bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glomerular T cells in Heymann nephritis
Authors: Walters G , Wu H , Knight J F 
Published: March 2003

SummaryActive Heymann nephritis (HN) is a rat model of human membranous nephropathy. The appearance of T cells within the glomeruli of HN rats suggests a role for these cells in the pathogenesis of the disease. The aims of this study were to investigate T cells infiltrating the glomerulus in HN in Lewis rats by polymerase chain reaction (PCR) of their Vβ chains, CDR3 spectratyping and sequencing. HN was induced in Lewis rats by immunization with renal tubular antigen (Fx1A) in CFA. Kidneys were collected between 4 and 10 weeks. The glomeruli were separated, homogenized and RNA extracted. RT-PCR, CDR3 spectratyping and sequencing were used to further characterize the infiltrating T cells. Multiple Vβ families showed restriction of their CDR3 spectratypes in each animal. Several TCR Vβ families had identical-sized restricted spectratypes across several different animals. Four Vβ families were sequenced. In three of those four families, the dominant clones showed identical sized CDR3 regions and a striking over-expression of Jβ2.6. Further analysis of the CDR3 regions of the Jβ2.6 clones showed a significant restriction of the amino acids at four of the six CDR3 positions. Glomerular T cells bearing similar CDR3 sequences, using Jβ2.6 and expressing at least two, and possibly more, Vβ genes are involved in the pathogenesis of HN.
Naïve and memory CD4+ T cells and T cell activation markers in HIV-1 infected children on HAART
Authors: Resino S , Navarro J , Bellón J M , Gurbindo D , León J A , Muñoz-Fernández M A 
Published: March 2003

SummaryThe objective of this study was to investigate the relationship between peripheral blood CD4+ T cell subsets and routine viro-immunological markers in vertically HIV-1-infected children undergoing highly active antiretroviral therapy (HAART). CD4+ and CD8+ T cell subsets were examined by three-colour flow cytometry. Plasma viraemia was quantified by a standardized molecular assay. A negative correlation between the %CD4+ T cells and both viral load and the %CD8+ T cells was observed. A strong positive correlation between the %CD4 T cells and naïve, CD38+ and non-activated CD4+ T cell subsets was found, whereas the %CD4 T cells correlated negatively with the numbers of memory, activated and memory-activated CD4+ T cell subsets. Elevated percentages of CD8 T cells were associated with increased memory and CD4+ CD62L-T cell subsets, whereas the naïve and CD4+ HLA-DRCD38+ subsets negatively correlated with the CD8%. Co-expression of CD62L on memory CD4+ cells and high expression of HLA-DR (but not of CD38) were associated with high viral load. No association between viral load and naïve CD4+ T cells was observed. Specific CD4+ T cell subsets may be more informative than routine surrogate markers in defining the evolution of HIV infection and immune reconstitution in children.
Autoantibodies to human cytosol: a marker of sporadic porphyria cutanea tarda
Authors: Ma Y , Fracanzani A L , Sampietro M , Mattioli M , Cheeseman P , Williams R , Mieli-Vergani G , Vergani D , Fargion S 
Published: March 2003

Summary
The enzymes potentially involved in the pathogenesis of sporadic porphyria cutanea tarda (PCT) reside in liver cytosoles and microsomes. PCT is frequently associated with hepatitis C virus (HCV) infection, which is in turn associated with autoimmune manifestations. To investigate whether autoimmune reactions, possibly triggered by HCV, are involved in the pathogenesis of PCT, we measured by immunoblot autoantibodies to human cytosolic and microsomal liver fractions in 82 patients with PCT (77% with HCV infection), 105 with other liver disorders and 40 healthy subjects. Anti-liver cytosolic antibodies were more frequent in PCT patients (38/82, 46%) than in pathological controls (P &lt; 0·05–P &lt; 0·001) or in healthy subjects (3/40, 8%, P &lt; 0·001). Among PCT patients, anticytosolic antibodies were more frequent in HCV positive (36/63, 57%) than in HCV negative (2/19, 11%, P &lt; 0·05) cases. Reactivity to a 40-kDa cytosolic polypeptide was present in 20 PCT patients (19 HCV positive), being more frequent than in all pathological controls (P &lt; 0·01–P &lt; 0·0001). Histological activity index (P = 0·04) and antibodies to HCV (P = 0·027) – but not HCV RNA – were associated independently with anticytosolic antibodies as assessed by multivariate analysis. In contrast, frequency of antiliver microsomal antibodies was similar in PCT patients (24/82, 29%) and pathological controls (8–26%), being higher in the autoimmune hepatitis control group (23/23, 100%, P &lt; 0·0001). In conclusion, anticytosolic antibodies, particularly to a 40-kDa polypeptide, are frequent in PCT and associated with HCV infection and severity of liver damage.
Variations in serum IL-7 and 90K/Mac-2 binding protein (Mac−2 BP) levels analysed in cohorts of HIV-1 patients and correlated with clinical changes following antiretroviral therapy
Authors: Darcissac E C A , Vidal V , De La Tribonniere X , Mouton Y , Bahr G M 
Published: March 2003

SummarySerum levels of interleukin-7 (IL-7), a non-redundant cytokine that plays a crucial role in lymphopoiesis, are known to be elevated in HIV-1-infected subjects. To examine further the association between levels of IL-7, CD4+ cell counts and viraemia, we analysed these parameters in a large cohort of HIV-1 patients along with serum levels of 90K, a marker of disease severity but with no established involvement in lymphopoiesis. While IL-7 levels were only found to correlate with CD4+ cell counts, 90K levels presented strong correlations with both CD4+ cell numbers and with plasma viral loads (VLs). These correlations were maintained in patients naive to treatment with antiretrovirals (n = 38) but were abolished when the analysis was restricted to the group receiving highly active antiretroviral therapy (HAART, n = 82). Moreover, although 90K levels were significantly reduced in patients on HAART, IL-7 levels continued to be elevated despite successful treatment. The influence of HAART on the variations in these serum parameters was further assessed in a longitudinal study on 32 subjects. The HAART-induced decrease in VLs and increase in CD4+ counts were found to correlate with a reduced serum level of 90K and IL-7, respectively. Nevertheless, following a median period of 33 months of immunological and virological successful HAART, serum levels of IL-7 continued to be significantly elevated compared with those detected in healthy controls. These findings suggest that immunotherapy with IL-7, aimed to replenish T-cell stock in HAART-treated subjects, may have a limited impact on the process of immune reconstitution.
Anti-CD38 autoimmunity in patients with chronic autoimmune thyroiditis or Graves' disease
Authors: Antonelli A , Fallahi P , Nesti C , Pupilli C , Marchetti P , Takasawa S , Okamoto H , Ferrannini E 
Published: March 2003

SummaryAutoantibodies directed against human CD38 (an enzyme catalysing the interconversion of NAD+ and cyclic ADP-ribose) have been demonstrated recently in patients with type 2 diabetes. We tested 220 consecutive Caucasian patients with autoimmune chronic thyroiditis, 104 patients with Graves' disease, 220 subjects from the general population (control I) and 78 healthy control subjects not affected by thyroid autoimmune disorders (control II) for the presence of anti-CD38 autoimmunity. Using Western blot analysis and optical densitometry, a specific band corresponding to human recombinant CD38 was identified in the serum of several subjects. By defining anti-CD38 positivity as a standardized optical reading &gt; 3 s.d. higher than the mean value of control I, 10·4% of patients with thyroiditis and 7·7% of Graves' patients were anti-CD38 positive (P = 0·0009 versus 1·8% of control I). Similarly, 13·1% of patients with thyroiditis and 10·5% of Graves' patients had a standardized optical reading &gt; 3 s.d. higher than the mean value of the subjects not affected by thyroid autoimmune disorders (P = 0·002 versus 1·2% of control II). Anti-CD38 autoimmunity did not differ between euthyroid, hyperthyroid or hypothyroid patients or between patients with or without thyroid hypoechogenicity. Anti-CD38 autoantibodies were associated with higher levels of circulating antithyroid-peroxidase antibodies (P = 0·03) and they were more frequent in Graves' patients with ophthalmopathy (P &lt; 0·05). Anti-CD38 autoantibodies are a new autoimmune marker in chronic autoimmune thyroiditis and Graves' disease. The specific role of CD38 and its autoantibodies in the modulation of thyroid cell function or growth remains to be investigated.
Increased expression of pro-inflammatory cytokines and metalloproteinase-1 by TGF-β1 in synovial fibroblasts from rheumatoid arthritis and normal individuals
Authors: CHEON H , YU S -J , YOO D H , CHAE I J , SONG G G , SOHN J 
Published: March 2003

SUMMARYTransforming growth factor (TGF)-β1 is expressed abundantly in the rheumatoid synovium. In this study, the inflammatory effect of TGF-β1 in rheumatoid arthritis (RA) was investigated using cultured fibroblast-like synoviocytes (FLS) from RA and osteoarthritis (OA) patients, as well as non-arthritic individuals. mRNA expressions of IL-1β, tumour necrosis factor (TNF)-α, IL-8, macrophage inflammatory protein (MIP)-1α and metalloproteinase (MMP)-1 were increased in RA and OA FLS by TGF-β1 treatment, but not in non-arthritic FLS. Enhanced protein expression of IL-1β, IL-8 and MMP-1 was also observed in RA FLS. Moreover, TGF-β1 showed a synergistic effect in increasing protein expression of IL-1β and matrix metalloproteinase (MMP)-1 with TNFα and IL-1β, respectively. Biological activity of IL-1 determined by mouse thymocyte proliferation assay was also enhanced by 50% in response to TGF-β1 in the culture supernatant of RA FLS. DNA binding activities of nuclear factor (NF)-κB and activator protein (AP)-1 were shown to increase by TGF-β1 as well. These results suggest that TGF-β1 contributes for the progression of inflammation and joint destruction in RA, and this effect is specific for the arthritic synovial fibroblasts.
Down-regulated donor-specific T-cell reactivity during successful tapering of immunosuppression after kidney transplantation
Authors: VAN BESOUW N M , VAN DER MAST B J , DE KUIPER P , GREGOOR P J H SMAK , VAESSEN LENARD M B , IJZERMANS J N M , VAN GELDER T , WEIMAR W 
Published: March 2003

SUMMARY
Stable cadaveric renal transplant patients were routinely converted from cyclosporin A (CsA) to either azathioprine (AZA) or mycophenolate mofetil (MMF) 1 year after transplantation to reduce the side effects of long-term immunosuppressive therapy. Thereafter, the AZA and MMF dose was gradually tapered to 50% at 2 years after transplantation. We questioned whether a reduction of immunosuppressive treatment results in a rise of donor-specific T-cell reactivity. Before transplantation (no immunosuppression), 1 year (high dose immunosuppression) and 2 years (low dose immunosuppression) after transplantation, the T-cell reactivity of peripheral blood mononuclear cells (PBMC) against donor and third-party spleen cells was tested in mixed lymphocyte cultures (MLC) and against tetanus toxoid (TET) to test the general immune response. We also measured the frequency of donor and third-party reactive helper (HTLpf) and cytotoxic (CTLpf) T-lymphocyte precursors in a limiting dilution assay. Donor-specific responses, calculated by relative responses (RR = donor/third-party reactivity), were determined. Comparing responses after transplantation during high dose immunosuppression with responses before transplantation (no immmunosuppression), the donor-specific MLC-RR (P = 0·04), HTLp-RR (P = 0·04) and CTLp-RR (P = 0·09) decreased, while the TET-reactivity did not change. Comparing the responses during low dose with high dose immunosuppression, no donor- specific differences were found in the MLC-RR, HTLp-RR and CTLp-RR, although TET-reactivity increased considerably (P = 0·0005). We observed a reduction in donor-specific T-cell reactivity in stable patients after renal transplantation during in vivo high dose immunosuppression. Tapering of the immunosuppressive load had no rebound effect on the donor-specific reactivity, while it allowed recovery of the response to nominal antigens.
Granulocyte macrophage colony stimulating factor is elevated in alveolar macrophages from sheep naturally infected with maedi-visna virus and stimulates maedi-visna virus replication in macrophagesin vitro
Authors: ZHANG Z , HARKISS G D , HOPKINS J , WOODALL C J 
Published: March 2003

SUMMARYInfection by maedi-visna virus, a lentivirus of sheep, leads to chronic inflammatory reactions of various tissues. In this report we have analysed the role of specific cytokines in the disease process. A significant increase in expression of interleukin-6, interleukin-10, granulocyte macrophage-colony stimulating factor (GM-CSF) and transforming growth factor-β1 mRNA was observed in alveolar macrophages isolated from the lungs of naturally infected animals when compared with lungs of seronegative controls. Levels of GM-CSF mRNA expression in alveolar macrophages correlated with the presence of lung lesions, but there was no correlation of interleukin-10, interleukin-6, tumour necrosis factor-α and transforming growth factor-β1 mRNA levels in alveolar macrophages from animals with pulmonary lesions. In vitro investigation showed that GM-CSF in the range 0·1–10ng/ml induced a significant increase in viral p25 production after 7 days in acutely infected blood monocyte-derived macrophages. The production of p25 peaked between 7 and 14 days exposure to 10ng/ml of GM-CSF. Quantitative polymerase chain reaction showed that the level of viral DNA in monocyte-derived macrophages was dose-dependent following GM-CSF treatment in the range 0·1–100ng/ml after 7 days. Viral mRNA expression was also enhanced. These findings indicate a role for GM-CSF in the pathogenesis of lymphoid interstitial pneumonia in infected animals.
Up-regulation of MMP-8 and MMP-9 activity in the BALB/c mouse spinal cord correlates with the severity of experimental autoimmune encephalomyelitis
Authors: NYGÅRDAS P T , HINKKANEN A E 
Published: March 2003

SUMMARYInduction of EAE can be inhibited or repressed by administration of soluble metalloproteinase inhibitors. We studied the matrix metalloproteinase (MMP) and their tissue inhibitor (TIMP) expression pattern in experimental autoimmune encephalomyelitis (EAE) of the resistant Th2 prone BALB/c mouse, where the disease can be induced with ultrasound-emulsified antigen/adjuvant (son-ag), but not with conventional technique (syr-ag). We found highly elevated expression of MMP-8 (neutrophil collagenase) mRNA and protein in diseased son-ag challenged mice, colocalizing to neutrophil infiltrates found in brain and extensively in the spinal cord submeningeal space. MMP-8 expression has not been found previously in sensitive mouse strains. The infiltrates stained positive also for MMP-9 protein, and brain homogenates from corresponding mice showed MMP-9 activity during overt disease (days 12–16 post-immunization). TIMP-1 gene expression could be detected in CNS samples from diseased son-ag challenged mice but not in syr-ag or control mice, and the TIMP-1 protein colocalized with GFAP-staining. In contrast, in syr-ag mice both TIMP-2 and TIMP-3 gene expression in the spinal cords was elevated. The results show that sonication, but not extrusion, creates an adjuvant formula potent in activating the matrix metalloproteinase cascade similar to sensitive mouse strains, strongly implicating their role in EAE induction in this Th2 prone strain. The study provides the basis for establishment of MMP-specific therapy in this model.
Simultaneous analysis of T cell clonality and cytokine production in rheumatoid arthritis using three-colour flow cytometry
Authors: BAKAKOS P , PICKARD C , WONG W M , AYRE K R , MADDEN J , FREW A J , HODGES E , CAWLEY M I D , SMITH J L 
Published: March 2003

SUMMARYIn this study we examined the cytokine production by T cells and TCRVβ subsets in peripheral blood (PB) and synovial fluid (SF) from six RA patients and PB from 10 normal subjects, using three-colour flow cytometry. In two RA subjects we assessed T cell clonality by RT PCR using TCRBV family-specific primers and analysed the CDR3 (complementarity determining region 3) length by GeneScan analysis. A high percentage of IFN-γ- and IL-2- producing cells was observed among the PB T cells in both the RA patients and normal controls and among the SF T cells in RA patients. In contrast, the percentage of T cells producing IL-4 and IL-5 was small among PB T cells in both RA patients and normal controls and among SF T cells in RA patients. There was no significant difference in the production of IFN-γ, IL-2 and IL-5 between the two compartments (PB and SF); however, there were significantly more IL-4-producing cells in SF. Molecular analysis revealed clonal expansions of four TCRBV families in SF of two of the RA patients studied: TCRBV6·7, TCRBV13·1 and TCRBV22 in one and TCRBV6·7, TCRBV21·3 and TCRBV22 in the second. These expansions demonstrated cytokine expression profiles that differed from total CD3+ cells, implying that T cell subsets bearing various TCR-Vβ families may have the potential to modulate the immune response in RA patients.
Conserved CDR 3 region of T cell receptor BV gene in lymphocytes from bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis
Authors: SHIMIZUDANI N , MURATA H , KEINO H , KOJO S , NAKAMURA H , MORISHIMA Y , SAKAMOTO T , OHTSUKA M , SEKISAWA K , SUMIDA M , SUMIDA T , MATSUOKA T 
Published: March 2003

SUMMARY
Idiopathic pulmonary fibrosis (IPF) is an inflammatory lung disease characterized by the accumulation of inflammatory cells and deposition of collagen, resulting in lung remodelling. High numbers of T cells are present in bronchoalveolar lavage fluid (BALF) of IPF patients, although the characteristics of these cells are yet to be determined. To elucidate the pathogenic mechanisms of IPF, we analysed the T cell receptor (TCR) of BALF lymphocytes in three patients with IPF and three healthy subjects as control. TCR repertoire of BALF lymphocytes and T cell clonality were examined by family PCR and Southern blot analysis, and single-strand conformation polymorphism (SSCP), respectively. We observed that the TCR repertoire in the lung was heterogeneous, both in the control subjects and three patients with IPF. SSCP analysis demonstrated an increase in the number of accumulated T cell clones in BALF of two of the three patients, but not in the healthy subject. Furthermore, junctional sequence analysis showed the presence of conserved amino acid motifs (ETGRSG, LAxG, QGQ, GxQP, GRxG, VAR, PGT, GTI, GGT, TGR, LxLxQ, SGQ) in the TCR-CDR 3 region of BAL lymphocytes in patients with IPF, whereas only two amino acid motifs (VTTG, GGE) were found in the control. Our findings suggest that T cells in BALF of patients with IPF expand oligoclonally in the lung, suggesting antigen stimulation of these cells.
Preventive effect of sulphated colominic acid on P-selectin-dependent infiltration of macrophages in experimentally induced crescentic glomerulonephritis
Authors: OGAWA D , SHIKATA K , MATSUDA M , OKADA S , WADA J , YAMAGUCHI S , SUZUKI Y , MIYASAKA M , TOJO S , MAKINO H 
Published: March 2003

SUMMARYLeucocytes infiltrate into renal tissue and are involved in the pathogenesis of crescentic glomerulonephritis. The initial event in the process of leucocyte infiltration is characterized by selectin-mediated leucocyte rolling on endothelial surface. Role of selectins in pathogenesis of glomerulonephritis has still been controversial. Sulphated glycolipids and sulphated polysaccharides interfere with the binding of P- and L-selectin with carbohydrate ligands on endothelial cells or on leucocytes. Here we evaluated the role of selectins and the preventive effects of sulphated colominic acid (SCA), a synthetic sulphated polysaccharide, on experimental crescentic glomerulonephritis in Wistar-Kyoto (WKY) rats. Crescentic glomerulonephritis was induced by injection of nephrotoxic serum (NTS) in WKY rats. Rats subsequently received intraperitoneal injection of saline, neutralizing or non-neutralizing monoclonal antibody (mAb) to rat P-selectin and L-selectin, SCA (5 or 10mg/kg/day) or nonsulphated colominic acid (CA) (10mg/kg/day) for 2 weeks. Localization of P-, E-selectin, ligands for L-selectin and intraglomerular leucocytes was examined by immunohistochemistry. Gene expression of platelet-derived growth factor (PDGF) B chain in glomeruli was quantified using real-time RT-PCR. P-selectin was highly expressed on glomerular endothelial cells after injection of NTS, whereas E-selectin and L-selectin ligands were not detected. Anti-P-selectin mAb, but not anti-L-selectin mAb, significantly reduced glomerular infiltration of macrophages, crescent formation, and proteinuria. SCA also reduced proteinuria, macrophage infiltration, and crescent formation in a dose-dependent manner. Furthermore, SCA suppressed gene expression of PDGF B chain in glomeruli. Our results indicate that P-selectin partially mediate glomerular infiltration of macrophage in experimental crescentic glomerulonephritis. Moreover, SCA may inhibit intraglomerular infiltration of macrophages by interfering with P-selectin-dependent adhesion pathway, and progression of experimental crescentic glomerulonephritis.
Antibody responses to the repetitivePlasmodium falciparumantigen Pf332 in humans naturally primed to the parasite
Authors: AHLBORG N , HADDAD D , SIDDIQUE A B , ROUSSILHON C , ROGIER C , TRAPE J F , TROYE-BLOMBERG M , BERZINS K 
Published: March 2003

SUMMARYAntibodies to the degenerate repeats of EB200, a part of the Plasmodium falciparum antigen Pf332, are protective in monkeys. To analyse the prevalence, magnitude and specificity of antibodies to EB200 in malaria-exposed humans, the IgG antibody reactivity with recombinant EB200 protein as well as with crude malaria antigen was determined in Senegalese donors (n = 100; 4–87 years). Antibody reactivity with EB200 was low or absent in children below 15 years but was prevalent and significantly higher in older donors. In comparison, all individuals displayed reactivity with a crude malaria antigen preparation, which also increased with age. The reactivity with the crude malaria antigen was correlated to the reactivity with EB200, suggesting that the low levels of IgG to EB200 found in some adult donors reflected a limited degree of recent exposure to parasites rather than a selective non-responsiveness to Pf332. Comparison of serological and clinical data showed that high levels of antibodies to crude malaria antigen and to EB200 were predictive of fewer future clinical attacks of malaria. A reactivity pattern very similar to that found in Senegalese donors was observed in Liberian adults where 80% of the sera showed reactivity with EB200 and all peptides were recognized by between 60 and 100% of the donors. This strong reactivity with EB200-derived overlapping peptides suggests that the epitopes in EB200, to a large extent, are linear. In the light of previous data on the parasite neutralizing capacity of antibodies to Pf332, the present results emphasize the potential interest of Pf332-derived sequences for inclusion in a subunit vaccine against P. falciparum malaria.