bluuebunny/crossref_metadata_2025_split huggingface dataset:
Production of erythrocyte autoantibodies in NZB mice is inhibited by CD4 antibodies
Authors: OLIVEIRA G G S , HUTCHINGS P R , ROITT I M , LYDYARD P M 
Published: July 2010

SUMMARYNZB mice spontaneously develop haemolytic anaemia as the result of production of erythrocyte autoantibodies. The mechanisms leading to breakdown in tolerance to erythrocyte autoantigens are unknown. Antibodies to CD4 have been successfully used to treat several murine models of autoimmune disease. In this study we injected NZB mice with non-depleting CD4 antibodies and were able to prevent and abrogate erythrocyte autoantibody production in young (Coombs'negative) and old (Coombs'positive) mice, respectively. Our data indicate the dependency of autoantibody production on CD4+T cells. However, withdrawal of anti-CD4 antibodies resulted in the appearance of erythrocyte autoantibodies, showing that under these conditions we were unable to re-establish tolerance to autoantigens on erythrocytes using anti-CD4 treatment.
A major pathogenic antigen of Heymann nephritis is present exclusively in the renal proximal tubule brush border—studies with a monoclonal antibody against pronase-digested tubular antigen
Authors: TSUKADA Y , ONO K , MAEZAWA A , YANO S , NARUSE T 
Published: July 2010

SUMMARYWe have isolated a nephritogenic 120-kD antigen from rat renal tubule brush border that induces rat Heymann nephritis. A MoAb that recognized this antigen reacted exclusively with the brush border on indirect immunofluorescence and immunoelectron microscopy. Rabbit antiserum against this antigen also reacted exclusively with the brush border. With the injection of this antiserum, rabbit IgG became detectable along the glomerular basement membrane (GBM) after 3 days. Our 120-kD antigen was shown to have a close relationship with gp330 based on the following: (i) this antigen can induce active Heymann nephritis as gp330: (ii) our MoAb reacted with the immune deposits of nephritic kidneys induced not only by the 120-kD antigen but also by gp330, and conversely, rabbit antiserum against gp330 reacted with those induced by the 120-kD antigen as well as gp330; and (iii) by immunoblotting, polyclonal antibodies against the 120-kD antigen reacted with gp330 and polyclonal antibodies against gp330 reacted with the 120-kD antigen. These observations indicate that antigen present exclusively in the brush border can induce active Heymann nephritis, and the common antigenic determinants shared by brush border and the coated pits of glomerular epithelium may not be a prerequisite to induce nephritis. A more precise relationship between the 120-kD antigen and reported C14 fusion protein or 40-kD α2MRAP remains to be established.
A high percentage of HLA-DQ+ and HLA-DR+ mononuclear cells is associated with a low incidence of acute graft-versus-host disease after allogeneic bone marrow transplantation (BMT) in children
Authors: GARIN L , RIGAL D , EL MARSAFY S , BERNAUD J , PHILIPPE N , SOUILLET G 
Published: July 2010

SUMMARYIn order to discover some biological markers of acute graft-versus-host disease (aGVHD), we have studied the percentage of peripheral monocytes and T lymphocytes bearing HLA-DR and HLA-DQ class II molecules. This study included 25 aliogeneic BMT in children, cither with (n= 10) or without (n= 15) aGVHD. Within 2 months after transplantation, a higher percentage of DQ+ and DR+ monocytes and of DQ+ T lymphocytes was observed in patients without aGVHD compared with patients with aGVHD. The most discriminating marker was the strong increase in the percentage of DO+ monocytes in patients without aGVHD (P= 0·001). In a sequential study, we observed a low percentage of DQ+ and DR+ peripheral blood mononuclear cells (PBMC) as long as the clinical manifestations of aGVHD continued. We speculate if the modulation of DQ and DR molecules on PBMC after BMT is a consequence of the action of some lymphokines, and if it plays a role in the regulation of the acute GVH reaction. We conclude that MHC class II molecules on peripheral mononuclear cells may be reliable biological markers for the diagnosis of aGVHD.
Intraperitoneal immunization of human subjects with tetanus toxoid induces specific antibody-secreting cells in the peritoneal cavity and in the circulation, but fails to elicit a secretory IgA response
Authors: LUE C , VAN DEN WALL BAKE A W L , PRINCE S J , JULIAN B A , TSENG M-L , RADL J , ELSON C O , MESTECKY J 
Published: July 2010

SUMMARYFive patients on continuous ambulatory peritoneal dialysis (CAPD) were immunized intraperitoneally with tetanus toxoid (TT) through an indwelling catheter. Four control patients on CAPD received the same dose of TT intramuscularly. Before immunization, virtually no anti-TT antibody-secreting cells (AbSC) were detected by the enzyme-linked immunospot (ELISPOT) assay in peripheral blood or peritoneal fluid from patients of either group. One to 2 weeks after immunization, high frequencies of TT-specific AbSC were detected in the circulation and peritoneal cavity. More than 80% of those cells were of the IgG isotype, with IgA accounting for most of the remainder. Patients receiving TT by the i.p. route showed significantly higher frequencies of specific IgG and IgA AbSC in the peritoneal cavity than patients immunized intramuscularly. Frequencies of AbSC in peripheral blood did not significantly differ between the two groups. Immunization with TT by both routes resulted in a significant increase of IgG anti-TT antibodies in serum, saliva and peritoneal fluid. A significant IgA antibody response was seen only in serum and peritoneal effluents. Therefore, i.p. immunization of human subjects with TT elicited both a localized response in the peritoneal cavity as well as a systemic response in serum, but did not induce a salivary IgA response.
The human T cell antigen receptor repertoire: skewed use of Vβ gene families by CD8+ cells
Authors: CLARKE G R , HUMPHREY C A , LANCASTER F C , BOYLSTON A W 
Published: July 2010

SUMMARYThe TCR repertoire of human CD8+ peripheral blood lymphocytes has been determined using MoAbs to the Vβ2, 3,5.1,5.2/5.3,6.7,8,12 and 19(17) Vβ gene families. The CD8 T cell repertoire for Vβ2 and Vβ3 is shown to be skewed, with an excess of individuals having higher values than are consistent with a normal distribution. A significant majority of these individuals are over the age of 40. High values of Vβ CD8+ cells were found for each Vβ family studied except for 6.7a. Individual high values are stable for at least 12 months. In addition, the total percentage of CD4 and CD8 cells reacting with this panel of reagents was determined. There is a significant excess of Vβ+ CD4+ cells (33%) over CD8+Vβ+ cells (21·9%). Thus the human CD8 Vβ repertoire differs from the human CD4 repertoire in a number of important ways.
Characterization of the increased cytotoxicity of gelonin anti-T cell immunoconjugates compared with ricin A chain immunoconjugates
Authors: FISHWILD D M , WU H-M , CARROLL S F , BERNHARD S L 
Published: July 2010

SUMMARYRibosomal inactivating proteins such as gelonin (Gel) and ricin A chain (RTA) conjugated to MoAbs bind to specific target cells, and upon internalization inhibit protein synthesis, ultimately resulting in cell death. We report here that Gel anti-T cell MoAb conjugates are more cytotoxic than RTA conjugates when tested against human peripheral blood mononuclear cells (PBMC). This increased cytotoxicity is observed whether Gel is conjugated to the anti-T cell MoAb or to an anti-mouse immunoglobulin Fab′ fragment which then binds to the murine anti-human T cell MoAb. Gel conjugates are not only effective at lower concentrations, but also produce a greater extent of inhibition of cellular proliferation. Moreover, a 10 min exposure to a Gel conjugate is as effective as a 90 h exposure to an RTA conjugate. When part of anti-T cell F(ab′)2 or Fab′ conjugates, Gel affects the early steps in cellular intoxication more than RTA, Gel conjugates bind more avidly and accelerate the modulation of antigen. In contrast, when part of whole IgG conjugates, Gel does not affect the binding to or modulation of surface antigen compared with RTA, while it does increase conjugate cytotoxicity. These observations suggest that Gel may be delivered more efficiently into the cytosol than RTA. A divergent intracellular pathway for Gel is also supported by the inability of chemical potentiators, which strongly enhance RTA potency, to affect Gel potency. These properties of Gel might also be advantageous for targeted immunoconjugates made with other MoAbs or receptor-binding molecules.
Pathogenic anti-DNA idiotype-reactive IgG in intravenous immunoglobulin preparations
Authors: SILVESTRIS F , CAFFORIO P , DAMMACCO F 
Published: July 2010

SUMMARYThis study was addressed to explore the reactivity of natural anti-idiotypes from commercial lots of immunoglobulins to several idiotypes (Ids), usually expressed by anti-DNA molecules in lupus nephritis. Eleven intravenous immunoglobulin (IVIG) preparations and nine (three polyvalent and six hyper-immune) intramuscular IgG were Investigated for specific content of anti-DNA, anti-F(ab′)2 and antibodies reacting with several anti-DNA IgG Ids. Two samples (nos 6 and 11) showed high reactivity with allogeneic F(ab′)2 and with F(ab′)2 of myeloma proteins bearing the anti-DNA Id 31+ and the 8.12+. Since both 31 and 8.12 Id markers are known to characterize pathogenic anti-DNA IgG in systemic lupus erythematosus (SLE), anti-Id antibodies to these markers were obtained by absorbing the IVIG samples nos 6 and 11 to Sepharose columns coupled with pooled (ab′)2 fragments of 31+-F4+-8.12+-myeloma proteins. Inhibition experiments showed that anti-8.12 Id-eluted IgG induced a selective suppression of the DNA-reactive antibodies derived from patients with active lupus nephritis to their substrate, suggesting the involvement of 8.12+ molecules in the SLE glomerular damage. Since 8.12+ anti-DNA are nephritogenic antibodies, the occurrence of anti-8.12+ Id in commercial IVIG may be of potential therapeutic relevance in modulating the pathogenic SLE Id network. Previous variable results of IVIG treatment in SLE, such as resolution of proteinuria or worsening nephritis, could be related to variable enrichment of different lots of IVIG in suppressive anti-pathogenic Id antibodies.
The role of tumour necrosis factor-alpha and IL-1 in polymorphonuclear leucocyte and T lymphocyte recruitment to joint inflammation in adjuvant arthritis
Authors: ISSEKUTZ A C , MEAGER A , OTTERNESS I , ISSEKUTZ T B 
Published: July 2010

SUMMARYThe mediators involved in leucocyte recruitment to joints during arthritis are not fully defined, but two important proinflammatory cytokines, IL-1 and tumour necrosis factor-alpha (TNF-α), are produced in joints in rheumatoid arthritis (RA). We investigated in the rat adjuvant arthritis model whether endogenous IL-1 and TNF-α contribute to joint inflammation and polymorphonuclear leucocyte (PMNL) and T lymphocyte infiltration. The migration of51 Cr-labelled rat blood PMNL and 111In-labelled T lymphocytes to the joints of rats with adjuvant arthritis was measured along with plasma protein extravasation, which was quantified using 125I-labelled human albumin. Rats with active arthritis of 5 days' duration received i.p. non-immune serum, polyclonal neutralizing anti-serum to rat TNF-α, antiserum to IL-α and IL-β or both anti-TNF plus anti-IL-l for 5 days. Treatment with anti-IL-1α and IL-1β did not affect plasma protein extravasation, or PMNL or T lymphocyte accumulation in the joints (i.e. talar joint, hind paws, and tail) despite the fact that this treatment inhibited 80–90% of the PMNL migration into dermal sites injected with IL-1α or IL-1β In contrast, anti-TNF-β treatment significantly improved clinical scores, decreased plasma protein extravasation by 60–80%, inhibited PMNL accumulation by 40–50% and decreased T lymphocyte accumulation by 30–50%. Treatment with anti-IL-1, together with anti-TNF-α, significantly potentiated the inhibition of T lymphocyte accumulation observed with anti-TNF-α alone. These results indicate that endogenous TNF-α production may play an important role in the inflammatory changes and leucocyte recruitment in this experimental model of human arthritis, while IL-1 may have a less important role in leucocyte recruitment to these joints.
Cytotoxic T lymphocyte activity and CD8 subpopulations in children at risk of HIV infection
Authors: ALDHOUS M C , WATRET K C , MOK J Y Q , BIRD A G , FROEBEL K S 
Published: July 2010

SUMMARYHIV-specific cytotoxic T lymphocytes (CTL) are thought to play a major role in viral control in HIV-infected adults. Changes in the relative proportions of CD8 lymphocyte subpopulations are also thought to be associated with disease progression. Less is known about the relative effectiveness of CTL against different HIV targets, or about the relationship, if any, between CTL activity and CD8 subpopulations. We have measured CTL activity against four HIV gene products (gag, tat, pol and env) and expression of CD45RO, CD45RA, HLA-DR, CD29, S6F1, and CD57 surface markers on CD8 cells from nine HIV-infected and 11 HIV-uninfected children. Of nine HIV-infected children, six showed antigen-specific CTL activity on at least one occasion: 4/6 directed against tat, 6/6 against pol, 1/6 against env, and 1/6 against gag. However, the specificity of the CTL activity varied between children and within individual children with time. Furthermore, two uninfected children showed CTL activity, one to HIV-gag,-pol and -tat, and the other to HW-pol. All the HIV-infected and two uninfected children had abnormal proportions of CD8 subpopulations in whole blood compared with age-matched controls. There was no correlation between CTL activity and CD8 subsets in whole blood. Five children changed from CTL-positive to CTL-negative (or vice versa) during the study. In these, the occasions when CTL activity was detected coincided with an increase in CD8 cells, an expansion of HLA-DR+ CD8 cells and a loss of CD45RA+ CD8 cells.
Mycobacterium aviuminfection in HIV-1-infected subjects increases monokine secretion and is associated with enhanced viral load and diminished immune response to viral antigens
Authors: DENIS M , GHADIRIAN E 
Published: July 2010

SUMMARYThe complex interaction between HIV-1 infection and Mycobacterium avium was studied. Viral burden was assessed, as well as immune response to HIV-1 in the context of Myco. avium infections. We also examined serum cytokine levels and cytokine release by blood mononuclear cells in HIV-1-infected subjects, infected or not with Myco. avium. Undetectable serum levels of IL-1, tumour necrosis factor-alpha(TNF-α) and IL-6 were found in normal controls and in groups I, II and III of HIV-1-infecled subjects. Moderate levels of TNF-α, IL-1 and IL-6 were found in the sera of group IV patients. When group IV was subdivided into subjects with and without Myco. avium infections, subjects with Myco. avium infections were shown to have higher serum levels of TNF-α, IL-Iβ and IL-6 than those with other infections. Blood mononuclear cells from controls and HIV subjects were stimulated with bacterial lipopolysaccharide, and cytokine levels assessed. Cells from group II patients were shown to secrete normal levels of TNF-α and IL-6, and lower levels of IL-1β group III subjects released higher levels of IL-6. Patients in group IV had blood cells that released elevated levels of lL-6 and TNF-α, and lower levels of IL-β Group IV subjects with Myco. avium infections had blood cells that released higher levels of TNF-α, IL-6 and IL-1 than group IV subjects with other infections. Assessment of viral burden in cells of HIV-1-infected subjects revealed that Myco. avium-infected subjects had a higher level of virus burden and a lower level of lymphoproliferative response to an inactivated gp120-depleted HIV-1 antigen than AIDS subjects with other infections. These data suggest that Myco. avium infections in HIV-1-infected subjects hasten the progression of viral disease, enhance cytokine release and contribute to the anergy to viral antigens.
Differences in immune recognition of cytochrome P4502D6 by liver kidney microsomal (LKM) antibody in autoimmune hepatitis and chronic hepatitis C virus infection
Authors: MA Y , PEAKMAN M , LOBO-YEO A , WEN L , LENZI M , GÄKEN J , FARZANEH F , MIELI-VERGANI G , BIANCHI F B , VERGANI D 
Published: July 2010

SUMMARY
LKM-1 antibody, which characterizes a subtype of autoimmune hepatitis (AIH), is also found in some patients with chronic hepatitis C virus (HCV) infection. It has been suggested that HCV initiates autoimmunity through molecular mimicry, because there is partial identity between HCV and cytochrome P4502D6 (CYP2D6), the putative target of LKM-1. Whether CYP2D6 is the target of LKM-1 in HCV-related liver disease, however, is controversial. To clarify this issue, we have studied by phage plaque assay and Western blot the reactivity to recombinant CYP2D6, isolated from a human liver cDNA library, in 55 patients with LKM-1, 18 (14 females, median age 12 years) anti-HCV-negative, with classical AIH, and 37 (27 females, median age 52 years) anti-HCV-positive. Reactivity to CYP2D6 was found in 72% of the anti-HCV-negative, but only in 27% of the anti-HCV-positive patients (P &lt; 0.001), although immunofluorescence LKM-1 titres were similar in the two groups. In addition, to investigate whether the antibody responsible for the LKM-1 fluorescent pattern also reacts with CYP2D6, we have determined the specificity of LKM-1 antibodies present in the supernatant of lymphoblastoid B cell lines obtained from two patients with LKM-1-positive AIH. An oligo/monoclonal antibody thus generated gave both the typical fluorescent pattern and reacted with CYP2D6. Our results show that whilst antibodies producing the characteristic LKM-1 fluorescent pattern can react with CYP2D6, not all LKM-1-positive sera do so, particularly if obtained from patients with chronic HCV infection. This suggests that LKM-1 in HCV infection recognizes epitopes or antigens different from those targeted in AIH.
Altered expression of CD11/CD18 on the peripheral blood phagocytes of patients with tuberculosis
Authors: YASSIN R J , HAMBLIN A S 
Published: July 2010

SUMMARYTuberculosis (TB), caused by Mycobacterium tuberculosis, is characterized by granulomatous lesions made up of epithelioid cells, giant cells and mononuclear leucocytes. Cell-cell adhesion is important in granuloma formation and in the leucocyte migration which accompanies it. We have recently shown increased expression of the adhesion molecules CD11/CD18 (Leu CAMs, β2 integrins) on peripheral blood leucocytes from patients with sarcoidosis (Shakoor & Hamblin, 1992). Here we have studied the expression of CD11/CD18 and CD29 (VLA β1 integrin) on the peripheral blood leucocytes of 10 TB patients by flow cytometry. The density (expressed as mean fluorescence intensity) of CD11b on monocytes and polymorphs was increased (P &lt; 0·005) as was CD11c (P&lt; 0·005) and CD18 (P &lt; 0·05) on polymorphs. CD1la expression was significantly reduced on polymorphs (P &lt; 0·05). No differences were found in the expression of CD29, the percentages of cells expressing any molecule and, in contrast to sarcoidosis, the density of any molecule on lymphocytes. Although the cytokine tumour necrosis factor (TNF) has been implicated in the process of up-regulation, an ELISA for TNF failed to detect significant levels in plasma. The results suggest increased peripheral phagocyte CD11/CD18 expression is a feature of TB, which may contribute to the pathological processes involved.
Humoral and cellular immune recognition of Helicobacter pylori proteins are not concordant
Authors: SHARMA S A , MILLER G G , PEREZ-PEREZ G I , GUPTA R S , BLASER M J 
Published: July 2010

SUMMARY
Helicobacter pylori is a major cause of chronic antral gastritis and peptic ulcer disease. Further definition is needed of the factors that determine whether infected individuals remain asymptomatic, or ultimately develop ulceration of the mucosa or transformation to malignancy. To explore the possibility that host response to H. pylori may play a role in the outcome of this infection. we have examined humoral and cellular recognition of several H. pylori proteins by seropositive and seronegative persons. A complex mixture of water-extractable cell proteins, which did not include lipopolysaccharide (LPS), was recognized by serum antibodies only in seropositive or infected individuals. IgG from seropositive subjects also bound to urease and to a heat shock protein (hsp)60 that is homologous to the 65-kD mycobacterial heat shock protein, while sera from uninfected individuals were negative. Although antibody responses to these antigens were restricted to seropositive subjects, T cell recognition of the same proteins was found in both seropositive and seronegative subjects. The water extract of H. pylori stimulated peripheral blood mononuclear cells (PBMC) from all subjects, while purified proteins activated lymphocytes of only some seropositive and seronegative subjects. PBMC that were activated by the H. pylori hsp60 did not respond to the autologous human p60 heat shock protein. These results demonstrate that, in contrast to antibody responses, T cell recognition of H. pylori proteins may occur in non-infected persons. In addition, the data suggest that in these subjects, peripheral lymphocytes that are activated by bacterial heat shock proteins do not mediate tissue damage by recognition of human heat shock homologues.
Characterization of anti-peptide antibodies directed against an extracellular immunogenic epitope on the human α1-adrenergic receptor
Authors: FU M L X , WALLUKAT G , HJALMARSON A , HOEBEKE J 
Published: July 2010

SUMMARY
A synthetic peptide corresponding to amino acids 192–218 of the second extracellular loop of the human αIA-adrenergic receptor was used to raise antibodies in rabbits, Affinity-purified antibodies specifically recognized main bands with a molecular weight of about 68, 40 and 37 kD on the electrotransferred membrane proteins of rat ventricle membranes. The incubation of these antibodies with rat myocardial membranes resulted in a decrease in the number of binding sites for the specific radiolabelled α1-antagonist prazosin. These antibodies were also able to mimic the effects of agonist stimulation as demonstrated by a positive chronotropic effect on cultured cardiomyocytes. These results constitute the first immunochemical evidence of the presence of both the A and B subtypes of the α1-adrenergic receptor in the heart. They also confirm that the second extracellular loop of the α1-adrenergic receptors is an immunologically and functionally important domain.