bluuebunny/crossref_metadata_2025_split huggingface dataset:
Idiotype usage by polyclonally activated B cells in experimental autoimmunity and infection
Authors: SUTMULLER M , BAELDE J J , MADAIO M P , BRUIJN J A , DE HEER E 
Published: March 2003

SUMMARYBoth in animal models and in human systemic lupus erythematosus (SLE) the occurrence of nephritogenic autoantibodies bearing dominant idiotypes has been described. In this study we investigate the relation between the induction pathway of polyclonal B cell activation and the production and glomerular deposition of nephritogenic antibodies with shared dominant idiotype(s). Polyclonal B cell activation was induced in several experimental models characterized by glomerular immune deposit formation. We monitored the occurrence of dominant idiotypes among immunoglobulins deposited in the glomeruli. In addition, we studied the species specificity of the dominant idiotypes, by monitoring their presence in kidney sections of patients with an immunologically mediated kidney disease. Anti-idiotype antisera against two monoclonal anti-DNA autoantibodies were used, derived from MRL-lpr/lpr mice, i.e. clone H241 and clone H130. Autoantibodies with the H241 idiotype were present in immune complex depositions in all experimental models but not in humans. We therefore conclude that the presence of this dominant idiotype is independent of the induction pathway of polyclonal B cell activation. However, autoantibodies bearing the H130 idiotype were only detected in kidney sections of mice with spontaneous lupus.
T cell responses to the putative dominant autoepitope in primary biliary cirrhosis (PBC)
Authors: PALMER J M , DIAMOND A G , YEAMAN S J , BASSENDINE M F , JONES D E J 
Published: March 2003

SUMMARYPBC is characterized by T cell-mediated destruction of the biliary epithelial cells lining the small intrahepatic bile ducts. The E2 and E3 binding protein (E3BP (protein X)) components of pyruvate dehydrogenase complex (PDC) are disease-specific autoantigens in PBC. Attempts to localize the T cell autoepitopes within PDC-E2 have, however, generated contradictory results. One study has suggested the presence of T cell epitopes throughout PDC-E2, whilst another has identified a single dominant 14 amino acid T cell epitope (p163) spanning the lipoic acid binding lysine residue in the inner lipoyl domain (ILD) of PDC-E2. The aim of the current study was to determine the prevalence of T cell responses to p163 and PDC-E2 ILD, and the role played by lipoylation of these antigens in their immunogenicity, in a UK PBC population. We found that the majority of the PBC patients showing a 6-day peripheral blood T cell proliferative response to native human PDC also responded, in a MHC class II-restricted fashion, to biochemically purified PDC-E2 and E3BP (which co-purify) (9/10 positive (SI &gt; 2.76), mean SI 5.74 ± 5.04 (PDC-E2/E3BP) versus 6.67 ± 3.84 (PDC), P = NS), implying that the important PBC-specific T cell epitopes are contained within the PDC-E2 or E3BP components of PDC. Only a minority of patients responsive to PDC, however, responded to either lipoylated recombinant PDC-E2 ILD (4/10 positive, mean SI 1.98 ± 1.24, P &lt; 0.005 versus PDC response) or lipoylated p163 (4/12 positive, mean SI 1.90 ± 1.58, P &lt; 0.001). The lipoylation state did not affect the T cell response to either ILD or p163. Our findings suggest that in some UK patients with PBC there are immunodominant T cell autoepitopes within PDC-E2/E3BP which are outside the ILD of PDC-E2.
Glucocorticoids modulate the development of dendritic cells from blood precursors
Authors: VAN DEN HEUVEL M M , VAN BEEK N M A , BROUG-HOLUB E , POSTMUS P E , HOEFSMIT E C M , BEELEN R H J , KRAAL G 
Published: March 2003

SUMMARYDendritic cells (DC) are professional antigen-presenting cells, capable of priming naive T cell responses. Glucocorticoids (GC) are frequently used in asthmatic patients. In this study we describe the effects of GC on the development and function of monocyte-derived DC (MoDC) in vitro and in vivo. Monocytes from healthy individuals were isolated and incubated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 for 6 days, to induce maturation into MoDC. To study the role of GC on DC differentiation in vitro cells were incubated with dexamethasone at different stages of MoDC development. At day 6 cells were characterized phenotypically by flow cytometry and functionally in an allogeneic mixed leucocyte reaction. To study the effect of GC in vivo patients with mild/moderate atopic asthma were selected. In one group no GC were used, whereas the other group used inhalation GC. MoDC from these patients were generated as described above and tested functionally. Incubation of MoDC or its peripheral blood precursors with dexamethasone decreased the accessory potency dose-dependently. The functional differences could not be explained by the changes in the expression of MHC II and the costimulatory molecules CD40 and CD86. The relevance of this mechanism was confirmed for the in vivo situation as well. MoDC from patients using inhalation GC showed a decreased accessory potency. These data suggest a modulatory effect of GC therapy at the level of the peripheral blood monocyte. The results indicate that GC influence DC development and function in vitro as well as in vivo.
Rapid intestinal ischaemia-reperfusion injury is suppressed in genetically mast cell-deficient Ws/Ws rats
Authors: ANDOH A , KIMURA T , FUKUDA M , ARAKI Y , FUJIYAMA Y , BAMBA T 
Published: March 2003

SUMMARY
Ws/Ws rats have a small deletion of the c-kit gene, and are deficient in both mucosal and connective tissue-type mast cells. In this study, the role of mucosal type mast cells (MMC) in the development of intestinal ischaemia-reperfusion injury was investigated in Ws/Ws rats. Autoperfused segments of the jejunum were exposed to 60 min of ischaemia, followed by reperfusion for various time periods. The epithelial permeability was then assessed by the 51Cr-EDTA clearance rate. In the control (+/+) rats, the maximal increase in mucosal permeability was achieved at 45 min of reperfusion. In contrast, this increase was significantly and potently attenuated in the Ws/Ws rats. Mucosal alkaline phosphatase activity decreased in the control (+/+) rats, but was not altered in the Ws/Ws rats. There were no differences in mucosal myeloperoxidase activity, indicating that granulocytes did not contribute to tissue injury. These results provide direct evidence for the role of mast cells in the pathogenesis of intestinal ischaemia-reperfusion injury.
Surface phenotype analysis of CD16+ monocytes from leukapheresis collections for peripheral blood progenitors
Authors: TANAKA M , HONDA J , IMAMURA Y , SHIRAISHI K , TANAKA K , OIZUMI K 
Published: March 2003

SUMMARY
In peripheral blood progenitor cell (PBPC) collections from patients with solid tumour or haematological malignancy, monocytes were separated into two subpopulations. The majority of monocytes expressed CD14 at a high density without CD16 antigen (the CD14+CD16− monocytes). The remaining monocytes co-expressed CD14 and CD16 (the CD14+CD16+ monocytes). These CD14+CD16+ monocytes amounted to 20.6 ± 15.8%, while those in peripheral blood (PB) obtained from healthy volunteers were 7.3 ± 3.1% (P &lt; 0.05). When subdividing the CD14+CD16+ monocytes into CD14brightCD16dim and CD14dimCD16bright cells, both populations were found to be increased in PBPC collections. Since typical CD14+CD16+ monocytes are the CD14dimCD16bright population, we compared the additional surface antigens on CD14dimCD16bright monocytes with those of CD14+CD16−monocytes. In PBPC collections, the CD14dimCD16bright monocytes exhibited lower levels of CD11b, CD15, CD33 and CD38 expression and higher levels of CD4, CD11a, CD11c and MHC class II, and also revealed a higher percentage of CD4+ cells and a lower percentage of CD15+ cells and CD38+ cells, compared with the CD14+CD16− monocytes. When compared with the CD14dimCD16bright monocytes in PB, those in PBPC collections exhibited higher expression of CD4 and lower expression of CD11b, and also showed higher percentages of CD4+ cells and CD38+ cells and a lower percentage of CD11b+ cells. These results suggest that PBPC collections may be rich in the CD14+CD16+ monocytes in which the proportion of the immature population is increased. It is likely that these monocytes participate in the haematological and immune recovery after PBPC transplantation.
Immunomodulatory effects ofLactobacillus plantarumcolonizing the intestine of gnotobiotic rats
Authors: HERÍAS M V , HESSLE C , TELEMO E , MIDTVEDT T , HANSON L Å , WOLD A E 
Published: March 2003

SUMMARYWe have studied the effect of the probiotic strain Lactobacillus plantarum 299v on the immune functions of gnotobiotic rats. One group of germ-free rats was colonized with the type 1-fimbriated Escherichia coli O6:K13:H1 and another group with the same E. coli strain together with L. plantarum 299v. One and 5 weeks after colonization, bacterial numbers were determined in the contents of the small intestine, caecum and mesenteric lymph nodes. Small intestinal sections were examined for CD8+, CD4+, CD25+ (IL-2R α-chain), IgA+ and MHC class II+ cells and mitogen-induced spleen cell proliferation was determined. Immunoglobulin levels and E. coli-specific antibodies were measured in serum. Rats given L. plantarum in addition to E. coli showed lower counts of E. coli in the small intestine and caecum 1 week after colonization compared with the group colonized with E. coli alone, but similar levels after 5 weeks. Rats colonized with L. plantarum+ E. coli had significantly higher total serum IgA levels and marginally higher IgM and IgA antibody levels against E. coli than those colonized with E. coli alone. They also showed a significantly increased density of CD25+ cells in the lamina propria and displayed a decreased proliferative spleen cell response after stimulation with concanavalin A or E. coli 1 week after colonization. The results indicate that L. plantarum colonization competes with E. coli for intestinal colonization and can influence intestinal and systemic immunity.
Dysregulation of B7.2 (CD86) expression on monocytes of HIV-infected individuals is associated with altered production of IL-2
Authors: KUMAR A , ANGEL J B , AUCOIN S , CREERY W D , DAFTARIAN M P , CAMERON D W , FILION L , DIAZ-MITOMA F 
Published: March 2003

SUMMARY
T helper (Th) responses are mediated in part by immunoregulatory cytokines and the signals delivered by the costimulatory CD28–B7 pathway. In this study, we have investigated the relationship between the regulation of B7 isoform expression on antigen-presenting cells from HIV+ individuals and the production of Th cytokines. The level of expression of both B7.1 and B7.2 isoforms as measured by mean channel fluorescence was significantly decreased on freshly isolated monocytes from HIV+ individuals compared with HIV− controls. However, the levels of expression of B7.1 and B7.2 on both B cells and monocytes increased significantly following culture in HIV+ individuals compared with HIV− controls. B7 expression is subject to regulation by immunoregulatory cytokines. Therefore, we analysed the regulation of B7 expression by cytokines, namely IL-10 and tumour necrosis factor-alpha (TNF-α), the production of which is enhanced in HIV infection and have similar inhibitory effects on B7 expression. Two groups of HIV+ individuals were distinguished on the basis of the inhibitory effect of IL-10 and TNF-α on monocyte B7.2 expression. IL-10 inhibited B7.2 expression on monocytes from some HIV+ individuals (termed responders) like the HIV− controls. However, in a subset of HIV+ individuals (non-responders) this inhibitory effect was lost. Loss of inhibition of B7.2 expression by IL-10 was associated with significantly reduced IL-2 production by phytohaemagglutinin (PHA)- stimulated peripheral blood mononuclear cells (PBMC). These observations showing an association of B7 dysregulation on monocytes and B cells with altered production of IL-2 may have implications in HIV immunopathogenesis.
T cell response pattern to glutamic acid decarboxylase 65 (GAD65) peptides of newly diagnosed type 1 diabetic patients sharing susceptible HLA haplotypes
Authors: RHARBAOUI F , MAYER A , GRANIER C , BOUANANI M , THIVOLET C , PAU B , ORGIAZZI J , MADEC A -M 
Published: March 2003

SUMMARYAutoantibodies and autoreactive T lymphocytes directed against several pancreatic β cell proteins such as GAD65 have been identified in the circulation before and at the onset of clinical type 1 (insulin-dependent) diabetes. Using GAD65 synthetic peptides, we studied the proliferative response of peripheral blood mononuclear cells (PBMC) either from recently diagnosed type 1 diabetic patients, of whom the majority share the disease-associated HLA class II haplotype (DR4-DQB1*0201 or DR3-DQB1*0302), or from HLA-matched control subjects. We found that 67% (14/21) of the type 1 diabetic patients and 39% (9/23) of the control subjects exhibited a positive proliferative response. Compared with control subjects, however, PBMC from diabetic patients proliferated more frequently (P &lt; 0.05) in the presence of peptide pools from the C-terminal region of GAD65 (amino acids 379–585). Diabetic patients with the same HLA-DQ or HLA-DR alleles showed partially identical T cell reactivity, but no clear correlation could be made between MHC class II specificity and T cell epitopes because of multiple combinations of class II alleles. In addition, by flow cytometry, we studied the direct binding of GAD65 peptides to MHC class II molecules of Epstein–Barr virus (EBV)-transformed B (EBV-B) cells obtained from a diabetic patient. We found that 11 GAD peptides were able to bind to the highly susceptible haplotype DRB1*0301/0401-DQA1*0301/0501-DQB1*0302/0201 on the surface of EBV-B cells in partial correlation with the results obtained in the proliferation assays.
Low-density lipoproteins enhance transforming growth factor-beta 1 (TGF-β1) and monocyte chemotactic protein-1 (MCP-1) expression induced by cyclosporin in human mesangial cells
Authors: Di Paolo S , Grandaliano G , Gesualdo L , Ranieri E , Schena F P 
Published: March 2003

SUMMARYCyclosporin (CsA) is widely used in the treatment of renal disease and transplantation, which are often complicated by alterations of lipid metabolism. Both chronic administration of CsA and hyperlipidaemia have been shown to evoke an early macrophage influx and have progressively led to glomerular and interstitial sclerosis. MCP-1 is the major monocyte chemoattractant secreted by stimulated mesangial cells and TGF-β1 is a key mediator of fibrogenesis in chronic progressive renal fibrosis. Thus, the combined effect of CsA and low-density lipoprotein (LDL) on the gene and protein expression of MCP-1 and TGF-β1 in cultured human mesangial cells (HMC) was explored. Both agents induced an early and persistent increase of MCP-1 and TGF-β1 mRNA levels and protein release. The simultaneous addition of CsA and LDL did not display any additive effect on target gene expression, but it caused a synergistic effect on MCP-1 and TGF-β1 protein secretion into culture medium. On the other hand, CsA and LDL had different effects on cell proliferation: the latter increased DNA synthesis, whereas CsA inhibited both spontaneous and mitogen-stimulated mesangial cell growth. The study concludes that CsA and LDL display an additive effect on TGF-β1 and MCP-1 synthesis and release by HMC, thus possibly co-operating to induce an early macrophage influx and the subsequent mesangial expansion and increased extracellular matrix deposition. However, in contrast they seem to modulate HMC proliferation differently, which is a further critical event intimately involved in the development of glomerulosclerosis.
Interferon-gamma (IFN-γ) and prostaglandin E2 (PGE2) regulate differently IL-12 production in human intestinal lamina propria mononuclear cells (LPMC)
Authors: Monteleone G , Parrello T , Monteleone I , Tammaro S , Luzza F , Pallone F 
Published: March 2003

SUMMARYIL-12 modulates Th1 immune response during chronic colitis. Mechanisms regulating IL-12 synthesis in human intestine are poorly understood. The aim of this study was to investigate the effect of IFN-γ and PGE2 on lipopolysaccharide (LPS)-stimulated LPMC IL-12 production. Normal LPMC cultures were run in the presence or absence of IFN-γ and/or PGE2 before LPS stimulation. To examine the role of endogenous PGE2 on LPS-stimulated IL-12 release, LPMC cultures were added of indomethacin before LPS stimulation. IL-12, IL-10 and IL-8 were measured by ELISA. No IL-12 was detected in either unstimulated or LPS-stimulated LPMC cultures. In contrast, LPMC released IL-8 (650 ± 125 pg/ml) and IL-10 (75 ± 25 pg/ml) in response to LPS. Treatment of LPMC with IFN-γ facilitated LPS-stimulated IL-12, whereas it completely abrogated IL-10 production. IL-12 release by LPMC stimulated with IFN-γ and LPS was significantly inhibited by exogenous IL-10. The addition of PGE2 to IFN-γ-treated LPMC cultures inhibited in a dose-dependent manner LPS-induced IL-12 secretion. Furthermore, IL-12 was detectable (85 ± 25 pg/ml) in the supernatants of LPMC cultures treated with indomethacin and LPS. In contrast to the effect on IL-12, PGE2 significantly augmented LPS-stimulated LPMC IL-10 production. However, the inhibition of IL-12 by PGE2 was only partially reversed by anti-IL-10. In a simplified model of LPS tolerance, we finally showed that monocyte-derived macrophages exhibited reduced IL-12 production after repeat LPS stimulation. In these cell cultures, indomethacin abrogated the induction of LPS desensitization. IFN-γ and PGE2 modulate differently the LPMC responsiveness to LPS in terms of IL-12 synthesis.
An African green monkey lacking peripheral CD4 lymphocytes that retains helper T cell activity and coexists with SIVagm
Authors: Murayama Y , Mukai R , Inoue-Murayama M , Yoshikawa Y 
Published: March 2003

SUMMARYNatural infection with simian immunodeficiency virus (SIV) is known to occur in the African green monkey (AGM). The actual onset of the disease has not been recognized in SIVagm infected AGM, and the precise reason for such apathogenicity in the AGM remains unclear. We reported previously that AGM peripheral CD4 lymphocytes underwent a peculiar differentiation from CD4+ to CD4− cells after in vitro activation, and we inferred that the AGM does not fall into a fatal immunodeficient state because of the generation of CD4− helper T cells in vivo. To evaluate this possibility, we examined the relationship between CD4 expression and helper T cell activity in the naturally infected AGM. We identified a healthy monkey almost lacking CD4 T cells in the periphery. This AGM showed no signs and symptoms of immunodeficiency and retained a helper T cell activity in antibody production comparable to those of CD4+ AGMs. In addition, SIVagm could be isolated from CD8+ lymphocytes in the CD4− AGM. These observations suggest that a unique host-virus adaptation has developed in the AGM, and may be helpful in explaining the fundamental reason for the apathogenicity occurring in this monkey.
Two polymorphisms of the tumour necrosis factor gene do not influence survival in pancreatic cancer
Authors: Barber M D , Powell J J , Lynch S F , Gough N J , Fearon K C H , Ross J A 
Published: March 2003

SUMMARY
Polymorphisms of the tumour necrosis factor (TNF) gene have been related to TNF production and outcome in a variety of inflammatory and malignant diseases. Proinflammatory cytokines and the inflammatory state appear to affect outcome in pancreatic cancer. Thus, the present study examined the TNFB and TNF-308 polymorphisms for their relationship to the inflammatory state and survival in pancreatic cancer. Sixty-four patients with advanced pancreatic cancer and 101 healthy subjects were genotyped for each polymorphism. Serum concentrations of the two TNF receptors and C-reactive protein (CRP) were measured in 45 of the cancer patients with no evidence of infection or jaundice, 1 month after surgical intervention. There was no difference in distribution of genotypes between the patient and control groups. There was no association between any genotype and concentrations of any of the measured inflammatory mediators. While those with an elevated CRP concentration had significantly poorer survival, there was no association between either TNF genotype and survival. This study found no association between TNF genotype and the inflammatory state or survival in advanced pancreatic cancer. Other cytokines may be more important than TNF in determining the inflammatory state and disease progress in pancreatic cancer.
Viral load and CD69 molecule expression on freshly isolated and cultured mitogen-stimulated lymphocytes of children with perinatal HIV-1 infection
Authors: De Martino M , Rossi M E , Azzari C , Gelli M G , Chiarelli F , Galli L , Vierucci A 
Published: March 2003

SUMMARY
HIV-1 in adults changes the proportion of mitogen-stimulated lymphocytes expressing the CD69 activation molecule, but little is known about this molecule expression on lymphocytes of HIV-1-infected (HIV-1+) children. Freshly isolated CD3+, CD4+, CD8+ and CD19+ and phytohaemagglutinin (PHA)-stimulated CD3+, CD4+ and CD8+ lymphocytes co-expressing CD69 were investigated cross-sectionally (adopting a MoAb double-staining technique) in 24 HIV-1+ children with severe disease and given anti-retroviral therapy and in 24 age-matched healthy children. CD69 results in HIV-1+ children were correlated with plasma HIV-1 RNA load prospectively determined. HIV-1+ compared with healthy children had higher frequencies of freshly isolated CD3+CD69+ (2.4 ± 2.2% versus 0.9 ± 0.5%; P = 0.002) and CD8+CD69+ (1.5 ± 1.1% versus 0.5 ± 0.2%; P &lt; 0.0001) lymphocytes. The frequencies of CD4+CD69+ and CD19+CD69+ lymphocytes were similar. High viral load correlated with an elevated proportion of freshly isolated CD3+CD69+ and CD8+CD69+ lymphocytes. HIV-1+ children showed reduced frequencies of PHA-stimulated CD3+CD69+ (60.7 ± 7.6% versus 86.1 ± 7.6%; P &lt; 0.001), CD4+CD69+ (73.6 ± 18.2% versus 92.6 ± 5.1%; P &lt; 0.001), and CD8+CD69+ (51.0 ± 19.1% versus 65.3 ± 15.4%; P = 0.007) lymphocytes. Virologic worsening within 6 months correlated with a low proportion of PHA-stimulated CD3+CD69+ and CD8+CD69+ lymphocytes. CD69 molecule expression reflected the coexistence of immune activation and immune deficiency in HIV-1 infection. Changes partly differed from those observed in HIV-1+ adults. CD8+CD69+ (but not CD4+CD69+) lymphocyte proportion correlated with virologic course, and an impaired ability of CD8+ lymphocytes to express CD69 upon PHA stimulation preceded a virologic worsening.