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See detailImmunology in the clinic review series. Focus on type 1 diabetes and virus: enterovirus, thymus and type 1 diabetes pathogenesis
Jaïdane, H.; Sane, F.; Hiar, R. et al

in Clinical & Experimental Immunology (2012), 168

Thymus dysfunction, especially immune suppression, is frequently associated with various virus infections.Whether viruses may disturb the thymus function and play a role in the pathogenesis of autoimmune ... [more ▼]

Thymus dysfunction, especially immune suppression, is frequently associated with various virus infections.Whether viruses may disturb the thymus function and play a role in the pathogenesis of autoimmune diseases is an open issue. Enteroviruses, especially Coxsackievirus B4 (CV-B4), have been largely suggested as potential inducers or aggravating factors of type 1 diabetes (T1D) pathogenesis in genetically predisposed individuals. Several pathogenic mechanisms of enterovirus-induced T1D have been suggested. One of these mechanisms is the impairment of central self-tolerance due to viral infections. Coxsackievirus-B4 is able to infect murine thymus in vitro and in vivo and to infect human thymus in vitro. Thymic epithelial cells and thymocytes are targets of infection with this virus, and several abnormalities, especially disturbance of maturation/differentiation processes, were observed.Altogether, these data suggest that CV-B infection of thymus may be involved in the pathogenesis of T1D. Further investigations are needed to explore this hypothesis. [less ▲]

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See detailInnate lymphocyte and dendritic cell cross-talk: a key factor in the regulation of the immune response.
Reschner, Anca ULg; Hubert, Pascale ULg; Delvenne, Philippe ULg et al

in Clinical & Experimental Immunology (2008), 152(2), 219-26

Dendritic cells (DC) are specialized in the presentation of antigens and the initiation of specific immune responses. They have been involved recently in supporting innate immunity by interacting with ... [more ▼]

Dendritic cells (DC) are specialized in the presentation of antigens and the initiation of specific immune responses. They have been involved recently in supporting innate immunity by interacting with various innate lymphocytes, such as natural killer (NK), NK T or T cell receptor (TCR)-gammadelta cells. The functional links between innate lymphocytes and DC have been investigated widely and different studies demonstrated that reciprocal activations follow on from NK/DC interactions. The cross-talk between innate cells and DC which leads to innate lymphocyte activation and DC maturation was found to be multi-directional, involving not only cell-cell contacts but also soluble factors. The final outcome of these cellular interactions may have a dramatic impact on the quality and strength of the down-stream immune responses, mainly in the context of early responses to tumour cells and infectious agents. Interestingly, DC, NK and TCR-gammadelta cells also share similar functions, such as antigen uptake and presentation, as well as cytotoxic and tumoricidal activity. In addition, NK and NK T cells have the ability to kill DC. This review will focus upon the different aspects of the cross-talk between DC and innate lymphocytes and its key role in all the steps of the immune response. These cellular interactions may be particularly critical in situations where immune surveillance requires efficient early innate responses. [less ▲]

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See detailCytokine production from sputum cells in eosinophilic versus non-eosinophilic asthmatics
Quaedvlieg, Valérie ULg; Henket, Monique ULg; Sele, Jocelyne ULg et al

in Clinical & Experimental Immunology (2006), 143(1), 161-166

The inflammatory pathways involved in asthma are more complex than the sole Th2-mediated eosinophilic airway inflammation. Different phenotypes of asthma have been recently highlighted and are probably ... [more ▼]

The inflammatory pathways involved in asthma are more complex than the sole Th2-mediated eosinophilic airway inflammation. Different phenotypes of asthma have been recently highlighted and are probably underlied by different immunological profiles. The aim of the study was to assess cytokine production from sputum cells in eosinophilic versus non-eosinophilic asthmatics. Induced sputum was obtained from 48 consecutive stable mild to moderate asthmatics (20 eosinophilic asthmatics, 28 non-eosinophilic asthmatics) and 31 healthy subjects. Cytokine released from sputum cells were measured by a home-made two-step sandwich immunoassay. Cytokines investigated were interleukin (IL)-4, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Sputum cells from eosinophilic asthmatics produced more IL-4 than those from both healthy subjects (P < 0.05) and non-eosinophilic asthmatics (P < 0.05). Conversely, sputum cells from eosinophilic asthma were found to release lower amounts of TNF-alpha than those from healthy subjects (P < 0.05). The group of non-eosinophilic asthmatics did not distinguish from healthy subjects with respect to any cytokines measured. Sputum cells from asthmatics exhibiting eosinophilic airway inflammation release more IL-4 and less TNF-alpha than those of healthy subjects. By contrast, non-eosinophilic asthmatics did not distinguish from healthy subjects by abnormal cytokine release from their sputum cells. [less ▲]

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See detailAltered expression of type I insulin-like growth factor receptor in Crohn's disease
El Yafi, F.; Winkler, Rose ULg; Delvenne, Philippe ULg et al

in Clinical & Experimental Immunology (2005), 139(3), 526-533

The fibrotic and antiapoptotic effects of insulin-like growth factors (IGF) are mediated by type I IGF receptor (IGF-1R). IGFs could play a role in intestinal stricturing and in the maintenance of ... [more ▼]

The fibrotic and antiapoptotic effects of insulin-like growth factors (IGF) are mediated by type I IGF receptor (IGF-1R). IGFs could play a role in intestinal stricturing and in the maintenance of inflammation in Crohn's disease (CD). We aimed to describe IGF-1R expression in CD intestinal lesions, to compare it to other intestinal inflammatory diseases and to correlate it with fibrosis and apoptosis. IGF-1R expression and apoptosis (active caspase-3) were studied by immunohistochemistry. Surgical intestinal specimens [17 CD, nine controls, six diverticulitis and four ulcerative colitis (UC)] were used. IGF-1R was expressed transmurally mainly by inflammatory cells (IC) and smooth muscle cells, both in diseased intestine and controls. IGF-1R positive IC were increased in the mucosa and the submucosa of CD (P < 0.007), and in involved areas compared to uninvolved areas (P = 0.03). In UC, the number of IGF-1R positive IC was only increased in the mucosa, and was not different from controls in the submucosa. In diverticulitis, the number of IGF-1R positive IC did not differ from controls. In CD submucosa, IGF-1R expression in IC was inversely correlated with apoptosis in uninvolved areas (P = 0.01). Expression of IGF-1R in submucosal fibroblast-like cells, subserosal adipocytes and hypertrophic nervous plexi was specific for CD. We have shown a transmural altered expression of IGF-1R in CD. This may suggest a role for IGF-1R in the maintenance of chronic inflammation and stricture formation in CD. [less ▲]

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See detailIncreased expression of receptor activator of NF-kappa B ligand (RANKL), its receptor RANK and its decoy receptor osteoprotegerin in the colon of Crohn's disease patients
Franchimont, N.; Reenaers, Catherine ULg; Lambert, Chantal ULg et al

in Clinical & Experimental Immunology (2004), 138(3), 491-498

Crohn's disease (CD) is associated with low bone mass due to chronic inflammation and other factors. Receptor activator of NF-kappaB ligand (RANKL), its receptor RANK and its decoy receptor ... [more ▼]

Crohn's disease (CD) is associated with low bone mass due to chronic inflammation and other factors. Receptor activator of NF-kappaB ligand (RANKL), its receptor RANK and its decoy receptor osteoprotegerin (OPG) are potentially involved in this process as they regulate osteoclastogenesis and are influenced by pro-inflammatory cytokines. The aim of this study was to determine the levels of soluble RANKL (sRANKL), RANK and OPG expression both in the serum and in the colon of CD patients. Levels of sRANKL and OPG were assessed in the serum and the supernatants of cultured colonic biopsies in patients with CD and controls by ELISA. RANK expression was explored by immunostaining and immunofluorescence of fixed colonic samples. OPG and sRANKL levels were higher in the serum of CD patients as compared to age- and sex-matched controls. Levels of sRANKL and OPG were significantly enhanced in cultured colonic biopsies from CD, and OPG levels correlated with histological inflammation, and pro- and anti-inflammatory cytokine levels. No significant correlation was found for sRANKL. RANK(+) cells were increased in the colon of CD, particularly in inflamed areas. These cells were positive for CD68 or S100 protein. We conclude that serum and local levels of sRANKL and OPG are increased in CD. Moreover, RANK is expressed in the colonic mucosa by subpopulations of activated macrophages or dendritic cells at higher levels in CD compared to normal colon. [less ▲]

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See detailIncreased production of matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by inflamed mucosa in inflammatory bowel disease
Louis, Edouard ULg; Ribbens, Clio ULg; Barreto Dos Santos, Amelia ULg et al

in Clinical & Experimental Immunology (2000), 120(2), 241-246

Inflammatory bowel diseases (IBD) are characterized by a sustained inflammatory cascade that gives rise to the release of mediators capable of degrading and modifying bowel wall structure. Our aims were ... [more ▼]

Inflammatory bowel diseases (IBD) are characterized by a sustained inflammatory cascade that gives rise to the release of mediators capable of degrading and modifying bowel wall structure. Our aims were (i) to measure the production of matrix metalloproteinase-3 (MMP-3), and its tissue inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), by inflamed and uninflamed colonic mucosa in IBD, and (ii) to correlate their production with that of proinflammatory cytokines and the anti-inflammatory cytokine, IL-10. Thirty-eight patients with IBD, including 25 with Crohn's disease and 13 with ulcerative colitis, were included. Ten controls were also studied. Biopsies were taken from inflamed and uninflamed regions and inflammation was graded both macroscopically and histologically. Organ cultures were performed for 18 h. Tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-1beta, IL-10, MMP-3 and TIMP-1 concentrations were measured using specific immunoassays. The production of both MMP-3 and the TIMP-1 were either undetectable or below the sensitivity of our immunoassay in the vast majority of uninflamed samples either from controls or from those with Crohn's disease or ulcerative colitis. In inflamed mucosa, the production of these mediators increased significantly both in Crohn's disease (P < 0.01 and 0.001, respectively) and ulcerative colitis (P < 0.001 and 0.001, respectively). Mediator production in both cases was significantly correlated with the production of proinflammatory cytokines and IL-10, as well as with the degree of macroscopic and microscopic inflammation. Inflamed mucosa of both Crohn's disease and ulcerative colitis show increased production of both MMP-3 and its tissue inhibitor, which correlates very well with production of IL-1beta, IL-6, TNF-alpha and IL-10. [less ▲]

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See detailTumour Necrosis Factor (Tnf) Gene Polymorphism in Crohn's Disease (Cd): Influence on Disease Behaviour?
Louis, Edouard ULg; Peeters, Marc; Franchimont, D. et al

in Clinical & Experimental Immunology (2000), 119(1), 64-8

Crohn's disease (CD) is a multifactorial disease with genetic heterogeneity. TNF-alpha plays a key role in the development of the mucosal lesions. The aim of our work was to study a single base pair ... [more ▼]

Crohn's disease (CD) is a multifactorial disease with genetic heterogeneity. TNF-alpha plays a key role in the development of the mucosal lesions. The aim of our work was to study a single base pair polymorphism located in the promoter region of TNF gene, in a large population of CD patients with well defined phenotypes. One hundred and ninety-three patients with CD and 98 ethnically matched controls were studied. The -308 single base pair polymorphism of TNF gene was studied using an allele-specific polymerase chain reaction. Genotype and allelic frequencies were compared between patients and controls and between subgroups of patients defined by sex, age at diagnosis, familial history, location of disease, type of disease, extra-intestinal manifestations, and response to steroid treatment. In 29 patients a measure of TNF-alpha production by colonic biopsies was performed. The frequency of the allele TNF2 as well as the proportion of carriers of the allele TNF2 were slightly but not significantly lower in CD than in controls (11.9% versus 14.8% and 21.5% versus 27.6%, respectively). A more prominent difference in frequencies of allele TNF2 and in proportions of TNF2 carriers was found when comparing subgroups of patients. The frequency of allele TNF2 was significantly higher in steroid-dependent than in non-steroid-dependent disease (28.1% versus 10.3%; Delta = 17.8%, 95% confidence interval (CI) = 6.3-29.5%, P = 0.0027) and tended to be higher in colonic than in small bowel disease and in fistulizing than in stricturing disease. Furthermore, TNF2 carriers tended to be more frequent in patients with steroid-dependent than non-steroid-dependent disease (43.8% versus 19.3%; Delta = 24.5%, 95% CI = 3.6-45.4%, P = 0.022), in patients with fistulizing than stricturing disease (26.5% versus 9.6%; Delta = 16.9%, 95% CI = 1. 1-32.6%, P = 0.036), and in patients with colonic than small bowel disease (26.5% versus 11.1%; Delta = 15.4%, 95% CI = -0.8-31.6%, P = 0.063). Finally, patients carrying at least one copy of allele 2 were found to produce slightly more TNF-alpha at the colonic level. The -308 TNF gene polymorphism may have a slight influence on the behaviour of CD. The carriage of allele 2 may favour steroid-dependent disease and to a lesser extent fistulizing and colonic disease, possibly secondary to a more intense TNF-alpha-driven inflammatory reaction at the mucosal level. [less ▲]

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See detailIncreased synovial fluid levels of soluble CD23 are associated with an erosive status in rheumatoid arthritis (RA).
Ribbens, Clio ULg; Bonnet, V.; Kaiser, Marie-Joëlle ULg et al

in Clinical & Experimental Immunology (2000), 120(1), 194-199

Synovial fluid (SF) levels of soluble CD23 (sCD23) were determined in 96 patients presenting with an inflammatory knee effusion (73 with RA and 23 with reactive arthritis (ReA) serving as a control ... [more ▼]

Synovial fluid (SF) levels of soluble CD23 (sCD23) were determined in 96 patients presenting with an inflammatory knee effusion (73 with RA and 23 with reactive arthritis (ReA) serving as a control inflammatory non-erosive group) and were correlated with the degree of joint destruction, with local immune parameters (IL-1beta, IL-3, IL-4, IL-6, IL-8, IL-10, IL-12 and sCD25) and with serum markers of inflammation, C-reactive protein and erythrocyte sedimentation rate. RA patients, classified as erosive or not according to Larsen's grade, were separated as follows: (i) 13 patients with non-erosive RA; (ii) 16 RA patients with erosions in hands but not in knees, matched for disease duration with the first group; (iii) 44 RA patients with hand and knee erosions, matched with the second group for rheumatoid factor positivity but of longer disease duration. SF sCD23 levels were significantly increased in both erosive RA groups compared with non-erosive diseases, whether RA or ReA (P < 0.05), whose SF levels were not different. SF IL-10 showed a similar profile to that of SF sCD23 and was the only other parameter characteristic of erosive RA, but no direct correlation was found between the two. SF sCD23 was significantly correlated with IL-12 (r = 0.65, P = 0.0001) and sCD25 (r = 0.39, P = 0.0019) exclusively in the two erosive RA populations. In conclusion, these data showing that increased levels of sCD23 are not only found in the SF of erosive joints but also in knee SF of patients with erosive RA but without knee x-ray-diagnosed erosions suggest that this parameter might be of predictive value for joint destruction. Longitudinal studies are however needed to confirm its potential clinical interest. [less ▲]

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See detailCytokine Expression in Squamous Intraepithelial Lesions of the Uterine Cervix: Implications for the Generation of Local Immunosuppression
Giannini, Sandra; Al-Saleh, Walid; Piron, Hélène ULg et al

in Clinical & Experimental Immunology (1998), 113(2), 183-9

We have addressed the notion that the progression of cancer of the uterine cervix is associated with a preferential constraint on the development of a type 1 cellular mediated response, which is necessary ... [more ▼]

We have addressed the notion that the progression of cancer of the uterine cervix is associated with a preferential constraint on the development of a type 1 cellular mediated response, which is necessary to efficiently eliminate (pre)neoplastic cells. Based on the importance of cytokines in the regulation of an appropriate immune response, we have evaluated the expression of IL-12p40, IL-10 and transforming growth factor-beta 1 (TGF-beta1). Using reverse transcriptase-polymerase chain reaction (RT-PCR), the expression of these three cytokines was evaluated in both low-grade (LG) and high-grade (HG) cervical squamous intraepithelial lesions (SIL) and in normal exocervix and transformation zone biopsies. Our results show that the average level of IL-12 increases within both the LG and HG SIL, compared with both control groups. Interestingly, the percentage of HG SIL expressing IL-12p40 was lower compared with LG SIL. In contrast, the expression of IL-10 increased in parallel with the severity of the lesion to a maximal level in HG SIL. Using immunohistochemistry, we ascertained the presence of IL-12 protein in SIL and IL-10 protein in the transformation zone and SIL biopsies. Both IL-12- and IL-10-producing cells were localized in the stroma, not within the SIL. Furthermore, in this study we also observed that the region of the cervix the most sensitive to lesion development, the transformation zone, was associated with higher average levels of the immunosuppressive cytokines IL-10 and TGF-beta1. [less ▲]

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See detailInverse Modulation of Il-10 and Il-12 in the Blood of Women with Preneoplastic Lesions of the Uterine Cervix
Jacobs, Nathalie ULg; Giannini, Sandra L; Doyen, Jean ULg et al

in Clinical & Experimental Immunology (1998), 111(1), 219-24

It has been postulated that an impaired immune response may contribute to the progression of human papillomavirus (HPV)-associated preneoplastic lesions. Based on this hypothesis, we evaluated the ... [more ▼]

It has been postulated that an impaired immune response may contribute to the progression of human papillomavirus (HPV)-associated preneoplastic lesions. Based on this hypothesis, we evaluated the cytokine production in the blood of patients with squamous intraepithelial lesions (SIL) of the uterine cervix. The levels of type-1 (interferon-gamma (IFN-gamma) and IL-12) and type-2(IL-4 and IL-10) cytokines were measured in whole blood culture supernatants of patients with low- and high-grade SIL and control women. There was no difference in IL-4 and IFN-gamma levels between patients with SIL and the control group. In contrast, the ratio of IL-12/IL-10 levels was significantly lower in patients with SIL compared with the control group. A lower IL-12/IL-10 ratio in women with SIL was also observed when peripheral blood mononuclear cell (PBMC) culture supernatants and plasma samples were analysed. In patients, neither the lower expression of the CD3epsilon chain nor the higher frequency of HLA-DRB1*1501 expression could be correlated with abnormal cytokine production. These results suggest that a part of the cytokine network, namely IL-10 and IL-12, is perturbed in patients with SIL. A better knowledge of the role of these cytokines in regulating the growth of HPV-associated SIL might have practical implications for the development of vaccines or immunomodulatory strategies in the treatment of cervical cancers. [less ▲]

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See detailTumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans.
Louis, Edouard ULg; Franchimont, D.; Piron, Anne ULg et al

in Clinical & Experimental Immunology (1998), 113(3), 401-406

TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some ... [more ▼]

TNF-alpha is involved in infectious and immuno-inflammatory diseases. Different individuals may have different capacities for TNF-alpha production. This might determine a predisposition to develop some complications or phenotypes of these diseases. The aims of our study were to assess the inter-individual variability of TNF-alpha production and to correlate this variability to a single base pair polymorphism located at position -308 in TNF gene. We studied 62 healthy individuals. TNF-alpha production after LPS stimulation was evaluated using a whole blood cell culture model. The TNF gene polymorphism was studied by an allele-specific polymerase chain reaction. Other cytokines produced in the culture, soluble CD14 concentrations and expression of CD14 on blood cells were also measured. Among the 62 individuals, 57 were successfully genotyped. There were 41 TNF1 homozygotes and 16 TNF1/TNF2 heterozygotes. TNF-alpha production after LPS stimulation of whole blood cell culture was higher among TNF2 carriers than among TNFI homozygotes (929pg/ml (480-1473pg/ml) versus 521 pg/ ml (178-1307 pg/ml); P<0.05). This difference was even more significant after correction of TNF-alpha production for CD14 expression on blood cells. In conclusion, the single base pair polymorphism at position -308 in the TNF gene may influence TNF-alpha production in healthy individuals. [less ▲]

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See detailBoth Pituitary and Placental Growth Hormone Transcripts Are Expressed in Human Peripheral Blood Mononuclear Cells (Pbmc)
Melen-Lamalle, Laurence ULg; Hennen, Georges ULg; Dullaart, R. P. et al

in Clinical & Experimental Immunology (1997), 110(2), 336-40

The hGH-V gene codes for a variant of human pituitary growth hormone (hGH-N) named placental growth hormone (hPGH). hPGH shares 93% amino acid identity with hGH-N. Until now the hGH-V gene was considered ... [more ▼]

The hGH-V gene codes for a variant of human pituitary growth hormone (hGH-N) named placental growth hormone (hPGH). hPGH shares 93% amino acid identity with hGH-N. Until now the hGH-V gene was considered to be exclusively expressed in human placenta, where it replaces maternal circulating hGH-N at the end of pregnancy. In this study we investigated by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis hGH-N, and hGH-V, gene expression in PBMC in men, women and pregnant women. We have demonstrated that hGH-N and hGH-V transcripts are simultaneously produced by PBMC in both men and women as well as pregnant women. The PBMC of a PIT-1-negative woman expressed only the hGH-V transcript, but not the hGH-N one as expected. In conclusion, hGH-V mRNA is expressed by cells other than the syncytiotrophoblast, is not regulated by PIT-1, and may be involved in immune regulation, as is pituitary GH. [less ▲]

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See detailAutoimmune syndrome after neonatal induction of tolerance to alloantigens: analysis of the role of donor T cells in the induction of autoimmunity
Merino, J.; Schurmans, Stéphane ULg; Wen, L. et al

in Clinical & Experimental Immunology (1990), 79

The injection of (C57BL/6 x BALB/c) F1 spleen cells into BALB/c newborn mice leads to activation of persisting F1 donor B cells and development of a lupus-like syndrome in tolerized BALB/c mice. This ... [more ▼]

The injection of (C57BL/6 x BALB/c) F1 spleen cells into BALB/c newborn mice leads to activation of persisting F1 donor B cells and development of a lupus-like syndrome in tolerized BALB/c mice. This syndrome is characterized by hypergammaglobulinaemia, high levels of anti-DNA and anti-Sm antibodies, circulating immune complexes and deposits of immunoglobulin in renal glomeruli. The role of donor T cells in this model was investigated by injecting the newborn mice with F1 cells depleted in different T cell subsets by using specific monoclonal antibodies (MoAbs). Tolerance, as shown by an absence of H-2b-specific CTL alloreactivity and persistence of immunoglobulin bearing the donor allotype were observed in mice injected with F1 cells previously depleted in the CD4+ and/or CD8+ T cell subsets as well as in those which received Thy-1+-depleted F1 spleen cells. In these mice, a typical autoimmune syndrome was found, including splenomegaly and lymphadenopathy, anti-ssDNA and anti-aortic myosin IgG antibodies and renal deposition of immunoglobulin. However, some quantitative changes were seen: the levels of anti-aortic myosin antibodies were lower in mice tolerized with CD4+-depleted F1 cells than in those receiving untreated F1 cells. Conversely, higher levels of these autoantibodies were observed in mice tolerized with CD8+-depleted F1 cells. These results suggest that mature donor T cells are not necessary neither for the establishment of neonatal tolerance to alloantigens nor for the activation of F1 donor B cells in the production of the autoimmune syndrome in tolerant mice, but they may contribute in the regulation of the expression of autoreactive B cell clones. [less ▲]

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See detailReactivity of human anti-alpha-galactosyl IgG antibody with alpha(1-->3)-linked galactosyl epitopes exposed on basement membranes and on glomerular epithelial cells: an in vitro and in vivo study in the mouse.
Vecchi, M. L.; Davin, J. C.; Castronovo, Vincenzo ULg et al

in Clinical & Experimental Immunology (1989), 78(2), 271-7

Anti-alpha-galactosyl antibody (a-Gal Ab) is a human natural antibody belonging to the IgG class, found in high titres in all normal sera regardless of blood group, and specifically recognizing alpha (1 ... [more ▼]

Anti-alpha-galactosyl antibody (a-Gal Ab) is a human natural antibody belonging to the IgG class, found in high titres in all normal sera regardless of blood group, and specifically recognizing alpha (1-->3)-linked galactosyl residues. We have observed by radioimmunoassay, ELISA, passive haemagglutination and immunofluorescence blocking studies that affinity-purified a-Gal Ab reacted with mouse laminin, but not with the other mouse basement membrane proteins tested; it was able to fix complement in vitro. When injected intravenously into mice, the a-Gal Ab was found to mainly accumulate in kidneys, liver, spleen and lungs. No acute respiratory distress syndrome was observed shortly after the i.v. injection of 100 or 200 microg of antibodies. These doses of a-Gal Ab were also unable to induce acute glomerular injury. However, in primary cultures, the a-Gal Ab (100 or 200 microg per ml of medium) was shown to impair the attachment of mouse glomerular epithelial cells to mouse laminin and to elicit complement-dependent cell damage. The data indicate that the a-Gal Ab can interact in vitro and/or in vivo with alpha (1-->3)-linked galactosyl residues exposed on murine laminin or on murine cultured glomerular epithelial cells. Although this antibody fails to be pathogenic when administered at low doses in the intact animal, similar doses can alter some metabolic properties of these cells in vitro. [less ▲]

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See detailIncreased concanavalin A-binding capacity of immunoglobulin G purified from sera of patients with rheumatoid arthritis
Malaise, Michel ULg; Franchimont, P.; Bouillene, C. et al

in Clinical & Experimental Immunology (1987), 68(3), 543-551

A solid phase radioimmunoassay was set up for direct measurement of the binding capacity of human IgG to three lectins recognizing different carbohydrates of the Fc domain, i.e. peanut agglutinin (PNA ... [more ▼]

A solid phase radioimmunoassay was set up for direct measurement of the binding capacity of human IgG to three lectins recognizing different carbohydrates of the Fc domain, i.e. peanut agglutinin (PNA), Concanavalin A (Con A) and pokeweed mitogen (PWM) which mainly bind to beta-galactose, alpha-mannose and dimers of N-acetyl-beta-glucosamine respectively. The mean specific binding of the 96 normal IgG tested to PNA and to PWM was statistically higher (P less than 0.001) than that to Con A, whereas no significant differences were observed between the mean specific bindings to PNA and to PWM. A statistically significant linear negative correlation could be established only between the relative bindings (expressed in percentage of the total binding to the three lectins) to PNA and to PWM (r = -0.65, P less than 0.001). The mean specific binding of IgG purified from 34 patients suffering from rheumatoid arthritis (RA) to PNA and to Con A was statistically higher (P less than 0.001) than that reached with PWM, whereas no significant differences were noted between their mean binding capacities to PNA and to Con A. When compared to normal IgG, only four out of 34 RA IgG exhibited a significantly higher binding capacity to PNA, whereas all but one RA IgG possessed a significantly higher binding capacity to Con A. Accordingly, the mean specific binding of RA IgG to Con A was significantly higher than that of normal IgG (P less than 0.001). Besides (and contrary to normal IgG), a statistically significant negative linear correlation was noted between the relative bindings of RA IgG to PNA and to Con A (r = -0.89, P less than 0.001). All the five RA IgG tested exhibited an abnormal circular dichroism. Our data suggest that, by altered steric conformation and glycosylation, mannosyl-residues of RA IgG become prominent or terminal or both, and are therefore able to react more effectively with Con A than normal IgG do. [less ▲]

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See detailSpecificity of antibodies to heterologous glomerular and tubular basement membranes in various strains of mice with different H-2 types.
Moulonguet-Doleris, D.; Erard, D.; Auffredou, M. T. et al

in Clinical & Experimental Immunology (1981), 46(1), 35-43

C3H, CBA (H-2k) and NZB (H-2d) mice were immunized with dog insoluble glomerular (GBM) or tubular basement membrane (TBM). The titre of circulating antibodies was sequentially determined and their ... [more ▼]

C3H, CBA (H-2k) and NZB (H-2d) mice were immunized with dog insoluble glomerular (GBM) or tubular basement membrane (TBM). The titre of circulating antibodies was sequentially determined and their specificity was analysed using various soluble antigenic fractions. Glomerular and tubular deposits were studied on serial biopsies by direct immunofluorescence. After elution from whole kidneys, IgG fixation on normal mouse kidney sections was analysed by indirect immunofluorescence. After immunization with insoluble GBM, animals from all three strains develop antibodies mainly directed against collagenous antigenic determinants shared by GBM and TBM. After immunization with insoluble TBM, the antibodies are directed in NZB mice against non-collagenous TBM-specific determinants, in C3H mice against collagenous determinants and in CBA mice against both types of antigenic determinants. Thus the ability to respond to the various antigens of GBM and TBM is genetically determined and does not depend only on the major histocompatibility complex. [less ▲]

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