n= 76), nasopharyngeal secretions (n= 83) and middle ear effusions (n= 73) from otitis-prone children, children with less recurrence of acute otitis media, children with no previous history of acute otitis media, but suffering from secretory olitis media, and healthy children. Moreover, genetic polymorphisms associated with low MBP plasma levels were investigated in DNA from nasopharyngeal tonsils of 89 children with recurrence of otitis media. A wide range of M BP plasma concentrations was found. No statistically significant differences in M BP plasma concentration were observed between patients and controls. Nor was there any increased frequency of the genotypes associated with low MBP plasma concentrations. Thus, our results do not support the assumption that low concentration and/or MBP deficiency alone predispose to recurrence of otitis media in Caucasian children. MBP was detected in both nasopharyngeal secretions (1/175 of plasma level) and middle ear effusions (1/4 of plasma level), suggesting a role for the protein in the local mucosal immune defence system at these locations. In contrast. MBP was undetectable in 53 samples of mixed-saliva.
Modulation of adhesion molecule expression on endothelial cells during the late asthmatic reaction: role of macrophage-derived tumour necrosis factor-alpha
Authors: LASSALLE P , GOSSET P , DELNESTE Y , TSICOPOULOS A , CAPRON A , JOSEPH M , TONNEL A B 
Published: July 2010

SUMMARYIn a previous work we have demonstrated that in patients exhibiting a late allergic reaction (LAR), alveolar macrophages (AM) collected 18 h after bronchial allergen challenge produced high levels of IL-6 and tumour necrosis factor-alpha (TNF) which is known to up-regulate the endothelial cell expression of adhesion molecules participating in the development of the inflammatory reaction in bronchial asthma. For these reasons, we evaluated the effect of AM supernatants from asthmatic patients developing an LAR on intercellular adhesion molecule-1 (ICAM-1) and endothelial leucocyte adhesion molecule-1 (ELAM-1) expression by human endothelial cells. The expression of adhesion molecules was assessed by an ELISA method and compared with the effect of an optimal dose of human recombinant (hr) TNF. Results showed that AM supernatants, from challenged asthmatics developing an LAR, increased significantly the ICAM-1 and ELAM-l expression on endothelial cells to a level similar Io that obtained in thc presence of hrTNF (500 U/ml)(P&lt;0·001 in both cases, respectively 90·4% and 75·2% of the level obtained with hrTNF). In contrast, AM supernatants from asthmatics at baseline or exhibiting, after challenge, a single early reaction had no significant effect on these parameters (P=NS in both cases, respectively 23·5% and 24·7% of the ICAM-1 expression, 22·7% and 15·3% of the ELAM-1 expression obtained with hrTNF). AM-derived TNF present in these supernatants was thought to play a key role in endothelial cell stimulation, since: (i) TNF concentration in AM supernatants correlated with its effect on ICAM-1 (r= 0·80. P 10−4) and ELAM-1 expression (r = 0·88, P 10–5); and (ii) a neutralizing anti-TNF antibody decreased their effect (68% and 80% respectively on ICAM-1 and ELAM-1 expression). Moreover, the role of IL-6 was excluded on the basis both of the hrIL-6 inefficiency to induce ICAM-1 and ELAM-1 synthesis, even in costimulation with hrTNF, and of anti-IL-6 antibody to neutralize the effect of AM supernatants. Our results suggest that, beside mast cells and lymphocytes, macrophages might participate in the induction of the local inflammatory reaction observed in bronchial asthma. During the LAR, cytokines and especially TNF are able, through an enhanced adhesion molecule expression on endothelial cells, to facilitate the bronchial cellular influx.
T cell epitopes of the major fraction of rye grassLolium perenne (Lol pI) defined using overlapping peptidesin vitroandin vivo. I. Isoallergen clone 1A
Authors: BUNGY POOR FARD G A , LATCHMAN Y , RODDA S , GEYSEN M , ROITT I , BROSTOFF J 
Published: July 2010

SUMMARYOne hundrcd and fifteen overlapping synthetic peptides spanning the entire sequence of the isoallergen clonelA of Lol p I from rye grass Lolium perenne were synthesized by the multi-pin technique. The peptides were overlapping 12mers, offset by two residues and overlapping by 10 residues. Sets of six adjacent overlapping peptides (except pool-1,15,20) were pooled and were used in vitro and in vivo to map the T cell epilopes on Lol p I. Six atopics who were skin test and RAST positive to rye grass showed T cell responses to L. perenne extract (LPE) and its major fraction (Lol p I). Five out of six showed T cell responses in vitro to peptide pool-17, while five non-atopics did not respond to any of the peptide pools. By testing the individual peptides of pool-17, we have located the T cell epitope on Lol p I. Interestingly, when we tested pool-17 and its single peptides in vivo by intradermal skin testing we found in one patient a typical DTH after 24–48 h to pool-17 and its peptides (peptides 3 and 4) which exactly matched the in vitro responses. By defining the T cell epitopes in this way a greater understanding of the allergic response to pollen will be obtained, and a more effective and less dangerous vaccine may be possible for treating patients with hay fever.
Analysis of cytokine profiles in synovial T cell clones from chlamydial reactive arthritis patients: predominance of the Th1 subset
Authors: SIMON A K , SEIPELT E , WU P , WENZEL B , BRAUN J , SIEPER J 
Published: July 2010

SUMMARYSubpopulations of human T cells (Th0, Th1 and Th2) can be distinguished by their cytokine-sceretion pattern. Evidence is increasing from other studies that the outcome of a human disease may depend on the subpopulation of T cells that predominates at the site of inflammation. Reactive arthritis serves as a useful model of chronic inflammatory diseases, because the triggering antigen can be identified. Using this triggering antigen we raised 33 Tcell clones reactive with Chlamydia trachomatis and 25 T cell clones that were not reactive, all from the synovial fluid of two patients suffering from Ohlamydia-induced arthritis. Their cylokine secretion patterns for inlcrferon-gamma (IFN-γ), IL-2 and IL-4 were analysed, as also were mRNAs for IFN-γ and IL-10 by in situ hybridization. Out of the 33 antigen-reactive clones 23 showed a Th1 pattern with IFN-γ but not IL-4 secretion, while the remaining 10 exhibited a ThO pattern. The clones that did not react with Chlaniydia expressed all patterns of cytokine secretion, including a Th2 pattern, thus providing a control population that excludes bias in the sampling procedure. CD4 and CD8 clones displayed a similar cytokine-secretion pattern. In addition this study demonstrates for the first time the expression of IL-10 mRNA in Tcell clones derived from synovial fluid, and ihis was not confined to the Th2 subset. The Th1 response that Chlamydia provoke can be regarded as appropriate for such an obligate intracellular pathogen.
Remission of experimental autoimmune hepatitis is associated with antigen-specific and non-specific immunosuppression
Authors: LOHSE A W , MEYER zum BÜSCHENFELDE K-H 
Published: July 2010

SUMMARY
Experimental autoimmune hepatitis (EAH) is an animal model for autoimmune hepatitis. The disease is T cell-mediated and runs a subacute course, with maximal disease activity around week four after disease induction and a slow ensuing recovery. The aim of the present study was to investigate the immunoregulatory mechanisms that may account for recovery in EAH. It was found that T cell reactivity to liver antigens preceded histological disease, but at the peak of disease activity this T cell response was already suppressed. Active and antigen-specific suppression could be demonstrated, as irradiated splenocytes from animals at the beginning of recovery from EAH were able to suppress in vitro the T cell response to liver antigens by 42%. The response to an irrelevant antigen was suppressed by 16%, showing additional antigen non-specific suppression in vitro. The response to an in vivo immunization with an unrelated microbial antigen (tetanus toxoid) at the peak of disease was markedly reduced (by 90%). These data demonstrate in vitro and in vivo immunosuppression associated with the overcoming of and recovery from EAH. They stress the importance of immunoregulatory cycles in the control of autoimmune hepatitis.
Genetic analysis of the variable region genes encoding a monospecific human natural anti-DNA antibody
Authors: DALEY M D , MISENER V , OLEE T , CHEN P P , SIMINOVITCH K A 
Published: July 2010

SUMMARYRecent evidence suggests that natural autoantibodies may play an integral rote in the development of the normal immune repertoire. To explore the genetic origins of these antibodies, we have isolated and sequenced the variable (V) region genes encoding both the heavy (H) and light (L) chains of a natural anti-DNA antibody, Kim It.4. The genes appear to be derived from the VH4.t8 (subgroup VHIV), JH5, Hum ILI (subgroup VλI) and Jλ3 germline genes. The origin of the H chain diversity gene is more obscure, being potentially derived from one or more of several germline genes, arranged in either the forward or reverse orientations. Both the Kim 11.4 VH and VL genes share significant degrees of similarity with those utilized in other autoantibodies, indicating that at least some degree of V restriction may exist in human autoreactive B cells. The pattern of nucleotide differences between the Kim 11.4 VH and VL genes and their putative germline counterparts suggests that the Kim 11.4 genes may have undergone somatic mutation and arisen as a result of antigen selection.
Expression of anticardiolipin cofactor, human β2-glycoprotein I, by a recombinant baculovirus/insect cell system
Authors: IGARASHI M , MATSUURA E , IGARASHI Y , NAGAE H , MATSUURA Y , ICHIKAWA K , YASUDA T , VOELKER D R , KOIKE T 
Published: July 2010

SUMMARYA full-length cDNA coding a human β2-glycoprotein I (β2-GPI) was introduced into the baculovirus genome to construct a recombinant baculovirus. Spodoptera frugiperda (Sf9) cells were infected with the recombinant baculovirus. A protein (mol. wt 43000) reactive with anti-β2-GPI antisera was produced in the insect cells and secreted into the culture medium. The recombinant β2-GPI was purified from the culture supernatant by sequential cardiolipin (CL)-affinity column chromatography and gel filtration. The N-terminal amino acid sequence of the protein was identical to that of the native β2:-GPI purified from human sera, and a putative signal peptide was cleaved from the secreted form of the recombinant protein. The purified recombinant protein had a cofactor activity which enhances CL binding of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE) patients, as well as the native β2-GPI. Thus, the β2-GPI expressed in insect cells is an immunologically active cofactor.
Molecular mechanisms resulting in pathogenic anti-mouse erythrocyte antibodies in New Zealand black mice
Authors: SCOTT B B , SADIGH S , STOW M , MAGEED R A K , ANDREW E M , MAINI R N 
Published: July 2010

SUMMARYThe New Zealand black (NZB) mouse strain is genetically predisposed to develop, at approximately 6 months of age, a spontaneous and severe autoimmune anaemia caused by production of pathogenic anti-mouse erythrocyte autoantibodies. In order to investigate the molecular mechanisms which lead to anti-mouse erythrocyte autoantibody production we have generated eight anti-mouse erythrocyte MoAbs producing hybridomas from splenocytes of 9- and 12-month-old NZB with spontaneous autoimmune anaemia. IgG2a was the predominant isotype, while IgM, IgG1 and IgG2b were each produced by one hybridoma cell line. All anti-mouse erythrocyte MoAbs were characterized for their antigen specificities. None of the MoAbs cross-reacted with ss- or dsDNA or with other species' erythrocytes, with the exception of one MoAb which cross-reacted with rat erythrocytes. None of the eight hybridomas was demonstrated to express surface or cytoplasmic CD5, suggesting that they derived from CD5- B lymphocytes. All hybridomas when implanted intraperitoneally into BALB/c mice caused anaemia. In order to define the genetic basis and investigate the molecular mechanisms resulting in pathogenic anti-mouse erythrocyte autoantibody production, the pattern of immunoglobulin variable region gene use has been studied. Five of the eight MoAbs whose IgVH genes were sequenced all have functionally rearranged genes from the VH J558 gene family. There is evidence for somatic point mutations in the complementarity-determining regions (CDR) of the IgVH genes in all of these five MoAbs when compared with the closest known germline gene. We suggest that these nucleotide sequence changes are likely to reflect selection by an antigen-driven mechanism. Furthermore, the data indicate that pathogenic anti-mouse erythrocytes are not derived from ‘natural’ autoantibodies.
Antibody-dependent cellular cytotoxicity and neutralizing activity in sera of HIV-1-infected mothers and their children
Authors: BROLIDEN K , SIEVERS E , TOVO P A , MOSCHESE V , SCARLATTI G , BROLIDEN P A , FUNDARO C , ROSSI P 
Published: July 2010

SUMMARYThe prognostic and protective role of antibodies mediating cellular cytotoxicity (ADCC) and neutralization was evaluated in sera of HIV-1-infected mothers and their consecutively followed children. The presence and titres of ADCC mediating and/or neutralizing antibodies in maternal sera did not predict HIV-1 infection in their respective children. No significant difference in the sera from the children was seen when comparing the presence of neutralizing antibodies between the uninfected and infected children. Stratification of the infected group according to clinical status revealed differences. Only one of 24 AIDS patients had a high neutralizing titre against IIIB. Four patients had a very low titre and the remaining had no detectable neutralizing antibodies at all. In contrast, 10/17 infected non-AIDS children had neutralizing antibodies. Similarly, no significant difference was seen when comparing the presence of ADCC-mediating antibodies between the uninfected and the infected group of children. However, a significantly higher frequency of ADCC was seen in the seropositive non-AIDS children compared with the AIDS children. This study clearly shows that the presence of antibodies mediating ADCC and neutralization in infected children, 0–2 years old, is associated with a better clinical status and delayed disease progression.
Programmed cell death (apoptosis) as a mechanism of cell death in peripheral blood mononuclear cells from cats infected with feline immunodeficiency virus (FIV)
Authors: BISHOP S A , GRUFFYDD-JONES T J , HARBOUR D A , STOKES C R 
Published: July 2010

SUMMARYFIV is a lentivirus infection of cats which induces an immunodeficiency syndrome associated with curly qualitative defects in antigen-specific T cell function and with late quantitative detects in CD4+ T lymphocytes. We have observed that peripheral blood mononuclear cells (PBMC) from FIV-infected cats have impaired survival in culture. The mechanism of this in vitro dysfunction and depletion is not known. We have proposed that inappropriate induction of programmed cell death (apoptosis) could account for these in vitro defects. Here, we report that PBMC from FIV-infected eats, with impaired T cell blastogenesis and impaired survival in vitro, undergo an active cell death upon culture, which has the morphological and biochemical characteristics of programmed cell death (PCD). Apoptosis occurred in all six asymptomatic FIV-infected cats, and in none of the nine uninfected cats, which were studied. Changes in cell morphology under both light and electron microscopy, and fragmentation of genomic DNA were characteristic for apoptosing cells. Cell death was spontaneous and occurred in the absence of any stimuli, and culture with the T cell mitogen, concanavalin A (Con A), did not significantly enhance cell death. Activation-induced cell death was inhibited, in a dose-dependent, manner, by addition to the incubation medium of zinc, which has been shown to inhibit the action of endonuclease responsible for the characteristic fragmentation of DNA. Since apoptosis has recently been implicated in AIDS pathogenesis, FIV infection may prove useful to study this aspect of retroviral, in particular HIV, infection.
Comparative effects ofMycobacterium aviumglycopeptidolipid and lipopeptide fragment on the function and ultrastructure of mononuclear cells
Authors: POURSHAFIE M , AYUB Q , BARROW W W 
Published: July 2010

SUMMARYAmong the various lipids associated with the cell envelope of the Mycobacterium avium complex, the species-specific glycopeptidolipids (GPL) are responsible for distinguishing one serovar from another. In a continuing effort to study the immunonodulatory capabilities of these mycobacterial lipids, we have examined and compared the effects of the GPL and its lipopeptide fragment (β-lipid) on mononuclear cell function. It was observed that the lymphoproliferative response of murine splenic mononuclear cells to mitogen stimulation was reduced by both the GPL and its lipopeptide fragment. Although the responsiveness appeared to be down-regulated to a greater degree by the β-lipid, treatment with either GPL or β-lipid resulted in the release of soluble factors from peritoneal macrophages that caused suppression of the lymphoproliferative responsiveness of splenic mononuclear cells. Flow cytometric analysis of peritoneal macrophages revealed that treatment with the β-lipid fragment caused a marked decrease in expression of the C3bi complement receptor. Mac-1, on macrophages, whereas treatment with GPL resulted in a marked increase in the expression of Mac-2 receptor on macrophages. Treatment of peritoneal macrophages with either GPL or β-lipid resulted in the release of tumour necrosis factor (TNF), as determined by an 1929 biological cytotoxicity assay. Perturbation of macrophage membrane ultrastructure by both GPL and β-lipid was confirmed by electron microscopy, and may be a possible explanation for the resulting alterations in mononuclear cell function observed in this study.
Metabolic fate of monovalent and multivalent antibodies of Heymann nephritis following formation of surface immune complexes on glomerular epithelial cells
Authors: SINGH A K , KASINATH B S 
Published: July 2010

SUMMARYHeymann nephritis of the rat has several similarities to human idiopathic membranous glomerulonephropathy, and therefore serves as an animal model for study of the human disease. The disease process in the rat is initiated by autoantibodies forming in situ immune deposits on the surface of the glomerular epithelial cell in the lamina rara externa region of the glomerular basement membrane. It is now understood that multispecific antibodies (like anti-gp600) form the nephritogenic deposits which cause proteinuria, while MoAb (like anti-gp300, anti-90 kD and anti-gp70) form only transient deposits which do not give rise 10 proteinuria. The reasons for differences between pathologic effects of mono- and multispecific antibodies are not known. Following characterization of putative antigens of Heymann nephritis by immunofluorescence, immunogold and immunoblot techniques, we have investigated the metabolic handling of a multispecific (anti-600), monospecific antibody (anti-gp70) and a MoAb (anti-gp330) by the cultured glomerular epithelial cell to gain an insight into the mechanism of nephritogenicity of multispecific antibody. Anti-gp600 reacted to multiple antigens in the 330-kD and 70-kD regions; anti-gp70 reacted to only the 70-kD region. Ultrastructurally, all three types of antigens were present on the plasma membrane, concentrated in the microvillar region. The cells were incubated with the antibodies, and clearance of the antibodies from the cells was evaluated. Following binding, all three antibodies were internalized by the cells. However, it was found that monoclonal anti-gp330 MoAb was cleared most rapidly from the cell (t1/2: 5 min), followed by anti-gp70 (t1/2; 30 min). Anti-gp600 was cleared at four times slower rate than anti-gp70(t1/2 2 h) by the cell. While anti-gp330 MoAb and monospecific anti-gp70 antibody were expelled from the cell in 25–32% digested form, the multispecific anti-gp600 was digested to the extent of only 5–8%. No immune complexes were detected in the medium with any of the three antibodies. The shed label was in intact IgG form. It is concluded that multispecific antibodies of Heymann nephritis are nephritogenic because of their slower clearance and digestion and therefore, higher accretion rate on the surface of the glomerular epithelial cell The differential handling of the antibodies by the glomerular epithelial cell offers an explanation for the in vivo differences in the nephritogenicity of these antibodies observed earlier.