scholarly journals Maternal IgG immune complexes induce food allergen–specific tolerance in offspring

2017 ◽  
Vol 215 (1) ◽  
pp. 91-113 ◽  
Author(s):  
Asa Ohsaki ◽  
Nicholas Venturelli ◽  
Tess M. Buccigrosso ◽  
Stavroula K. Osganian ◽  
John Lee ◽  
...  
Keyword(s):  
Breast Milk ◽  
Immune Complexes ◽  
Tolerance Induction ◽  
Specific Ige ◽  
Human Breast Milk ◽  
Maternal Supplementation ◽  
Induced Tolerance ◽  
And Control ◽  
Specific Tolerance ◽  
Maternal Igg

The role of maternal immune responses in tolerance induction is poorly understood. To study whether maternal allergen sensitization affects offspring susceptibility to food allergy, we epicutaneously sensitized female mice with ovalbumin (OVA) followed by epicutaneous sensitization and oral challenge of their offspring with OVA. Maternal OVA sensitization prevented food anaphylaxis, OVA-specific IgE production, and intestinal mast cell expansion in offspring. This protection was mediated by neonatal crystallizable fragment receptor (FcRn)–dependent transfer of maternal IgG and OVA immune complexes (IgG-IC) via breast milk and induction of allergen-specific regulatory T (T reg) cells in offspring. Breastfeeding by OVA-sensitized mothers or maternal supplementation with IgG-IC was sufficient to induce neonatal tolerance. FcRn-dependent antigen presentation by CD11c+ dendritic cells (DCs) in offspring was required for oral tolerance. Human breast milk containing OVA-IgG-IC induced tolerance in humanized FcRn mice. Collectively, we demonstrate that interactions of maternal IgG-IC and offspring FcRn are critical for induction of T reg cell responses and control of food-specific tolerance in neonates.

scholarly journals THE THYMUS AND RECOVERY FROM CYCLOPHOSPHAMIDE-INDUCED TOLERANCE TO SHEEP ERYTHROCYTES

1968 ◽  
Vol 128 (1) ◽  
pp. 35-46 ◽  
Author(s):  
Alan C. Aisenberg ◽  
Caroline Davis
Keyword(s):  
Proliferative Response ◽  
Tolerance Induction ◽  
Recovery Process ◽  
Immunological Tolerance ◽  
Base Line ◽  
Drug Injection ◽  
Sheep Erythrocytes ◽  
Lymphoid Depletion ◽  
Induced Tolerance ◽  
Specific Tolerance

Recovery from specific immunological tolerance to sheep erythrocytes induced with the drug cyclophosphamide was studied with the hemolytic plaque technique of Jerne. The base line plaque (19S antibody-forming cell of the unstimulated spleen) and the proliferative response to antigen, both of which had disappeared during tolerance induction, returned with the recovery of specific immunological reactivity. When cyclophosphamide is injected without sheep cells there is temporary immunological unreactivity and lymphoid depletion of the spleen, but specific tolerance is not induced. Recovery is largely complete at the end of 2 wk and does not require the participation of the thymus. When cyclophosphamide is injected together with sheep cells, 18 days after drug injection, tolerance is still complete. In nonthymectomized mice there is rapid recovery during the next 10 wk, followed by much slower restoration over the remaining 20–30 wk of observation. The entire recovery process evidently takes 40–50 wk. In thymectomized CBA mice only minimal recovery takes place in the first 10 wk and no further restoration occurs thereafter. Thymectomy performed 18 days after tolerance is induced, when tolerance is complete, is equally effective in preventing this recovery.

Blockade of Inhibitor Formation by B-Cell Delivered Tolerance to Immunodominant A2 and C2 Domains.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3187-3187
Author(s):  
Tei Chi Lei ◽  
David W. Scott
Keyword(s):  
Immune Response ◽  
B Cell ◽  
Tolerance Induction ◽  
Full Length ◽  
Great Promise ◽  
C2 Domain ◽  
Gene Therapy Protocol ◽  
Inhibitory Antibodies ◽  
Induced Tolerance ◽  
Specific Tolerance

Abstract A major impediment in the treatment of hemophilia is the formation of inhibitory antibodies, which occurs in approximately 25–30% of Hemophilia A patients treated with therapeutic Factor VIII (fVIII). We have focused on the development of a gene therapy protocol for tolerance induction, with an emphasis on the elimination of inhibitor production. Our lab has demonstrated that LPS-stimulated B-cell blasts, transfected with a retrovirus encoding an IgG-peptide fusion protein, such as fVIII domains, are tolerogenic in both normal and primed recipients. Last year, we reported (http://www.abstracts-on-line.com/abstracts/hemphiladelphia03; Scott and Lei 2003) that specific tolerance to the immunodominant epitopes in the C2 domain of fVIII (a major target of inhibitors) could be induced by our protocol. However, the immune response to full length fVIII was only modestly affected. Most inhibitory antibodies are reactive with conformational epitopes on the exposed surfaces of the A2, as well as the C2, domain of fVIII. Therefore, in this study, we inserted residues S2173-Y2332 of the C2 domain and S373-R740 of the A2 domain onto the IgG heavy chain backbone, respectively, to induce tolerance in hemophilic mice. Specific tolerance to each domain was induced by this protocol. Importantly, a combination of A2-IgG and C2-IgG expressing B cells induced tolerance to the full length fVIII molecule, a result which supports the dominance of these domains in the immune response to fVIII. Tolerance was manifested in terms of ELISA, T-cell proliferation and especially Bethesda Unit titers (95% reduction). Similar results were obtained even when treatment was initiated after priming injections of fVIII. In conclusion, this protocol offers great promise for prevention and potential reversal of this serious complication of fVIII replacement therapy. (Supported by HL61883 and a Laboratory Grant from the National Hemophilia Foundation).

Alteration of secretory IgA in human breast milk and stool samples after the intake of a probiotic — report of 2 cases

Open Medicine ◽  
2012 ◽  
Vol 7 (1) ◽  
pp. 25-29 ◽  
Author(s):  
Petar Nikolov ◽  
Marta Baleva
Keyword(s):  
Breast Milk ◽  
Mucosal Immune Response ◽  
Lactobacillus Bulgaricus ◽  
Secretory Iga ◽  
Human Breast Milk ◽  
Human Breast ◽  
Lactating Women ◽  
Before And After ◽  
Stool Samples ◽  
And Control

AbstractOnly a few studies reveal immunological changes in breast milk after the intake of probiotic and none focus on secretory IgA (sIgA). The aim our report was to investigate the levels of sIgA in human breast milk and stools before and after 4 weeks of probiotic intake in a patient with ulcerative colitis (UC) and a control. The study included 2 lactating women: 1 with UC and 1 control. Both received daily 3.75 billion viable Lactobacillus bulgaricus for 28 days. SIgA was measured in breast milk and stools before and after the probiotic intake. The concentration of sIgA in breast milk before the probiotic intake in UC was 408.5 vs 137.4 µg/ml in contol. Fecal sIgA in UC was 420 vs 274 µg/ml in control. After 28 days of probiotic intake there was a decrease in breast milk sIgA in UC but an increase in control — 266.7 vs 914 µg/ml respectively. There was an increase in fecal sIgA both in UC and control — 674.4 vs 1033 µg/ml. It is tempting to speculate that the different sIgA secretion towards the probiotic may be a result of an altered mucosal immune response in UC.

scholarly journals PD-1/PD-L1 Interaction Maintains Allogeneic Immune Tolerance Induced by Administration of Ultraviolet B-Irradiated Immature Dendritic Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-11
Author(s):  
Lanfang Zhang ◽  
Chang-Qing Xia
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Tolerance ◽  
Tolerance Induction ◽  
Ultraviolet B ◽  
Immature Dendritic Cells ◽  
Programmed Death ◽  
Induced Tolerance ◽  
Different Strains ◽  
Specific Tolerance

Our previous study demonstrated that transfusion of ultraviolet B-irradiated immature dendritic cells (UVB-iDCs) induced alloantigen-specific tolerance between two different strains of mice. Programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1) have been suggested to play an important role in maintaining immune tolerance. In the present study, we seek to address whether PD-1/PD-L1 plays a role in the maintenance of UVB-iDC-induced tolerance. We first observe that the UVB-iDC-induced alloantigen-specific tolerance can be maintained for over 6 weeks. Supporting this, at 6 weeks after tolerance induction completion, alloantigen-specific tolerance is still able to be transferred to syngeneic naïve mice through adoptive transfer of CD4+ T cells. Furthermore, skin transplantation study shows that the survival of allogeneic grafts is prolonged in those tolerant recipients. Further studies show that PD-1/PD-L1 interaction is essential for maintaining the induced tolerance as blockade of PD-1/PD-L1 by anti-PD-L1 antibodies largely breaks the tolerance at both cellular and humoral immunological levels. Importantly, we show that PD-1/PD-L1 interaction in tolerant mice is also essential for controlling alloantigen-responding T cells, which have never experienced alloantigens. The above findings suggest that PD-1/PD-L1 plays a crucial role in maintaining immune tolerance induced by UVB-iDCs, as well as in actively controlling effector T cells specific to alloantigens.

Maternal IgG Immune Complexes Induce Food Allergen–Specific Tolerance in Offspring

PEDIATRICS ◽  
2018 ◽  
Vol 142 (Supplement 4) ◽  
pp. S231-S232
Author(s):  
Jessica Galant-Swafford ◽  
Susan Laubach
Keyword(s):  
Immune Complexes ◽  
Food Allergen ◽  
Specific Tolerance ◽  
Maternal Igg

Across The “Sweetiest” Properties Of Human Breast Milk: Focus On Oligosaccharides

2020 ◽  
Vol 16 ◽  
Author(s):  
Flaminia Bardanzellu ◽  
Alessandra Reali ◽  
Maria Antonietta Marcialis ◽  
Vassilios Fanos
Keyword(s):  
Breast Milk ◽  
Active Role ◽  
Individual Variability ◽  
Human Breast Milk ◽  
Formula Milk ◽  
Target Organs ◽  
Lactating Mothers ◽  
Neonatal Nutrition ◽  
Genetic And Environmental Factors ◽  
Systemic Infections

Introduction: Breast Milk (BM), containing nutrients and bioactive components, represents the best source for neonatal nutrition and determines short- and long- term benefits. Human milk oligosaccharides (HMOs) play an active role in these pathophysiological mechanisms. In fact; they influence the shaping of breastfed infant’s gut microbiota, promote intestinal development, confer protection against intestinal or systemic infections modulating immune system; moreover, HMOs determine extra-intestinal effects on several target organs, i.e reducing necrotizing enterocolitis rate or improving brain development. Aims: In this review, we analyze the great inter- and intra-individual variability of BM HMOs, investigating maternal, genetic and environmental factors modulating their composition. Moreover, we provide an update regarding HMOs’ unique properties, underlining their complex interaction with intestinal microbiota and host-derived metabolites. The possible HMOs’ influence on extra-intestinal bacterial communities, potentially influencing newborns’ and even lactating mothers’ health, have been hypothesized. Finally, recognized HMOs’ crucial role, we underline the promising opportunities showed by their addition in formula milk, useful to create dairy products more similar to maternal milk itself.

Organohalogen compounds in human breast milk from Republic of Buryatia, Russia

2007 ◽  
Vol 146 (1) ◽  
pp. 225-232 ◽  
Author(s):  
Oyuna V. Tsydenova ◽  
Agus Sudaryanto ◽  
Natsuko Kajiwara ◽  
Tatsuya Kunisue ◽  
Valeriy B. Batoev ◽  
...  
Keyword(s):  
Breast Milk ◽  
Human Breast Milk ◽  
Human Breast ◽  
Organohalogen Compounds
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