Dataset Information

Antigen-specific regulation of IgE antibodies by non-antigen-specific ?? T cells.

ABSTRACT: We re-examined the observation that ?? T cells, when transferred from mice tolerized to an inhaled conventional Ag, suppress the allergic IgE response to this Ag specifically. Using OVA and hen egg lysozyme in crisscross fashion, we confirmed the Ag-specific IgE-regulatory effect of the ?? T cells. Although only V?4(+) ?? T cells are regulators, the Ag specificity does not stem from specificity of their ?? TCRs. Instead, the V?4(+) ?? T cells failed to respond to either Ag, but rapidly acquired Ag-specific regulatory function in vivo following i.v. injection of non-T cells derived from the spleen of Ag-tolerized mice. This correlated with their in vivo Ag acquisition from i.v. injected Ag-loaded splenic non-T cells, and in vivo transfer of membrane label provided evidence for direct contact between the injected splenic non-T cells and the V?4(+) ?? T cells. Together, our data suggest that Ag itself, when acquired by ?? T cells, directs the specificity of their IgE suppression.

SUBMITTER: Huang Y

PROVIDER: S-EPMC3552125 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Publications

Antigen-specific regulation of IgE antibodies by non-antigen-specific γδ T cells.

Huang Yafei Y Aydintug M Kemal MK Loomis Joshua J Macleod Megan K MK McKee Amy S AS Kirchenbaum Greg G Jakubzick Claudia V CV Kedl Ross M RM Sun Deming D Jacobelli Jordan J O'Brien Rebecca L RL Born Willi K WK

Journal of immunology (Baltimore, Md. : 1950) 20121228 3

We re-examined the observation that γδ T cells, when transferred from mice tolerized to an inhaled conventional Ag, suppress the allergic IgE response to this Ag specifically. Using OVA and hen egg lysozyme in crisscross fashion, we confirmed the Ag-specific IgE-regulatory effect of the γδ T cells. Although only Vγ4(+) γδ T cells are regulators, the Ag specificity does not stem from specificity of their γδ TCRs. Instead, the Vγ4(+) γδ T cells failed to respond to either Ag, but rapidly acquired ...[more]

PMID: 23275606

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Project description:Mast cells and basophils have long been implicated in the pathogenesis of IgE-mediated hypersensitivity reactions. They express the high-affinity IgE receptor, FcϵRI, on their surface. Antigen-induced crosslinking of IgE antibodies bound to that receptor triggers a signaling cascade that results in activation, leading to the release of an array of preformed vasoactive mediators and rapidly synthesized lipids, as well as the de novo production of inflammatory cytokines. In addition to bearing activating receptors like FcεRI, these effector cells of allergy express inhibitory ones including FcγR2b, an IgG Fc receptor with a cytosolic inhibitory motif that activates protein tyrosine phosphatases that suppress IgE-mediated activation. We and others have shown that food allergen-specific IgG antibodies strongly induced during the course of oral immunotherapy (OIT), signal via FcγR2b to suppress IgE-mediated mast cell and basophil activation triggered by food allergen challenge. However, the potential inhibitory effects of IgA antibodies, which are also produced in response to OIT and are present at high levels at mucosal sites, including the intestine where food allergens are encountered, have not been well studied. Here we uncover an inhibitory function for IgA. We observe that IgA binds mouse bone marrow-derived mast cells (BMMCs) and peritoneal mast cells. Binding to BMMCs is dependent on calcium and sialic acid. We also found that IgA antibodies inhibit IgE-mediated mast cell degranulation in an allergen-specific fashion. Antigen-specific IgA inhibits IgE-mediated mast cell activation early in the signaling cascade, suppressing the phosphorylation of Syk, the proximal protein kinase mediating FcεRI signaling, and suppresses mast cell production of cytokines. Furthermore, using basophils from a peanut allergic donor we found that IgA binds to basophils and that activation by exposure to peanuts is effectively suppressed by IgA. We conclude that IgA serves as a regulator of mast cell and basophil degranulation, suggesting a physiologic role for IgA in the maintenance of immune homeostasis at mucosal sites.

Dataset Information

Antigen-specific regulation of IgE antibodies by non-antigen-specific ?? T cells.

Publications

Antigen-specific regulation of IgE antibodies by non-antigen-specific γδ T cells.

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