Evidence for an interleukin 4-inducible immunoglobulin E uptake and transport mechanism in the intestine (original) (raw)
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Le système immunitaire muqueux dans les maladies inflammatoires intestinales
Acta Endoscopica, 1991
Ľimmunité sécrétaire est la partie la mieux définie du système immunitaire muqueux. Ce mécanisme de défense humorale adapté dépend ďune coopération étroite entre ľépithélium sécrétoire et les plasmocytes locaux. Ces immunocytes produisent de préférence des diméres et de plus larges polyméres ďIgA. Les IgA polymériques (poly-IgA) et les pentaméres IgM, contiennent des chaînes J et peuvent pour cette raison, être liés au composant sécrétoire épithélial (CS). Son fonctionnement en tant que récepteur de transport poly-Ig est nécessaire à la production ďIgA sécrétoire (SIgA) et ďIgM sécrétoire (SIgM). Des faits multiples montrent que les anticorps SIgA et SIgM assurent ľexclusion immunitaire, ’opposant ainsi à la colonisation microbienne de la muqueuse et à la pénétration ďantigènes solubles. La production muqueuse de poly-IgA est déréglée de façon significative dans les maladies inflammatoires intestinales (Mil), ce dont témoigne la réduction drastique de ľexpression chaîne-J au niveau des immunocytes IgA muqueux. En outre, on observe une déviation significative des sous-classes IgA2 vers les IgAl, moins résistantes à la dégradation protéolytique. Ces modifications, associées à une activation des lymphocytes T et des macrophages, et à une augmentation importante des cellules productrices ďIgG, altèrent ľhoméostase immunitaire locale et menacent la défense muqueuse. Bien qu’un accroissement de la totalité de la population immunocytaire muqueuse puisse compenser la production relativement réduite de poly-IgA, la diminution de ľexpression CS au niveau de ľépithélium régénératif ou dysplasique, montre que le système SIgA n’est en aucun cas intact dans les Mil. Ľactivation du complément observée en relation avec des dépôts d'IgGl épithéliaux chez les patients atteints de recto-colite ulcéreuse, suggère que ľépithélium de surface est soumis à une agression immunitaire. Ces dépôts épithéliaux contiennent réguliérement des complexes terminaux du complément (CTC) et trés souvent du C3b, témoins ďune activation persistante. La comparaison entre des jumeaux univitellins mais différents du point de vue colite ulcéreuse, suggère qu’une réponse IgGl locale prononcée pourrait, en partie, être génétiquement déterminée ; une possibilité intéressante serait que ce phénomène représente une réponse autoimmune (anti-épithéliale). Néanmoins, ľévénement initial, déclenchant le mécanisme immunopathologique des MII demeure inconnu. La suppression de la tolérance orale aux antigènes endoluminaux a été suggérée comme un mécanisme ďautoentretien possible, probablement par interaction entre les lymphocytes T CD4b+ activés et les cellules épithéliales avec une expression HLA classe II exagérément intense. Secretory immunity is the best defined part of the mucosal immune system. This adaptive humoral defence mechanism depends on a fascinating cooperation between the secretory epithelium and the local plasma cells. These immunocytes produce preferentially dimers and larger polymers of IgA. Such polymeric IgA (poly-IgA), and also pentameric IgM, contain J chain and can therefore become bound to the epithelial secretory component (SC). Its function as a poly-Ig transport receptor is necessary for the generation of secretory IgA (SIgA) and secretory IgM (SIgM). There is abundant evidence that SIgA and SIgM antibodies perform immune exclusion, thereby counteracting microbial colonization and mucosal penetration of soluble antigens. The mucosal poly-IgA production is significantly down-regulated in inflammatory bowel disease (IBD), as revealed by a strikingly decreased J-chain expression in mucosal IgA immunocytes. There is moreover a significant shift from the IgA2 to the IgAl subclass, which is less resistant to proteolytic degradation. These changes, along with activation of T cells and macrophages and a dramatic increase of IgG-producing cells, will alter the local immunological homeostasis and jeopardize mucosal defence. Although the overall increase of the total mucosal immuno- cyte population may compensate for the relatively reduced poly-IgA production, decreased SC expression in regenerat- ing and dysplastic epithelium shows that the SIgA system is by no means intact in IBD. Complement activation observed in relation to epithelial IgGl deposits in
Hepatology, 2007
The liver transport of polymeric IgA (pIgA) from plasma into bile and the immunohistochemical distribution of secretory component (SC) in the liver were studied in dogs, and compared to those in humans, rats, and rabbits. Results were as follows: (i) according to bile and serum protein concentrations and specific activities, plasma pIgA in dogs, like in humans, is transported into bile ~1 0 times more efficiently than albumin, as compared to 320 and 1060 times in rabbits and rats, respectively. (ii) Only ~1 % of an i.v. dose of ['261]pIgA is transported into bile over 8 hr in dogs, like in humans, as compared to -50% over 3 hr in rats and rabbits. These results agree with much smaller daily fractional catabolic rates of intravascular pIgA in dogs (0.28) and humans (0.48) than in rats (24.0). (iii) Total bile IgA contributes daily about 1.5 mg per kg to intestinal pIgA in dogs, a figure similar in humans (0.8 mg per kg) but much smaller than in rats (38 mg per kg) and rabbits (35 mg per kg). (iv) Biliary obstruction in dogs, like in humans, results only in minor and late increases in serum pIgA levels, contrasting with >8-fold increases within 24 hr in rats and rabbits. (v) Unlike in rats and rabbits, SC in dog liver as well as in human liver cannot be detected in hepatocytes although clearly present in bile duct cells. To conclude: (i) major species differences in plasma-to-bile transport of pIgA exist, most probably related to species differences in the ability of hepatocytes to synthetize SC. (ii) Bile duct cells, despite their membranous SC, are much less efficient than hepatocytes to transport pIgA from plasma to bile. (iii) Dogs, but not rats and rabbits, provide a suitable experimental model for further studies on the relationships between the liver and the secretory IgA immune system in humans.
Gastroenterology, 2001
Abbreviations used in this paper: ELISA, enzyme-linked immunosorbent assay; G3PDH, glyceraldehyde-3-phosphate dehydrogenase; HRP, horseradish peroxidase; IEC, intestinal epithelial cell; IL, interleukin; OVA, ovalbumin; PCA, passive cutaneous anaphylaxis; PCR, polymerase chain reaction; RT, reverse-transcription.
The Secretory Immunoglobulin A Response in the Gut
Biochemical Society Transactions, 1977
Humoral immunity manifest in the mammalian gut is often due to the presence there of sIgA (secretory immunoglobulin A) antibodies. A considerable proportion of antibodies of this immunoglobulin isotype are synthesized locally by plasma cells, which are abundant in intestinal lamina propria. B-lymphocyte precursors for IgAsecreting plasma cells ('IgA plasma cells') appear to derive from the Peyer's patches (aggregated lymphatic follicles) of the small intestine. The Peyer's patches of rabbits contain a subpopulation of B-lymphocytes that can repopulate the spleen and lamina propria of irradiated allogeneic recipients with IgA plasma cells (Craig & Cebra, 1971). Pokeweed mitogen stimulates this subpopulation in vitro to generate IgA plasma cells (Jones et al., 1974). The immediate precursors for IgA plasma cells have been isolated in the subpopulation of Peyer's-patch cells bearing membrane Fab, and lacking membrane IgM by fluorescence-activated cell-sorting (Jones et al., 1974; Jones & Cebra, 1974). In addition to supplying precursors for IgA plasma cells, an 'antigen-sampling' role has been ascribed to Peyer's patches (Bockman & Cooper, 1973). Whole protein molecules may pass intact across their specialized dome epithelial cells and arrive in the midst of B-lymphocyte follicles. Thus IgA precursors may have their first encounter with antigen in the Peyer's patches, be stimulated to divide, and migrate in lymph/blood to intestinal lamina propria and generate plasma cells. We have devised an adoptive transfer system to compare the antigen-sensitivity of Peyer's-patch cells with cells from peripheral lymph nodes and spleen (Cebra et al., 1977a,b). Syngeneic or congeneic (CB20+Balb/c) cells were transferred into sublethally irradiated (600rad) recipients which were then challenged 1 day later with 5 x lo8 sheep erythrocytes. Antibody-forming cells in the recipients' spleens were enumerated at various times thereafter by the Jerne plaque assay and by facilitating antisera to distinguish cells making IgM, IgGl, IgG2 and IgA isotopes. Fluorochrome-labelled alloantisera, which distinguished IgA from CB20 (Ig-2*) and Balb/c (Ig-2") congeneic mice, were used to determine the origin of IgA plasma cells in recipient mice. The Peyer's-patch cells were as effective in adoptively transferring IgM and IgG responses as cells from peripheral lymph nodes or spleen. However, only Peyer's-patch cells transferred a significant IgA response, which began at about day 10 after transfer and reached a maximum of IgA Vol. 5
The IgE and IgG subclass responses of mice to four helminth parasites
Cellular Immunology, 1989
To investigate whether the formation of IgE is linked in vivo to an IgG subclass, mice were infected with four helminth parasites, Nippostrongylus brasiliensis (Nbr), Mesocestoides corti, Taenia crassiceps and Trichinella spiralis, and the changes in the serum levels of the different Ig isotypes as well as the antibody response to M. corti and T. crassiceps antigen extracts were determined by radioimmunoassays. All four parasites induced a concomitant increase of the IgE and IgGl serum levels and usually a decrease of the IgG2a level. They also induced an increase of the IgM level but had little effect on the IgGZb, IgG3, and IgA serum levels. The specific antibodies to an M. corti antigen extract were mainly of the IgGl subclass, whereas it was of both IgGl and IgG2a subclasses to T. crassiceps. Injections of dead M. corti induced an increase of all IgG subclasses and similar levels of IgGl and IgG2a anti-parasite antibodies. Subcutaneous instead of intraperitoneal infection with T. crassiceps induced higher IgG2a than IgGl levels and lo-fold lower IgE levels than the natural ip infection; however, despite the greater IgG2a polyclonal response, anti-parasite antibodies were predominantly of the IgGl subclass. The data demonstrate that natural infection with four different helminth parasites induces a concomitant polyclonal IgGl and IgE response. These in vivo observations corroborate the recent in vitro findings demonstrating that interleukin-4 induces lipopolysaccharideactivated murine B cells to secrete both IgGl and IgB, suggesting that the regulation of these two isotypes is linked.
Journal of Immunological Methods, 2000
Currently available methods for the evaluation of antigen-specific immune responses in the intestine, i.e. measurement of IgA in intestinal lavage and antibody secreting cells (ASC) in peripheral blood, are not applicable to large-scale immunogenicity studies or to kinetic studies where repeated sampling is required. Simple and reliable methods need to be developed. Intestinal lavage and faecal samples were collected from 12 mice on days 0, 14, 21, 28 and 35 following initial immunization with four doses of cholera toxin (CT) by the gastric or rectal routes. The concentrations of anti-CT IgA in the faecal extracts showed a high level of correlation with those in the lavage samples (Spearman's correlation coefficient50.85, P,0.0001) regardless of the route of CT administration. Moreover, the kinetics of the immune response as reflected in the faecal extracts mirrored those in the lavage samples regardless of immunization route. As compared to gastric immunization, rectal administration of CT yielded higher levels of anti-CT IgA in both intestinal lavage fluids and in faecal extracts. The use of rectal immunization and the measurement of IgA in faecal extracts for monitoring mucosal immune responses may be relevant for the development of effective enteric vaccines.
European Journal of Immunology, 1999
In pigs the lymphocytes emigrating from the intestinal wall were collected by cannulating the lymphatics, labeled in vitro using a fluorescent dye and retransfused. The injection of 6.6 ± 4.2 × 10 8 cells resulted in a labeling index between 1.5 % in intestinal lymph, 0.2 % in the spleen and lymph nodes,˚0.1 % in the intestinal lamina propria and 0.003 % in intraepithelial lymphocytes. About 25 % of the injected cells were present in the blood and 1 % was recovered in the lymph. T cells were found in similar proportions in the injected and the recovered cells in the organs (70-80 %). The proportion of IgA + cells among the immigrated cells in the intestinal lamina propria ranged from 5 to 8 %, which in absolute numbers was up to 60 % of the injected IgA + cells. T and IgM + cells did not show a higher accumulation in any organ. These experiments in conventional, unrestrained animals revealed that (1) T cells immigrate into the intestinal lamina propria, (2) preferential migration of IgA + cells from gut lymph to the intestinal lamina propria is obvious under in vivo conditions and (3) the immigrated IgA + cells represent a very small population which is difficult to detect when analyzed in relative numbers.
Gastroenterology, 2005
Abbreviations used in this paper: EBV, Epstein Barr virus; EDTA, ethylenediaminetetraacetic acid; ELISA, enzyme-linked immunosorbant assay; FcRn, neonatal immunoglubulin receptor; HRP, horseradish peroxidase; Ig, immunoglobulin; IL, interleukin; OVA, ovalbumin; pIgR, polyimmunoglobulin receptor; RT-PCR, reverse-transcriptase polymerase chain reaction; SCID, severe combined immunodeficiency; Th, T helper.