bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of macrophage migration inhibitory factor (MIF) in murine antigen-induced arthritis: interaction with glucocorticoids
Authors: Santos L , Hall P , Metz C , Bucala R , Morand E F 
Published: March 2003

SUMMARY(MIF) is a broad-spectrum proinflammatory cytokine implicated in human rheumatoid arthritis. The synthesis of MIF by synovial cells is stimulated by glucocorticoids, and previous studies suggest that MIF antagonizes the anti-inflammatory effects of glucocorticoids. This has not been established in a model of arthritis. We wished to test the hypothesis that MIF can act to reverse the anti-inflammatory effects of glucocorticoids in murine antigen-induced arthritis (AIA). Cutaneous DTH reactions and AIA were induced by intradermal injection and intra-articular injection, respectively, of methylated bovine serum albumin in presensitized mice. Animals were treated with anti-MIF MoAbs, recombinant MIF, and/or dexamethasone (DEX). Skin thickness of DTH reactions was measured with callipers and arthritis severity was measured by blinded quantitative histological assessment of synovial cellularity. Cutaneous DTH to the disease-initiating antigen was significantly inhibited by anti-MIF MoAb treatment (P &lt; 0·001). AIA was also significantly inhibited by anti-MIF MoAb (P &lt; 0·02). DEX treatment induced a dose-dependent inhibition of AIA, which was significant at 0·2 mg/kg (P &lt; 0·05). MIF treatment reversed the effect of therapeutic DEX on AIA (P &lt; 0·001). DEX also significantly inhibited DTH reactions (P &lt; 0·05) but rMIF had no effect on this effect of DEX. DTH and AIA are MIF-dependent models of inflammation and arthritis. The reversal of glucocorticoid suppression of AIA by MIF supports the concept that MIF is a counter-regulator of glucocorticoid control of synovial inflammation. Although DTH was observed to be MIF-dependent and glucocorticoid-sensitive, rMIF had no reversing effect on the suppression of DTH by glucocorticoids. This suggests that inflammatory processes in specific tissues may respond differently to MIF in the presence of glucocorticoids.
Epitope focus, clonal composition and Th1 phenotype of the human CD4 response to the secretory mycobacterial antigen Ag85
Authors: Valle M T , Megiovanni A M , Merlo A , Li Pira G , Bottone L , Angelini G , Bracci L , Lozzi L , Huygen K , Manca F 
Published: March 2003

SUMMARYLymphoproliferation of healthy donors was tested against mycobacterial antigens (PPD, Ag85, Ag85 peptides). All PPD responders recognized the secretory antigen Ag85 and the peptide specificity for Ag85B was defined. Peptide 91–108 was recognized by 85% of donors. In addition, all CD4 T cell lines generated from 12 donors against PPD or Ag85 responded to 91–108. When this peptide was used to generate T cell lines, the cells responded also to tuberculins from atypical mycobacterial species. Thus the cross-reactive peptide behaved as quasi-universal. The analysis of TCR-BV gene usage by cell lines showed that most Ag85-specific T cells correspond to 91–108-specific clonotypes. Intracytoplasmic staining of cell lines after phorbol myristate acetate stimulation resulted in dominance of interferon-gamma (IFN-γ)-IL-4 double-positive cells, whereas antigen stimulation resulted in production of IFN-γ only. The data show that peptide 91–108 is the major focus of the CD4 response to mycobacterial antigens in peripheral blood mononuclear cells and in T cell lines from PPD responders.
Age-related autoantibody production in a nonhuman primate model
Authors: Attanasio R , Brasky K M , Robbins S H , Jayashankar L , Nash R J , Butler T M 
Published: March 2003

SummaryAutoantibody production increases with ageing. However, the pathological significance of this increase as well as the corresponding underlying mechanisms are poorly understood. To further our understanding of the role that ageing plays in the development of autoantibody responses, we used a novel nonhuman primate model consisting of healthy baboons of ages representing the entire lifespan of this animal species. Results from this study indicate that production of antinuclear antibodies, anticell extract antibodies and natural autoantibodies gradually and significantly increases from young age to old age without a corresponding increase in neither serum immunoglobulin concentration nor in levels of selected markers of immune dysregulation (sTNF-RI, sTNF-RII, IL-2 sRα and IFN-γ). Therefore, in the baboon model, autoantibodies may be produced in absence of recognizable pathological conditions of the ageing immune system.
Reduced HIV-stimulated T-helper cell reactivity in cord blood with short-course antiretroviral treatment for prevention of maternal–infant transmission
Authors: Kuhn L , Meddows-Taylor S , Gray G , Trabattoni D , Clerici M , Shearer G M , Tiemessen C 
Published: March 2003

SummaryT-helper cell responses to HIV have been associated with protection against maternal-infant HIV transmission in the absence of antiretroviral treatment, but the effects of antiretroviral treatment, now widely used for prevention, on development of these cell-mediated responses is unknown. We tested whether development of T-helper cell responses to HIV and other antigens would be affected by exposure to short-course regimens of zidovudine-lamivudine (ZDV-3TC) given to prevent maternal-infant HIV transmission. Cord blood samples were collected from 41 infants of HIV-infected mothers enrolled in a clinical trial in which they were treated with regimens of ZDV-3TC and from 29 infants whose HIV-infected mothers were not treated with any antiretroviral drugs. T-helper cell reactivity to HIV envelope peptides and other antigens was measured in vitro using a sensitive culture supernatant titration assay based on IL-2-dependent proliferation. Infants in the clinical trial were followed to 18 months to determine their HIV infection status, and venous blood samples were re-tested at 4·5 and 9 months for T-cell reactivity to HIV. HIV-stimulated T-helper cell reactivity in cord blood was detected 10-fold less frequently among those exposed to antiretroviral prophylaxis (2·4%) than among those unexposed (24·1%) (P = 0·007). Reductions in HIV-stimulated responses in cord blood occurred despite detectable HIV RNA (mean 3·38 standard deviation 0·76 log10 copies per ml) at delivery among treated women and occurred independent of treatment duration. Our results suggest that short-course antiretroviral treatment given to prevent maternal-infant HIV transmission may attenuate HIV-stimulated T-cell memory responses in the neonate.
Differential requirements for induction of total immunoglobulin and physiological rheumatoid factor production by human peripheral blood B cells
Authors: Van esch W J E , Reparon-Schuijt C C , Levarht E W N , Van kooten C , BreedveLd F C , Verweij C L 
Published: March 2003

SummaryRheumatoid factors (RFs) are autoantibodies directed against the Fc part of IgG. Considerable evidence exists that there are two classes of RFs, pathological and physiological. Whereas pathological RFs are associated with disease, physiological RFs are considered to be a normal component of the immune response. RF+ precursor B cells present as part of the B cell repertoire of healthy individuals are held responsible for the production of physiological RFs, which is a transient phenomenon with a clear correlation with an initiating stimulus such as immunization or exposure to an infection. Here we demonstrate a difference in the regulatory control of total Ig and RF production by peripheral blood (PB) B cells of both healthy controls (HC) and patients with rheumatoid arthritis (RA). Highly purified B cells from HC and patients with RA were cocultured with T cells stimulated with immobilized anti-CD3 mAb. Similar to IgM production, IgM-RF production was shown to be dependent on CD40 cross-linking. However, activation of PB B cells in the CD40 system in the presence of IL-2, IL-4, IL-10, combinations of these cytokines or supernatant of anti-CD3-stimulated T cells failed to induce detectable IgM-RF, whereas total IgM production was considerable. From these results we conclude that conditions to activate physiological RF+ B cells require additional contact besides CD40–CD40L interactions between T and B cells. Since the requirements for RF production were similar using PB B cells from HC and patients with RA it is suggested that the regulatory properties of RF+ precursors in the PB B cell compartment is equal among these groups. Together, these results indicate that conditions for the induction of total Ig and physiological RFs are different.
Determination of the frequency of HLA antibody secreting B-lymphocytes in alloantigen sensitized individuals
Authors: Mulder A , Kardol M J , Kamp J , Uit Het Broek C , Schreuder G M T , Doxiadis I I N , Claas F H J 
Published: March 2003

SUMMARYSera from prospective transplant patients are usually screened for HLA antibodies prior to transplantation, but presently available tests do not permit quantification of the humoral alloantigen directed response. We adapted a culture system for isolated human B-lymphocytes to assay the secretion of HLA-antibodies on a single cell basis. B-cell supernatants were screened for HLA antibodies by complement dependent cytotoxicity. The assay assigns precursor frequencies for HLA-alloantibody secreting B-lymphocytes (BCPFs), and simultaneously allows for dissection of the humoral alloantigen directed response into its monoclonal components. The lymphocytes of 15 HLA-seropositive multiparous women that were used to validate the assay, were found to contain HLA-BCPFs ranging from 0 to 123 per 106 B-lymphocytes (mean: 43 ± 45 per 106 B-lymphocytes). The HLA-specificities of antibodies in the B-cell supernatants were in agreement with serum specificities. Genuine HLA reactivity of B-cell supernatants was confirmed using an ELISA with purified HLA class I antigens. When applied to lymphocytes of patients on transplant waiting lists, the present assay may enable the unraveling of serum specificities in their components, thus supplementing HLA antibody serum screening data.
Intravenous immunoglobulin prevents experimental autoimmune myositis in SJL mice by reducing anti-myosin antibody and by blocking complement deposition
Authors: Wada J , Shintani N , Kikutani K , Nakae T , Yamauchi T , Takechi K 
Published: March 2003

SUMMARY
High-dose intravenous immunoglobulin (IVIG) therapy has been effective in many autoimmune and systemic inflammatory diseases including polymyositis (PM) and dermatomyositis (DM). In the present study we evaluated the efficacy of IVIG using experimental models of PM and DM. An experimental autoimmune myositis (EAM) model was produced in SJL/J mice by an immunization with rabbit myosin B (MB) fraction. In this model, the plasma level of anti-MB antibody was elevated, and mouse IgG and complement C3 were deposited in the muscle fibres. Administration of IVIG dose-dependently reduced the incidences of necrotic and inflammatory changes in the skeletal muscle. IVIG treatment also decreased the elevation of anti-MB antibody level, as well as the deposition of IgG and C3. We next evaluated the effect of IVIG in adoptive EAM mice made by an intravenous injection of lymph node cells previously stimulated with MB. Adoptive EAM mice showed similar lesions in skeletal muscle as EAM mice and IVIG inhibited the lesion development. In vitro experiments demonstrated that IVIG inhibited complement-mediated lysis of human erythrocytes sensitized with anti-human erythrocyte antibodies. The binding of C1q, C4 and C3 to the same cells was also inhibited by IVIG. Taken together these findings suggest that IVIG prevents the development of myositis in EAM and adoptive EAM models by several mechanisms, such as reducing anti-myosin antibody and by blocking complement activation. Our present findings might account for the clinical efficacy of IVIG in PM and DM patients.
Anti-galectin-1 autoantibodies in humanTrypanosoma cruziinfection: differential expression of thisβ-galactoside-binding protein in cardiac Chagas' disease
Authors: Giordanengo L , Gea S , Barbieri G , Rabinovich G A 
Published: March 2003

SUMMARYThe pathogenesis of Chagas' disease has been subject of active research and still remains to be ascertained. Galectin-1 (Gal-1), a member of a conserved family of animal β-galactoside-binding proteins, localized in human heart tissue, has been suggested to play key roles in immunological and inflammatory processes. In the present study we demonstrated the occurrence of anti-Gal-1 autoAb in sera from patients in the acute and chronic stages of Chagas' disease (ACD and CCD) by means of ELISA and Western blot analysis. We found a marked increase in the level and frequency of Ig E anti-Gal-1 antibodies in sera from patients with ACD, but a low frequency of Ig M anti-Gal-1 immunoreactivity. Moreover, Ig G immunoreactivity to this β-galactoside-binding protein was found to be correlated with the severity of cardiac damage in CCD, but was absent in nonrelated cardiomyopathies. We could not detect immunoreactivity with Trypanosoma cruzi antigens using a polyclonal antibody raised to human Gal-1 and no hemagglutinating activity could be specifically eluted from a lactosyl-agarose matrix from parasite lysates. Moreover, despite sequence homology between Gal-1 and shed acute phase antigen (SAPA) of T. cruzi, anti-Gal-1 antibodies eluted from human sera failed to cross-react with SAPA. In an attempt to explore whether Gal-1 immunoreactivity was originated from endogenous human Gal-1, we finally investigated its expression levels in cardiac tissue (the main target of Chagas' disease). This protein was found to be markedly upregulated in cardiac tissue from patients with severe CCD, compared to cardiac tissue from normal individuals.
The role of C5a in the development of thrombotic glomerulonephritis in rats
Authors: Kondo C , Mizuno M , Nishikawa K , Yuzawa Y , Hotta N , Matsuo S 
Published: March 2003

SUMMARYThrombus formation is the important pathologic finding observed in glomerulonephritis induced by antiglomerular basement membrane (GBM) antibodies. Although strong deposition of C3 and membrane attack complex (MAC) is observed in this disease, the role of complement has not been fully elucidated. The aim of this work was to investigate the role of complement, especially an anaphylatoxin C5a, in a rat model of thrombotic glomerulonephritis. Rats were first pretreated with subclinical dose of lipopolysaccharide (LPS). Thrombotic glomerulonephritis was then induced by intravenous injection with rabbit antirat GBM (RbAGBM) (Group I). For the evaluation of the role of complement, the soluble complement receptor type 1 (sCR1) (Group II) or the C5a receptor antagonist peptide (C5aR-AP) (Group III) was intravenously administered 30 min before RbAGBM injection. For exploring the role of neutrophils, rats were pretreated with cyclophosphamide before induction of disease (Group IV). All rats were sacrificed at 6 h, and histological examination was performed.Rats in Group I developed severe glomerular thrombosis. Leucocyte accumulation and strong binding of C3 and MAC were observed in the glomeruli. In rats treated with sCR1 (Group II) and C5aR-AP (Group III), both leucocyte accumulation and thrombus formation in the glomeruli were significantly inhibited. C3 and MAC were negative in the glomeruli in Group II rats, while they were strongly observed in Group III. In neutrophil depleted rats (Group IV), there was also deposition of C3 and MAC in the glomeruli but thrombus formation was not observed. These findings indicated that glomerular thrombosis is dependent on the leucocytes, and mediated in part by the anaphylatoxin C5a but not MAC in the present model.
Induction and abrogation of LACK reactive cells in the evolution of human leishmaniasis
Authors: Maasho K , Wolday D , Edjigu M , Söderström K , Britton S , Akuffo H 
Published: March 2003

SUMMARYPeripheral blood mononuclear cells (PBMC) from cutaneous leishmaniasis patients with ongoing Leishmania aethiopica infection and individuals cured/under treatment from L. infantum or L. donovani infection were stimulated in vitro with LACK, the Leishmania homologue of receptors for activated C kinase. The LACK protein is conserved in related leishmanial species and is expressed both in the promastigote and amastigote stages of Leishmania. Our results show that LACK induced marked NK and some CD8+ cell proliferation in PBMC from cutaneous leishmaniasis patients with active disease. These responses were coupled with high levels of IFN-γ and IL-10 production. At the concentration tested, the proliferative responses to freeze-thawed Leishmania antigen (Ft-Leish) were higher, while the levels of IFN-γ were consistently lower than that of LACK. Although cells from individuals cured of leishmaniasis could respond to whole Leishmania lysate by proliferation and IFN-γ production, there was no evident response to LACK. Ethiopian controls tested at the same time also showed LACK induced proliferation with IFN-γ and IL-10 responses. Thus LACK reactivity in terms of proliferation and cytokine induction were present in cells from some healthy donors and most of the patients with active lesions, while this response was absent in individuals cured of L. infantum or L. donovani leishmaniasis. Since cure from leishmaniasis often results in life-long protection, and active but not cured patients showed in vitro responses to LACK stimulation, questions arose as to how this highly immunodominant molecule functions during human leishmanisasis. Some possible mechanisms are discussed.
Cytomegalovirus infection and proinflammatory cytokine activation modulate the surface immune determinant expression and immunogenicity of cultured murine extrahepatic bile duct epithelial cells
Authors: Hsu H-Y , Chang M-H , Ni Y-H , Huang S-F 
Published: March 2003

Summary
Murine extrahepatic bile duct epithelial cells (MEBEC) were isolated from extrahepatic bile ducts of BALB/c mice and established in primary culture. The epithelial origin was confirmed by positive cytokeratin 19 staining for these cells and the presence of microvilli and tight junctions under electron microscopy. By immunofluorescent staining with monoclonal antibodies and flow-cytometric analysis, MEBEC in culture constitutively express low levels of intercellular adhesion molecule (ICAM)-1, class I and class II major histocompatibility (MHC) antigens. The expression of ICAM-1 was significantly increased by interferon gamma (INF-γ) or tumour necrosis factor alpha (TNF-α) stimulation. Class I and class II antigen expression were significantly enhanced by INF-γ and in vitro murine cytomegalovirus (MCMV) infection. MEBEC infected with MCMV revealed a progressive cytopathic effect. MEBEC activated by INF-γ or infected by MCMV induced a low but significant proliferation of allogeneic T cells and displayed a significant decrease in the absorbance at O.D. 550 nm in a microtitre tetrazolium assay after these treated cells were co-cultured with allogeneic T cells. These results suggest that following the up-regulation of surface MHC antigen and adhesion molecule expression with cytokines or MCMV, the MEBEC can function as antigen-presenting cells and initiate T-cell proliferation, which in turn trigger the recognition of MEBEC by effector T-cell-mediated cytotoxic responses. These findings may be implicated in the pathogenesis of virally induced, immune-mediated extrahepatic bile duct damage disorders.
Impaired T cell proliferation, increased soluble death-inducing receptors and activation-induced T cell death in patients undergoing haemodialysis
Authors: Ankersmit H J , Deicher R , Moser B , Teufel I , Roth G , Gerlitz S , Itescu S , Wolner E , Boltz-Nitulescu G , Kovarik J 
Published: March 2003

Summary
Haemodialysis is a widespread option for end-stage renal disease (ESRD). Long-term success of dialysis is, however, limited by a high rate of serious bacterial and viral infections. We compared T cell functions in ESRD patients undergoing haemodialysis (n = 20), or were not dialysed and received conventional medical treatment (n = 20). Healthy volunteers (n = 15) served as controls. The T cell phenotype was examined by immunofluorescence using fluorochrome-labelled monoclonal antibodies and FACS analysis. The concentration of soluble CD95/Fas and of tumour necrosis factor-α receptor type 1 (sTNFR1) in the sera was quantified by ELISA. Activation-induced programmed T cell death was triggered by anti-CD3/CD28 antibodies and measured by 7-AAD staining. All immunological tests were performed at least 1 month after dialysis initiation. T cell proliferation in response to phytohaemagglutinin or anti-CD3 monoclonal antibodies was moderately diminished in non-dialysed patients and markedly reduced in haemodialysis patients compared to healthy controls (P &lt; 0·01 and P &lt; 0·001, respectively). In a mixed lymphocyte culture the proliferative response of T cells from dialysed patients was significantly diminished (P &lt; 0·001). T cells of both non-dialysed and dialysed patients have augmented CD95/Fas and CD45RO expression, increased sCD95/Fas and sTNFR1 release and spontaneously undergo apoptosis. Culture of T cells from haemodialysis patients with anti-CD3/CD28 antibodies increased the proportion of CD4+ T cells committing activation-induced cell death by a mean 7·5-fold compared to T-helper cells from non-dialysed patients (P &lt; 0·001). Renal failure and initiation of haemodialysis results in a reduced proliferative T cell response, an aberrant state of T cell activation and heightened susceptibility of CD4+ T cells to activation-induced cell death.
Increased distribution and expression of CD64 on blood polymorphonuclear cells from patients with the systemic inflammatory response syndrome (SIRS)
Authors: Qureshi S S , Lewis S M , Gant V A , Treacher D , Davis B H , Brown K A 
Published: March 2003

SummaryEvidence is growing to suggest that the multiple organ damage of the systemic inflammatory response syndrome (SIRS) arises from the untoward activity of blood polymorphonuclear cells (PMNs), which upon activation acquire the IgG high affinity receptor, CD64. In the current study, flow cytometry was used to assess the prevalence of CD64-bearing PMNs and the intensity of expression of CD64 in whole blood samples from 32 SIRS patients, 11 healthy normal subjects and from eight non-SIRS patients in the intensive care unit (ICU). The percentage of PMNs expressing CD64 was higher in SIRS patients (mean 65%) than in non-SIRS patients (mean 42%; P &lt; 0·02) and in healthy controls (mean 19%; P &lt; 0·001) and was particularly evident in patients with SIRS and sepsis (mean 71%; P &lt; 0·02) as opposed to SIRS alone (mean 55%). There were more CD64 molecules expressed on PMNs from patients with SIRS (median 1331 molecules/cell) in comparison with PMNs from healthy subjects (median 678 molecules/cell; P &lt; 0·01). The highest intensity of CD64 expression was associated with PMNs from patients with both SIRS and sepsis. Functional studies revealed that the supranormal binding of PMNs from patients with SIRS to endothelial monolayers treated with TNFα was impeded by anti-CD64 antibodies (mean 24% inhibition; P &lt; 0·01). Monitoring the distribution of CD64+ PMNs and their level of CD64 expression could be of assistance in the rapid discrimination of patients with SIRS from other ICU patients and in the identification of PMNs which are likely to participate in the pathological manifestations of the disease.